23 ms·

About that Hydroxychloroquine for Covid-19 trial

191 points by hannob 7y ago

vsmhn 7y ago
Also on HN: https://www.sciencemag.org/news/2020/03/who-launches-global-megatrial-four-most-promising-coronavirus-treatments https://www.sciencemag.org/news/2020/03/who-launches-global-... Testing will be randomized apparently.
- ncmncm 7y ago
  Maybe change the link in the header?
deleted 7y ago
[deleted]
bsaul 7y ago
I see many problems with all the caution around that study: 1/ chloroquine is a very well known cheap drug. There is no new risk associated to using it that doctors arent already aware of. 2/ we do have a lot of statistics now on the outcome of patient not treated with that drug. There's no need for establishing a benchmark. Just proper categorization of existing patient should be enough to compare. 3/ people are oversaturating ICU right now. And as such, it is an emergency situation. We should take the reverse reasoning we usually take : if there's no suscipicion this drug could cause new problems, we should have people massively use it whenever possible and look at the result after 6 days (since that's the time the original study says it takes for the first results to show).
- ncmncm 7y ago
  In particular, if it turns out to reduce infection rate, taking it prophylactically will save the lives of everyone who would otherwise die for lack of a ventilator, or who would die even with one. If it does not turn out to reduce infection rate, no harm done. If it turns out to shorten the illness, everyone sick, and also everyone taking it prophylactically who is actually infected but asymptomatic, will reduce their contagion rate by joining the ranks of the non-contagious sooner, reducing everyone's risk. If it does not turn out to shorten the illness, no harm done. Chloroquine is well-known. If it caused an unacceptable rate of liver failure we would already know. I see suggestions that it takes a very high doses to work. But that might be so only for the already severe infections they are using it on. It should be easy enough to discover whether low doses work prophylactically, and safe enough to try them while waiting on results.
  - joe_fishfish 7y ago
    What if it turns out to shorten the illness in 80% of cases but cause liver failure in the other 20%?
    - learc83 7y ago
      It's a well known drug. We already know the side effects.
      - kl4m 7y ago
        Not on people with COVID-19.
    - tyingq 7y ago
      Hydroxychloroquine is significantly less hepatoxic than chloroquine.
- henriquez 7y ago
  Exactly. Since the risks and side-effects are well-established, it’s more ethical at this point to experiment on humans with an “off label” usage. Doctors do that all the time with other meds.
  - _ph_ 7y ago
    Yes, doctors should experiment with the drug and I am certain, a lot of those, who have the necessary conditions to perform a proper experiment, will do. What should not happen now is, that the general public starts taking the drug as a precaution, just because it might work. The known side-effects are too severe (e.g. blindness) and also, there are already shortages of the drug for those who already require it as part of their medical treatment (e.g. immune-supressed).
    - ekianjo 7y ago
      > Blindness This side effect occurs if you take chloroquine for extended periods of time. Look at the data. https://eyewiki.aao.org/Hydroxychloroquine_toxicity https://eyewiki.aao.org/Hydroxychloroquine_toxicity "Risk for toxicity is less with <5.0 mg/kg real weight/day for hydroxychloroquine and <2.3 mg/kg real weight/day for chloroquine[2]. Patients are at low risk during the first 5 years of treatment." And management is as simple as stopping the drug if it starts affecting your vision: "At the first signs of retinal toxicity, hydroxychloroquine should be stopped to prevent further retinal damage and visual loss[2]. "
      - kevingadd 7y ago
        I'd note that the phrase "further retinal damage and visual loss" implies that retinal damage and visual loss has already occurred... how much of that you are willing to tolerate is up to you, I suppose: I'd prefer 0 unless necessary. If the retinal damage is saving me from a death at the hands of COVID-19 maybe it's worth it, but if it's not...
        ekianjo 7y ago
- raverbashing 7y ago
  I have similar thoughts This is not some crazy experimental new drug that was unknown until past week. It's an experimental treatment, it's not an experimental drug, with unknown side effects. For a condition where time is critical. Of course, we should also be quick to discard unpromising drugs, and not only focus on one promising drug. WHO is starting a megratrial of several drugs now https://www.sciencemag.org/news/2020/03/who-launches-global-megatrial-four-most-promising-coronavirus-treatments https://www.sciencemag.org/news/2020/03/who-launches-global-... (including CQ/HCQ)
- jonathanstrange 7y ago
  This is irresponsible. This drug has severe side effects, it makes absolutely no sense to prescribe it for a completely different disease without first confirming in clinical trials that it has positive effects. > if there's no suscipicion this drug could cause new problems, we should have people massively use it That's not how evidence-based medicine works. The drug is known to cause new problems because of the side effects. Clinical trials are needed to determine whether these are outweighed in patients by positive health effects. You do not prescribe medicine on the basis of hunches.
  - _red 7y ago
    You are currently running another experiment called: Crash the global economy. That's also irresponsible. Should 10-yr olds be forced to give their life to save 85 yr olds?
    - JoeAltmaier 7y ago
      Maybe a bit of strawman there. With more information (hopefully coming) we should be able to make more nuanced decisions.
  - ekianjo 7y ago
    > This is irresponsible. This drug has severe side effects What are you talking about? The severe side effects are known and are usually associated with chronic usage of that drug. Chloroquine is taken for prophylaxis against malaria (daily) in many places in the southern hemisphere. Usual regimen is at least for 8 continuous weeks! EDIT: Toxicity here: as you can see it's very well tolerated. https://eyewiki.aao.org/Hydroxychloroquine_toxicity https://eyewiki.aao.org/Hydroxychloroquine_toxicity
    - jonathanstrange 7y ago
      The suggestion on the table is to give this drug to extremely ill patients who suffer from a new viral disease on the basis of anecdotal evidence and without clinical trials. The suggestion was to massively prescribe it. What health authorities want to do is to allow physicians to use the drug if the patient agrees, but only in a controlled setting in which data is collected and there is a control group. So at least afterwards we could draw conclusions about whether it killed more people or helped saving people. Does that not make sense to you?
- hannob 7y ago
  Opinions like this seem to be popular these days, but they're dangerous. Because this is an emergency we want reliable information. Think about it like this: If these researchers had done a proper trial - and there's absolutely no reason to think that they couldn't have done that in the same amount of time with the same amount of effort - then we'd actually know something useful now. With that trial - we don't.
  - throwaway_pdp09 7y ago
    Agreed, this kind of thinking comes from fear and desperation (and another kind is denial of reality - this can't be happening so it isn't. My neighbours still don't realise it's actually happening). If we want to deal with covid we should have started years ago. As ever, we didn't.
  - hanniabu 7y ago
    > Because this is an emergency we want reliable information. So much for that given the president was recommending chloroquine to be used off the cuff.
  - pbreit 7y ago
    "no reason to think that they couldn't have done that in the same amount of time with the same amount of effort" There is EVERY reason to think they were not in a position to a "proper" test. They are in the middle of an epidemic!
  - ping_pong 7y ago
    They are in a war zone in Italy and presumably in the US very soon. If hydroxychloroquine is safe (except for some people with a known predisposed genetic condition), then we should be giving it widely and early. We can worry about the science and studies later on, but right now we need to save lives and decrease ICU overload.
  - tim333 7y ago
    This was done in about a week. Where's an example of a clinical trial to your liking done that quickly?
- httpsterio 7y ago
  Being sick with a disease like Covid-19 could absolutely alter how a medication works on a person. The drug might be safe to a person with a certain profile and it has been tested against those, but each underlying issue is a new profile which it should be tested against as separately as possible.
  - guiriduro 7y ago
    I think this is the fairest counter-argument I've heard so far about safety of HCQ in Covid-19. I still think the background of "you're in a house burning down, some tests tentatively indicate this may be effective..." weigh more against the risk of side-effects or worse progression due to CQ/HCQ. We ought to be able to devise some experiments to add certainty, using mainly retrospective data now available. Most SLE/Lupus patients take HCQ, and reportedly none in the cohort of the doctor I know have sufficiently severe symptoms to qualify for pCR testing to even establish if they have Covid19. This is Spain with (currently) 708 cases per MM. Of course, caveats like absence of evidence is not (necessarily sufficient) evidence of absence. It may be that SLE or other immuno-modulation treatments have some effect - someone should do analysis with matched non-SLE HCQ and non-HCQ prophylaxis cohorts. But back to my main point with the house burning metaphor for exponential infection - the risk landscape demands we take more risk, give HCQ widely instead of waiting for the conclusion of prospective studies. We can withdraw it if it is shown to be no better than placebo or worsens outcomes when enough data is available to conclude.
  - dcolkitt 7y ago
    Based on that reasoning, we shouldn't give any pharmaceuticals to coronavirus patients. Even simple fever relievers, like acetaminophen, or oral rehydration fluids should be prohibited because we just don't have enough data to know how they'll interact with COVID-19 specifically.
- lultimouomo 7y ago
  > 3/ people are oversaturating ICU right now. And as such, it is an emergency situation. From what I can gather chloroquine is already used as a first line treatment in Italian hospitals (at least it is indicated as such by the COVID treatment guidelines published by the society of Italian infectious disease specialists [0], and has been for quite some time - this document is from 10 days ago, but an earlier revision was not different regarding chloroquine). If this is the case, it's pretty clear that this is no miracle cure - it has at best a marginal effect. [0] http://www.simit.org/medias/1569-covid19-vademecum-13-03-202.pdf http://www.simit.org/medias/1569-covid19-vademecum-13-03-202...
  - raverbashing 7y ago
    Thanks for this reference, it seems they are proposing 2 potential treatments (p. 13) for the more severe patients > Il trattamento deve essere accompagnato da trattamento antivirale (lopinavir/ritonavir o remdesivir + clorochina/idrossiclorochina) e/o steorideo (desametasone) This is from the 13th of March so I guess there will be still some days until we see results of this (either positive or negative)
    - dcolkitt 7y ago
      For the record since that decision day, the growth rate in the number of deaths in Italy has fallen in half[1]. In the 9 days from March 13 to March 22 the daily number of deaths grew 160% from 250 to 651. Prior to that, the same level of growth occurred in 4 days between March 9 (96 deaths) to March 13. That seems like pretty strong evidence that the new treatment protocol is drastically decelerating the pandemic in Italy. [1]https://www.worldometers.info/coronavirus/country/italy/ https://www.worldometers.info/coronavirus/country/italy/
      - lultimouomo 7y ago
        This does not make much sense to me. If it was effective, it should decrease the lethality rate, not the growth in the number of deaths which is much more affected by the actual number of cases. In the page you link you can see that lethality rate has not fallen. Also, as I wrote I'm pretty sure that I saw an earlier version of that document, dating IIRC to the beginning of the month, that prescribed more or less the same combination of chloroquine and antivirals as a first line treatment.
- jpz 7y ago
  It isn't vitamin C. It has a lot of side effects, including serious psychiatric ones in limited cases. If you give it to 100 people you're going to get new health issues that you didn't have before in that population.
  - jansan 7y ago
    Interestingly there is a trial to use a high dose of vitamin C to treat COVID-19 ARDS: https://youtu.be/bt-BzEve46Y?t=2107 https://youtu.be/bt-BzEve46Y?t=2107
- kingkawn 7y ago
  You cannot pour a drug into the populace that will cause side effects on a mass scale that might also overwhelm the healthcare system. It is nice to imagine we have the medicine already, that we can simply wave our hands distribute the pills and everything can go on as it was before this. But we do not and can not go back.
- wpietri 7y ago
  This is absurd: > There is no new risk associated to using it that doctors arent already aware of. You're imagining that their might be an unknown benefit using it with a novel disease, but you're confident that there won't be unknown risks? Drugs just have effects. Risk/benefit is a human construction we apply over the top. There's no reason to expect only good surprises here.
  - tim333 7y ago
    Though why should it have weird side effects when used for COVID that it didn't when used for malaria?
    - wpietri 7y ago
      As I said, drugs just have effects. Humans then look at the results, decide which are good and bad, and then label the bad ones "side effect". So I think the real question is: why do you think 100% of the novel effects will be later put in the "good" bucket?
- m0zg 7y ago
  Yeah, it's important to have it available if it's needed and it's important to conduct at least some sort of trial. Because the drug, combined with azithromycin is so fast acting, we should see the first results in a few days. Worst thing that can happen is it doesn't work. Best thing that can happen is we can save 1.8 trillion dollars and restart the economy. Under these circumstances one would be an idiot not to give it a try. Coughing your lungs out but feel like CNN is not lying to you? Easy! Refuse the drug. Nobody can force you to take it.
  - DanBC 7y ago
    > Worst thing that can happen is it doesn't work. Worst thing that can happen with a chloroquine and azithromycin combination is that it causes heart arrhythmia and sudden death in a patient that would not have otherwise died. Studies of patients taking this combination of meds include daily EKGs, which is something the general population at home isn't going to have access to. https://twitter.com/search?q=azithromycin%20qt&src=typed_query https://twitter.com/search?q=azithromycin%20qt&src=typed_que...
    - m0zg 7y ago
      That's why they are starting with a trial, and not a full scale roll out. Other countries are using this combination of drug, and it's not because they're huge fans of Trump, I can assure you. We also have literally millions of devices out there capable of detecting arrhythmia - they're called Apple Watch.
      - snegu 7y ago
        Apple Watch can't detect long QT, which is one of the risk factors here.
        m0zg 7y ago
        That's like saying construction N95 masks can't be used in the medical setting just because they lack appropriate certification. That old shibboleth has been defenestrated weeks ago. I bet it can, if FDA is beat over the head with a shovel, which it will be if the need arises. It's a real ECG verifiably capable of detecting irregular hearth rhythm, and it costs a tiny fraction of what a big-ass ECG machine would, and therefore can be deployed at a much larger scale. Just because it could only get approval to detect atrial fibrillation duing "peacetime" doesn't mean it can't be pressed into service for other things.
- gus_massa 7y ago
  > There's no need for establishing a benchmark. Just proper categorization of existing patient should be enough to compare. This is very difficult to do. In this study all the patients in the treatment group are from a hospital and most of the patients in the other hospital are from other hospital. Do the population of both hospitals have the same median income? Usually a low income cause a bad diet that may cause bad health that has a worse prognosis. Are the patients in the other countries classified by income? Does the difference in income cause more/less consumption of milk? Bottled milk has an additional amount of vitamin D, and some unconfirmed reports say that the lack of vitamin D is bad for covid19. Does this difference depend on the country? For historical/genetic reason, French drink more milk that Chinese. What about wine, is the consumption of wine important? What is the effect of temperature and humidity in the no-hydroxychloroquine group? The average climate conditions change from country to country and from place to place and from month to month. To be included in the testing group the patient must give consent. Probably they have not to be too wasted to be able to read it. Probably not been to wasted is a good sign. There are a lot of factors, and not all of them are known, not all of them are easy to measure, not all of them are measured. So you need a control group.
- rsynnott 7y ago
  > chloroquine is a very well known cheap drug. There is no new risk associated to using it that doctors arent already aware of. I mean, you could say the same of practically any older drug. It's a fairly well-understood, cheap, somewhat dangerous drug. > we do have a lot of statistics now on the outcome of patient not treated with that drug. Sure. We also have a lot of statistics on the outcome of patients not treated with thalidomide, and morphine, and basically any other cheap somewhat dangerous drug you care to mention. > if there's no suscipicion this drug could cause new problems While I don't think there are, there's the certainty that it will cause the usual old problems that this drug causes. Which you probably don't want when you also have covid-19. We'd be better off waiting on a proper trial.
  - TheHypnotist 7y ago
    We know the side effects for a healthy individual or those with malaria, but how do we know for certain this won't cause new problems in those with COVID-19?
- mrfusion 7y ago
  You’re absolutely right. We need to act fast.
- jcrubino 7y ago
  2) It complicates the treatment of the patients who will experience the worst cases of COVID-19 causing panic... people above 65 with diabetes and heart conditions. 3) Again this drug has well known precautions that reads like the all the people who will experience the worst of COVID-19 Having Grandpa John walk in for COVID-19 and roll out for death by QT elongation is not something the public will have to litigate.
  - dcolkitt 7y ago
    > Again this drug has well known precautions that reads like the all the people who will experience the worst of COVID-19 Except those precautions are at least two orders of magnitude less than the case fatality rate for coronavirus infection. Equivalently, there are scenarios where a seatbelt can decapitate you or trap you in a drowning car. But you'd still be a fool to drive without one, because buckling is a thousand times more likely to save you than kill you.
    - jcrubino 7y ago
      You missed the point. The most serious cases of COVID-19 affect all the people who have the underlying conditions that have precautions listed using H-Chloroquine. That makes the normal ICU case of COVID-19 more difficult (time consuming) to manage because now you have to spend time managing / monitoring: The condition, COVID-19, the side effects of H-Chloroquine on vital body systems already impaired, already being attacked by COVID. Throw the magnitude two out the window like a lucky car crash victim while these patients suffer the crash in the hospital. Not even Bernie was going to pay for the specialty concierge care needed to manage such a patient and yet you some how assume that is how it works.
- epistasis 7y ago
  > we do have a lot of statistics now on the outcome of patient not treated with that drug. There's no need for establishing a benchmark. Just proper categorization of existing patient should be enough to compare. This is very wrong; we have good aggregate statistics across lots of different hospitals, but for a study with a small number of sites where the patients are treated with the drug, there's enough inter-site variability that may obscure any effect, or create a false effect. This is doubly true as health care varies as sites get overwhelmed, and healthcare workers get increasingly strained from long shifts. There will be far more variability as time goes on. And for how small we expect the effect to be, based on the data in the paper, we really should include controls. All that said, I think that the publication of this flawed study is very good, and why pop-science takes that excoriate science as "most research finding are false" really communicate the wrong way to think about science, and limit its applicability. Flawed datasets like this still give us clues, and publishing flawed data is still useful to others to accelerate the pace of science. Which is why we need to take the attitude that publications are point in time guesses at what's going on, and only rarely does one come out that can be considered on its own as definitive, and that it's good to have mostly "here's some data and analysis but we don't have a complete theory yet"-type-papers. Without those intermediate publications, science would grind to a halt.
  - dcolkitt 7y ago
    > but for a study with a small number of sites where the patients are treated with the drug, there's enough inter-site variability that may obscure any effect, or create a false effect. The simple solution is to spread it over enough sites so that the law of large numbers quantifies that variability into the dataset. For example if we run trials over 10 hospitals in 20 different states, 200 sites in the dataset would almost certainly capture inter-site variance.
    - akiselev 7y ago
      That only normalizes natural variances in your patients, not artificial biases introduced by the healthcare system. Pump and other hardware measuring out dosages might come from different manufacturers or be calibrated and serviced by different technicians. Maybe the study includes one too many hospitals in a region dominated by one manufacturer whose hardware tends to error more in one direction than other manufacturers. The generics used by pharmacies and hospitals might be slightly different because of local relationships. Exercise, ability to have visitation in quarantine, and other amenities in hospitals will have differing impacts on confounding factors like exercise and morale. And on and on. There are a bunch of "contract research organizations" all over the world, quite a few of them making billions of dollars a year, who specialize only in running clinical trials because these things are so complicated. The documentation for clinical trials are often thousands of pages long describing tiny details like device calibration across hospitals trying to eliminate as many risks as possible. These organizations tend to have long standing relationships with hospitals and host many different trials in each one with a bunch more subcontractors who do patient selection.
- herf 7y ago
  Check PDR before you say things like this: https://www.pdr.net/drug-summary/Plaquenil-hydroxychloroquine-sulfate-1911.7193 https://www.pdr.net/drug-summary/Plaquenil-hydroxychloroquin... Has side effects in patients with G6PD deficiency (10-15% in some populations) Cardiotoxicity, retinopathy, and these are especially likely in older patients. https://www.bloomberg.com/news/articles/2020-03-20/virus-drug-touted-by-trump-musk-can-kill-with-just-two-grams https://www.bloomberg.com/news/articles/2020-03-20/virus-dru... Disclaimer: am not a MD or public health person, but I talk to both.
- aaavl2821 7y ago
  Many doctors are already actively prescrbign this. I heard that it is basically de facto standard of care in France. Doctors recognize that when eveidence based medicine doesn't provide an adequate treatment, they need to improvise. Off-label prescribing is very common The point of these studies is to help the evidence catch up to improvised clinical practice. If the studies are poorly designed, that goal is not achieved
- eagsalazar2 7y ago
  I imagine some country/region out there will adopt this approach so we'll all get to find out in a few weeks (possibly at their expense).
  - jansan 7y ago
    It is being used in several countries already (US and Europe, not sure about Asia). If you are interested in details, here is a video of a conference call at UCSF: https://youtu.be/bt-BzEve46Y?t=3194 https://youtu.be/bt-BzEve46Y?t=3194
- IAmEveryone 7y ago
  Your second and third point are completely independent of the substance at issue. So by that logic, we should test everything that is “safe”. Prayer? Meditation? Garlic? Red wine? Cannabis?
  - perl4ever 7y ago
    https://en.wikipedia.org/wiki/Generally_recognized_as_safe https://en.wikipedia.org/wiki/Generally_recognized_as_safe ...I mean it is a big loophole. Something I've wondered about for years is V-8 juice. Seems healthy, but what about the psoralens in celery? I'm not saying that everything does need to be tested, but if you don't, you don't really know and no mental gymnastics can change that.
- naasking 7y ago
  > There is no new risk associated to using it that doctors arent already aware of. You can't possibly know whether this drug would have adverse interactions with a new illness.
Cantbekhan 7y ago
If you are curious, this is the actual Chinese trial registration (edit: not results) about hydroxichloroquine (among the many citations in the pdf) http://www.chictr.org.cn/showprojen.aspx?proj=48880 http://www.chictr.org.cn/showprojen.aspx?proj=48880
- hannob 7y ago
  Just to make this clear: This is a trial registration, not a result.
- chvid 7y ago
  Is this an ongoing trial? When are the results due? 3x100 subjects (is that correctly read?) seems quite powerful.
  - Cantbekhan 7y ago
    Yes it seems they have 100 on one dosage, 100 one a different dosage and 100 in a placebo group. According to the register, the study execution time should be "2020-01-31 To 2020-02-29" But nobody seems to have any insight on the final results. But I would recommend this article with comments of the study leader (Dr Zhang Zhan). The article also explains how they initially discovered the efficiency of the drug by just noticing there were no lupus patients (who were under chronic treatment of hydroxichloroquine) infected with covid19. https://www.jqknews.com/news/388543-The_novel_coronavirus_pneumonia_has_short_term_curative_effect_on_the_treatment_of_new_crown_pneumonia.html https://www.jqknews.com/news/388543-The_novel_coronavirus_pn...
    - hanniabu 7y ago
      > But nobody seems to have any insight on the final results. I assume that means it's either too small of a sample size or it doesn't make enough of an affect?
      - zeckalpha 7y ago
        A study designed like this shouldn’t have data analysis before it is all collected.
sanxiyn 7y ago
Favipiravir trial result is out and the result looks good: https://www.medrxiv.org/content/10.1101/2020.03.17.20037432v1 https://www.medrxiv.org/content/10.1101/2020.03.17.20037432v...
- ncmncm 7y ago
  There has also been success with Avastin (bevacizumab), although the WHO does not seem to be pursuing it. https://clinicaltrials.gov/ct2/show/NCT04275414 https://clinicaltrials.gov/ct2/show/NCT04275414
  - adrianN 7y ago
    Since it ends in mab I assume it's a monoclonal antibody. Those are expensive as fuck because they're so difficult to make. I wonder whether we could scale production up to meet pandemic demand.
    - hprotagonist 7y ago
      mabs are not a straight small molecule synth. Scale as much as you want, growing them takes a while even in parallel. (this is more or less also why vaccine timelines are so long; chicken eggs take a bit of time to get going, and that's the best breeding ground we have!)
- deskamess 7y ago
  The world needs something that is accessible. "As of 23 March 2020, it seems that Japan and China have issued an export ban on the substance. Japan and China are the only countries in which favirapir is produced and approved as a medical compound." [1] [1] https://en.wikipedia.org/wiki/Favipiravir https://en.wikipedia.org/wiki/Favipiravir
  - dx034 7y ago
    And I guess setting up factories to produce millions of doses of new meds can take a while. At the same time, each new manufacturer has to negotiate terms with the patent holder. Using an existing cheap generic drug means that production facilities are already up and running and that any company could start if they have the means to produce it. Apparently a 1-month dose costs £5 in the UK, so there doesn't seem to be a large hurdle to produce it.
emilsedgh 7y ago
I have 0 clues about clinical trials and the procedures. My questions is: Why are so few studies done on this? I think so far we have 2 studies. (from China and France). However, we've had hundreds of hospitals around the world with thousands of patients. And the drug is cheaply available. What is preventing us to have studies around this in tens of different hospitals? Wouldn't WHO be able to budget this, or actually send people to conduct these studies all across the globe and report back day to day, so within 2 weeks we get a pretty significant set of data?
- dx034 7y ago
  I guess it could be time shortage? You need to bring researchers and doctors together, doctors need to increase documentation on treatment at a time where they are already over capacity, studies need to be approved by regulators and ethic boards etc. The system is not designed to start massive amounts of studies within a week and I'm not sure how much of the red tape can be cut without endangering lives.
- chasil 7y ago
  This drug has actually been mentioned in several past clinical studies on the closely-related SARS. The particular study below has been circulating in several areas online, and has citations to several more: https://cmr.asm.org/content/20/4/660.long https://cmr.asm.org/content/20/4/660.long Despite the role of the pH-sensitive endosomal protease cathepsin L in the entry pathway (151, 300), viral culture does not require pretreatment with trypsin. However, this pH-sensitive cathepsin L may be a target for agents such as chloroquine, which elevates endosomal pH (174, 341).
  - hanniabu 7y ago
    I'm sure I'm not the only one wondering this..... what does this mean in layman's terms?
    - treis 7y ago
      The chemical pathway that allows the virus to enter the cell changes based on the pH of the cell. Chloroquine changes the pH of that pathway and therefore may slow/stop the entry of the virus into the cell.
ekianjo 7y ago
> I don't see how doing poorly performed studys that tell us nothing is of any help. Erm, even poorly designed studies tell you if there's any efficacy to expect or not. And it leads to better studies afterwards. Science is iterative.
- hannob 7y ago
  What do you think this study tells us? The way the authors have analyzed their data it tells us this is a promising drug. Had they done an intention to treat analysis very likely the opposite would've been the result. The only thing that trial tells us is that if you do a bad trial you're as clueless as before.
- _ph_ 7y ago
  I am not a doctor, just a physicist, so I know about experimental data, but of course not about this study in detail. But as several sources dealing with this study confirm, it doesn't really tell us anything. So really at best it can be seen as reason to conduct a proper study, but the data itself does not yield any conclusion.
  - ekianjo 7y ago
    There's a lot in medicine that goes into publication that has results not even borderline as meaningful as this. I would be careful to label this as "it doesn't really tell us anything". Especially since another study in China reached a similar conclusion.
    - davrosthedalek 7y ago
      a) The quality, or lack of quality, of other studies does not affect the quality of the discussed study. b) The availability of another study with similar results, does not affect the quality of this study.
- zeckalpha 7y ago
  Poorly designed studies can lead to expensive and unnecessary followup studies.
jansan 7y ago
I have a question about this article published in The Lancet: https://www.thelancet.com/journals/lancet/article/PIIS2213-2600(20)30076-X/fulltext https://www.thelancet.com/journals/lancet/article/PIIS2213-2... Looking at the drug cocktail that the patient received, this seems to be pretty heavy artillery: - methylprednisolone - moxifloxacin - lopinavir plus ritonavir - interferon - meropenem Holy shit, is this a recommended medication for severe Covid-19 cases?
- Cantbekhan 7y ago
  It seems this man was treated with lopinavir–ritonavir ... Unfortunately according to this recently published study, it seems inefficient against Covid19. https://www.nejm.org/doi/full/10.1056/NEJMoa2001282?query=featured_home https://www.nejm.org/doi/full/10.1056/NEJMoa2001282?query=fe... It also seems some EU countries are now stopping the use of lopinavir due to this study.
  - jansan 7y ago
    I found this "Some centers and even national guidelines, such as those in Italy, have recommended treatment with lopinavir-ritonavir for patients with COVID-19 infection." Not sure what to make of this. Can this to some extent explain the huge differences in death rate between Italy and Germany? Source: https://www.medpagetoday.com/infectiousdisease/covid19/85499 https://www.medpagetoday.com/infectiousdisease/covid19/85499
    - Cantbekhan 7y ago
      As far as the netherlands are concerned, Lopinavir is now removed from their interim guidelines. The first line treatement is now hydroxichloroquine/chloroquine with maybe remdesivir for severe cases. Source (in Dutch): https://swab.nl/nl/covid-19 https://swab.nl/nl/covid-19 But yes in Italy the current guidelines (which are still dated 13 February still mention lopinavir). Source (in Italian): http://www.simit.org/medias/1569-covid19-vademecum-13-03-202.pdf http://www.simit.org/medias/1569-covid19-vademecum-13-03-202... It has also been removed from guidelines from Belgium: source (English) : https://epidemio.wiv-isp.be/ID/Documents/Covid19/COVID-19_InterimGuidelines_Treatment_ENG.pdf https://epidemio.wiv-isp.be/ID/Documents/Covid19/COVID-19_In... I think the odd case is France wich I think is still not having Chloroquine/Hydroxichloroquine in their guidelines as of today. I was not able to find the german guidelines.
ekianjo 7y ago
Criticism on study design during an emergency is fine, but still, we are not talking about some marginal level of efficacy here: https://www.medrxiv.org/content/10.1101/2020.03.16.20037135v1.full.pdf+html https://www.medrxiv.org/content/10.1101/2020.03.16.20037135v... > The proportion of patients that had negative PCR results in nasopharyngeal samples significantly differed between treated patients and controls at days 3-4-5 and 6 post-inclusion (Table 2). At day6 post-inclusion, 70% of hydroxychloroquine-treated patients were virologicaly cured comparing with 12.5% in the control group (p= 0.001). The effect size is huge, even considering the potential biases.
- fabian2k 7y ago
  One of the issues with the study is that they didn't use the clinical outcome as an endpoint, they just measured the virus concentration in the throat (and even that not properly for all cases as far as this HN post says). Huge effect size doesn't matter at all when the effect is not the correct one. There is a significant risk that this surrogate endpoint is not telling the true story as the virus migrates to the lung, measuring in the throat could be very misleading.
  - ekianjo 7y ago
    Is there a reason to believe the viral load in the throat and the lungs would not follow the same trend? And you also forget to mention this (CQ and HCQ concentrate in certain organs): > It has been reported that oral absorption of CQ and HCQ in humans is very efficient. In animals, both drugs share similar tissue distribution patterns, with high concentrations in the liver, spleen, kidney, and lung reaching levels of 200–700 times higher than those in the plasma10. It was reported that safe dosage (6–6.5 mg/kg per day) of HCQ sulfate could generate serum levels of 1.4–1.5 μM in humans11. Therefore, with a safe dosage, HCQ concentration in the above tissues is likely to be achieved to inhibit SARS-CoV-2 infection. https://www.nature.com/articles/s41421-020-0156-0 https://www.nature.com/articles/s41421-020-0156-0
    - fabian2k 7y ago
      Yes, that's one aspect discussed in the podcast with Christian Drosten that is linked in the blog post. This is the relevant part: > We have a lot of experience. We have made the most precise description of an untreated patient cohort among the Munich patients. And at the Munich group, we saw how the virus concentration in both the throat and lungs behaved over time. And we can say that at the beginning of the disease the virus is in the throat and it goes away on its own through the - let's say - the first ten days of the disease. After that, many patients in the throat have little or only irregular evidence of the virus. But that has nothing to do with how the virus behaves in the lungs. The virus is then really replicative in the lungs, especially in severe cases. And we can also say what the patient has in his throat, it has nothing to do with how the clinical development of the disease continues, whether the patient quickly gets well or only goes through a difficult phase. So what is being measured in this entire clinical study has nothing to do with the outcome of the disease, with the symptoms, but is only an initial indicator of how the disease starts. For all patients, the virus concentration drops in the first week, but if you now imagine that the group being treated will be included a little later and the untreated group being included earlier in this study, it is in nature the thing that with this group that was later included - they are already further in eliminating the virus from the throat - that the virus then goes down in the throat, faster. This disappears faster because they have simply been in the course of the disease for a long time. Whether this is due to the fact that they are treated, cannot be said at all from this entire study. Perhaps it would have been so if the groups had been put together as here, but if they hadn't given them chloroquine, but some headache pill, the study would have been the same.
KillerRAK 7y ago
Nothing quite like a site titled "Better Science" with the disclaimer: "While I understand the basics of a clinical trial, I’d like to point out that I am no medical scientists. Most of the issues here were spotted by other people and I have linked to the sources." You cannot make this s@#t up! Put on your critical thinking caps folks -- there's a lot of bad info out there.
- anonymous058 7y ago
  A lot of people, for whatever reason, do not want hydroxychloroquine + azythromycin to work, and would instead prefer we endure 12-18 months of rolling lockdowns.
  - frockington1 7y ago
    I've noticed that too. I think it might be due to all of the doomsday predictions going around on cable news scaring people. If you've just liquidated your 401k into cash at market lows, you're going to want reassurance that it was the correct thing to do
    - throwaway2048 7y ago
      Lets skip the "its the shorters that want you to fail!" conspiracy theories.
- lanewinfield 7y ago
  As soon as I read that line, I closed the window. Not worth it.
  - jstanley 7y ago
    Why? I'd rather get information from a humble expert from a different field than from a braggart who thinks they're an expert.
DocSavage 7y ago
Regarding randomization, the HCQ + Azithromycin study showed good results despite the control group being 14 years younger. Sex was about equal so no male/female imbalance. It’s clear that older patients have worse outcomes, but this study measures viral load which also can change depending on the stage of the disease.
- cycrutchfield 7y ago
  There were 6 patients in that group. No mention of how they were selected. Some patients dropped out of the treatment group because they died or went to the ICU. These could affect the numbers significantly.
thdespou 7y ago
I've read that 2g of this drug can kill you.
- Mountain_Skies 7y ago
  So can 10g of caffeine. As a result, caffeine isn't distributed in ten gram doses.
- frockington1 7y ago
  2 grams of a lot of drugs will kill you. Most doses are in the 50-100 mg range for common drugs
lez 7y ago
Another anti-malaria drug, methylene blue had been proven to work against coronavirus in blood plasma in 2005 [1]. It is used in photodynamic therapy to selectively kill some viruses (see below) / bacteria (e.g. mycoplasma) [2]. When entering the bloodstream, it binds selectively to the nucleus of the viruses it is effective against. It's the same mechanism why it's effective as a dye to stain microbes under microscope. Methylene blue best absorbs light at 660nm wavelength, which at the same time penetrates into human tissues deeply. When light is absorbed, methylene blue disintegrates to harmless molecules while releasing reactive oxygene species, killing the virus. It is a very safe drug, so the same logic that bsaul mentioned could be applied, and therefore would be a responsible move. It is also beneficial to mitochondria and effective against fungus. [1] https://europepmc.org/article/cba/518857 https://europepmc.org/article/cba/518857 [2] https://www.sciencedirect.com/science/article/abs/pii/S1572100005000979 https://www.sciencedirect.com/science/article/abs/pii/S15721...
- hprotagonist 7y ago
  it also literally turns your bodily emissions blue, needs to be administered intravenously, and has some ugly side effects: Common side effects include headache, vomiting, confusion, shortness of breath, and high blood pressure.[1] Other side effects include serotonin syndrome, red blood cell breakdown, and allergic reactions.[1] Use often turns the urine, sweat, and stool blue to green in color.[3]
  - lez 7y ago
    These side effects occur in extremely high doses, much much higher than the effective dosage. It doesn't need to be administered intravenously (only for methemoglobenia) - although more effective that way. serotonin syndrome, rbc breakdown and allergic reactions occur when you drink a glass of what few drops are enough. As said, it is extremely safe drug in low dosages (4-16 drops of 0.1% solution). Edit: Also see the Kevin Rose Show episode https://podcast.kevinrose.com/dr-peter-attia-longevity-compounds-fasting-supplements-and-more https://podcast.kevinrose.com/dr-peter-attia-longevity-compo... starting @ 1:16:20
- tootie 7y ago
biolurker1 7y ago
I like facts. Article says only French study exists but at least a couple of other studies exist from China. I wish when someone makes a very important argument to check all internet sources.
stevespang 7y ago
Here we go, another naysayer. Unfortunately, all those waiting patiently for "confirmed results of double blind trials" will make up a significant percentage of those visiting the pearly gates by the time those trials are ever completed. Look, the risk is fairly low for chloroquine, mild side effects in a very well done Danish study were only ~15%, serious side effects were ~1.5%. Reported Side Effects to Chloroquine, Chloroquine plus ... academic.oup.com › jtm › article-pdf › jtm7-0079 Now, what's the risk of serious side effects/death from coronavirus for those over 70 years old ? Like >10%. And a recent report out of Hong Kong is stating that lung scarring from coronavirus is being found in all ages (radiological imaging), like 20 to 30% loss of lung function, shortness of breath reported by recovered patients just from fast walking - - - is that going to be permanent in all ages ? Are you willing to take that risk ? A glaring fact is that chloroquine / hydroxychloroquine have been on the WHO's list of essential medicines for decades . . . . why so, if they were too toxic to recommend ? Just like the rush on buying ammo, would you prefer to have "the likely treatment" before the problems comes to you - - or, would you prefer to fail to find it after all the shops and stores are completely sold out and the unemployed "zombies" are all over your property and smashing down your door while your family is cowering under the table screaming and crying for help ? I already got my supply of it, best of luck for all the naysayers. https://www.foxnews.com/health/florida-man-with-coronavirus-claims-malaria-drug-saved-life https://www.foxnews.com/health/florida-man-with-coronavirus-... https://video.foxnews.com/v/6143849011001 https://video.foxnews.com/v/6143849011001 BTW, what is your Gov't offering you right now in the way of proven drugs ? Nothing. All the while the rich in NY are reported in the news media as cashing in on favors to secure reservations for hospital beds in case they need them - - and buying ventilators . . . under the counter.
axguscbklp 7y ago
The numerous* stories that I have read recently about medical professionals writing themselves prescriptions for hydroxychloroquine so that they can have it available for themselves and their families suggests to me that the French trial is not the only reason to be hopeful about hydroxychloroquine's efficacy against COVID-19. Sure, medical professionals are not necessarily any kind of super-rational savants, but I think it's unlikely that all of the medical professionals who are trying to hoard hydroxychloroquine are being irrational hysterics. They might be engaging in ethically questionable acts by hoarding hydroxychloroquine, but that doesn't mean that they don't know what they're doing from a self-preservation standpoint. That said, it's not that I think they are necessarily trying to hoard hydroxychloroquine because they are convinced that it works - it's probably more that they want it on hand in case it turns out that it works. However, some of them may also have directly seen it help people, or may have heard or read about it helping. Given that hydroxychloroquine has already been used for, as I understand it, weeks in treating people ill with COVID-19, I am actually surprised that there is not more anecdotal evidence about its efficacy. But I probably have just not been reading in the right places. *Edit: I probably shouldn't have said "numerous stories", since "numerous" implies more than the number that I actually have seen.
- brm 7y ago
  If you're going to make these statements you should also share what you've been reading...
  - axguscbklp 7y ago
    Sure. Here are a couple of places with sources. https://old.reddit.com/r/medicine/comments/flor5z/please_stop_prescribing_hydroxychloroquine_for/ https://old.reddit.com/r/medicine/comments/flor5z/please_sto... https://www.mahoningmatters.com/regional-news/ohio-doctors-accused-of-hoarding-potential-coronavirus-treatments-2188449 https://www.mahoningmatters.com/regional-news/ohio-doctors-a...
  - DataWorker 7y ago
    https://www.washingtonpost.com/business/2020/03/20/hospitals-doctors-are-wiping-out-supplies-an-unproven-coronavirus-treatment/ https://www.washingtonpost.com/business/2020/03/20/hospitals...
jeffdavis 7y ago
It seems like the answer is "more science". Given how the virus is moving now, couldn't we have a pretty nice study completed in a few weeks?
roenxi 7y ago
Why are we so excited about the French trial? What about the Chinese treatment guidelines [0]? The Chinese recommend chloroquine phosphate. They've had more experience than anyone else in this area and have had time to conduct actual trials. The disease has a ~2-4 week course so it should take about that long to gather compelling evidence; and they've been dealing with it since January. The French are clever people, but we really should be looking to Asia for this information. People should be finding and quoting Chinese studies. [0] http://kjfy.meetingchina.org/msite/news/show/cn/3337.html http://kjfy.meetingchina.org/msite/news/show/cn/3337.html 10(b)(4)
- klmadfejno 7y ago
  The featured article claims that references to the supposed Chinese studies don't turn up anything. And that seems to be true. Here is the Chinese cited material from the French article: https://www.jstage.jst.go.jp/article/bst/14/1/14_2020.01047/_article https://www.jstage.jst.go.jp/article/bst/14/1/14_2020.01047/... It claims many clinical trials have been done in China that show chloroquine works. However... there's nothing to actually read with any data.
- deleted 7y ago
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Bhilai 7y ago
Related: Novartis commits to donate up to 130 million doses of hydroxychloroquine https://www.novartis.com/news/media-releases/novartis-commits-donate-130-million-doses-hydroxychloroquine-support-global-covid-19-pandemic-response https://www.novartis.com/news/media-releases/novartis-commit...
klmadfejno 7y ago
A lot of people are eager to say chloroquine is the answer and say, "forget the small details, look at that p-value!". But this article raises a bunch of important points. The important ones IMO are: 1) 6 / 26 of the individuals in the experimental group got removed from the stats because their condition got worse and the treatment ceased. One of them died. 2) The metric used to test the efficacy is viral load. You can get a negative on this and still have the disease. This is going to be a function of how long you've had the disease, which isn't controlled in the study. If you have a gripe with the author because they're not a medical scientist, read the peer review comments here: https://pubpeer.com/publications/B4044A446F35DF81789F6F20F8E0EE#2 https://pubpeer.com/publications/B4044A446F35DF81789F6F20F8E... They are easy to understand as a layman I feel. Other noteworthy takeaways: 1) The combination of HCQ and AZ was hyped as superior because all 6 patients did better. But looking at the data there is no significant difference in viral load outcomes between both drugs and just HCQ. 2) Many of the author's claims of statistical significance disappear if you use more conservative estimates for when people were supposed to be PCR positive except for Day 6 (now 0.01 instead of 0.001). 3) The paper turnaround was incredibly fast, with less than 24 hours for peer review. One of the authors of the paper is an editor of the journal in which it was published. Could be indicative of poor study controls. I hope this turns out to be useful. I would not be surprised if it did not. Regardless, the best case takeaway of THIS information does not inform us about how the drug performs in the most critical area (severe ICU patients). If you're a non-bio programmer please try to recognize that saying the current paper is good enough to justify mass distribution of chloroquine tablets to everyone is about on par with the cliche clueless product manager making bold decisions about how to move forward with your codebase despite having no clue how it works themselves.
gyrgtyn 7y ago
why is every study i've ever seen posted somewhere deeply flawed -in some way that is obvious to even non-experts?
pbreit 7y ago
Sure is a lot of energy going into trying to debunk this report and chloroquine in general. Is it because Trump mentioned it?
- m0zg 7y ago
  You're just witnessing the old joke IRL: If Trump could walk on water, the Left would complain that he can't swim. I'm not saying this works, but it does seem to me that for severely ill patients there's no harm in doing a large-ish field trial. Prophylactic use should receive more scrutiny.
  - rplst8 7y ago
    Right. Like why not give it to those willing to try who can't get a vent in Italy.
    - m0zg 7y ago
      They do in fact "give it to those willing to try" in Italy, France, and China at a minimum. Probably elsewhere as well. Here in the US we're instead engaging in purely partisan bickering as to whether or not it should be available (which is not the same thing as pervasive use).
  - TomMckenny 7y ago
    >You're just witnessing the old joke IRL: If Trump could walk on water, the Left would complain that he can't swim. The skepticism is due to false claims like "anybody that wants can get a test" [1] But as you say, maybe they shouldn't blame Trump since he says it's not his responsibility [2] Anyway, why do any treatment if the virus is a hoax[3], hype[4] and fake news[5] Or at worst, it is only one person coming from China and is totally under control [6] Certainly the president is not concerned at all about the White-house [7] And all this must be true because has has known it was a pandemic all along [8] [1] https://www.whitehouse.gov/briefings-statements/remarks-president-trump-tour-centers-disease-control-prevention-atlanta-ga/ https://www.whitehouse.gov/briefings-statements/remarks-pres... [2] https://youtu.be/NezEbDx4B9A?t=102 https://youtu.be/NezEbDx4B9A?t=102 [3] https://youtu.be/NezEbDx4B9A?t=57 https://youtu.be/NezEbDx4B9A?t=57 [4] https://twitter.com/realDonaldTrump/status/1236975196642390022 https://twitter.com/realDonaldTrump/status/12369751966423900... [5] https://twitter.com/realDonaldTrump/status/1237004509156642816 https://twitter.com/realDonaldTrump/status/12370045091566428... [6] https://www.cnbc.com/2020/01/22/trump-on-coronavirus-from-china-we-have-it-totally-under-control.html https://www.cnbc.com/2020/01/22/trump-on-coronavirus-from-ch... [7] https://youtu.be/NezEbDx4B9A?t=78 https://youtu.be/NezEbDx4B9A?t=78 [8] https://youtu.be/NezEbDx4B9A?t=109 https://youtu.be/NezEbDx4B9A?t=109
MisterBastahrd 7y ago
https://nypost.com/2020/03/19/sales-of-fish-tank-additive-skyrocket-after-studies-say-it-could-treat-coronavirus/ https://nypost.com/2020/03/19/sales-of-fish-tank-additive-sk... This is the kind of idiocy that pie-in-the-sky theatrical crap like this causes. People are going to end up seriously harming if not killing themselves by taking this stuff.
Avshalom 7y ago
https://thehill.com/policy/healthcare/489097-man-dies-after-taking-malaria-medication-in-effort-to-prevent-coronavirus https://thehill.com/policy/healthcare/489097-man-dies-after-... well that took what, two days?
max_ 7y ago
Chloroquine was banned years ago in my country due to its toxic effects (was making kids deaf amongst other things). Are its downsides worth the upsides when used as a COVID-19 treatment?
- Zak 7y ago
  The course of treatment is short, while some applications of chloroquine are long-term. The risk is likely considerably reduced.

191 points by hannob 7y ago

Also on HN: https://www.sciencemag.org/news/2020/03/who-launches-global-megatrial-four-most-promising-coronavirus-treatments https://www.sciencemag.org/news/2020/03/who-launches-global-... Testing will be randomized apparently.

ncmncm 7y ago
Maybe change the link in the header?

deleted 7y ago

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bsaul 7y ago

I see many problems with all the caution around that study: 1/ chloroquine is a very well known cheap drug. There is no new risk associated to using it that doctors arent already aware of. 2/ we do have a lot of statistics now on the outcome of patient not treated with that drug. There's no need for establishing a benchmark. Just proper categorization of existing patient should be enough to compare. 3/ people are oversaturating ICU right now. And as such, it is an emergency situation. We should take the reverse reasoning we usually take : if there's no suscipicion this drug could cause new problems, we should have people massively use it whenever possible and look at the result after 6 days (since that's the time the original study says it takes for the first results to show).

ncmncm 7y ago
In particular, if it turns out to reduce infection rate, taking it prophylactically will save the lives of everyone who would otherwise die for lack of a ventilator, or who would die even with one. If it does not turn out to reduce infection rate, no harm done. If it turns out to shorten the illness, everyone sick, and also everyone taking it prophylactically who is actually infected but asymptomatic, will reduce their contagion rate by joining the ranks of the non-contagious sooner, reducing everyone's risk. If it does not turn out to shorten the illness, no harm done. Chloroquine is well-known. If it caused an unacceptable rate of liver failure we would already know. I see suggestions that it takes a very high doses to work. But that might be so only for the already severe infections they are using it on. It should be easy enough to discover whether low doses work prophylactically, and safe enough to try them while waiting on results.
- joe_fishfish 7y ago
  What if it turns out to shorten the illness in 80% of cases but cause liver failure in the other 20%?
  - learc83 7y ago
    It's a well known drug. We already know the side effects.
    - kl4m 7y ago
      Not on people with COVID-19.
  - tyingq 7y ago
    Hydroxychloroquine is significantly less hepatoxic than chloroquine.
henriquez 7y ago
Exactly. Since the risks and side-effects are well-established, it’s more ethical at this point to experiment on humans with an “off label” usage. Doctors do that all the time with other meds.
- _ph_ 7y ago
  Yes, doctors should experiment with the drug and I am certain, a lot of those, who have the necessary conditions to perform a proper experiment, will do. What should not happen now is, that the general public starts taking the drug as a precaution, just because it might work. The known side-effects are too severe (e.g. blindness) and also, there are already shortages of the drug for those who already require it as part of their medical treatment (e.g. immune-supressed).
  - ekianjo 7y ago
    > Blindness This side effect occurs if you take chloroquine for extended periods of time. Look at the data. https://eyewiki.aao.org/Hydroxychloroquine_toxicity https://eyewiki.aao.org/Hydroxychloroquine_toxicity "Risk for toxicity is less with <5.0 mg/kg real weight/day for hydroxychloroquine and <2.3 mg/kg real weight/day for chloroquine[2]. Patients are at low risk during the first 5 years of treatment." And management is as simple as stopping the drug if it starts affecting your vision: "At the first signs of retinal toxicity, hydroxychloroquine should be stopped to prevent further retinal damage and visual loss[2]. "
    - kevingadd 7y ago
      I'd note that the phrase "further retinal damage and visual loss" implies that retinal damage and visual loss has already occurred... how much of that you are willing to tolerate is up to you, I suppose: I'd prefer 0 unless necessary. If the retinal damage is saving me from a death at the hands of COVID-19 maybe it's worth it, but if it's not...
      - ekianjo 7y ago
raverbashing 7y ago
I have similar thoughts This is not some crazy experimental new drug that was unknown until past week. It's an experimental treatment, it's not an experimental drug, with unknown side effects. For a condition where time is critical. Of course, we should also be quick to discard unpromising drugs, and not only focus on one promising drug. WHO is starting a megratrial of several drugs now https://www.sciencemag.org/news/2020/03/who-launches-global-megatrial-four-most-promising-coronavirus-treatments https://www.sciencemag.org/news/2020/03/who-launches-global-... (including CQ/HCQ)
jonathanstrange 7y ago
This is irresponsible. This drug has severe side effects, it makes absolutely no sense to prescribe it for a completely different disease without first confirming in clinical trials that it has positive effects. > if there's no suscipicion this drug could cause new problems, we should have people massively use it That's not how evidence-based medicine works. The drug is known to cause new problems because of the side effects. Clinical trials are needed to determine whether these are outweighed in patients by positive health effects. You do not prescribe medicine on the basis of hunches.
- _red 7y ago
  You are currently running another experiment called: Crash the global economy. That's also irresponsible. Should 10-yr olds be forced to give their life to save 85 yr olds?
  - JoeAltmaier 7y ago
    Maybe a bit of strawman there. With more information (hopefully coming) we should be able to make more nuanced decisions.
- ekianjo 7y ago
  > This is irresponsible. This drug has severe side effects What are you talking about? The severe side effects are known and are usually associated with chronic usage of that drug. Chloroquine is taken for prophylaxis against malaria (daily) in many places in the southern hemisphere. Usual regimen is at least for 8 continuous weeks! EDIT: Toxicity here: as you can see it's very well tolerated. https://eyewiki.aao.org/Hydroxychloroquine_toxicity https://eyewiki.aao.org/Hydroxychloroquine_toxicity
  - jonathanstrange 7y ago
    The suggestion on the table is to give this drug to extremely ill patients who suffer from a new viral disease on the basis of anecdotal evidence and without clinical trials. The suggestion was to massively prescribe it. What health authorities want to do is to allow physicians to use the drug if the patient agrees, but only in a controlled setting in which data is collected and there is a control group. So at least afterwards we could draw conclusions about whether it killed more people or helped saving people. Does that not make sense to you?
hannob 7y ago
Opinions like this seem to be popular these days, but they're dangerous. Because this is an emergency we want reliable information. Think about it like this: If these researchers had done a proper trial - and there's absolutely no reason to think that they couldn't have done that in the same amount of time with the same amount of effort - then we'd actually know something useful now. With that trial - we don't.
- throwaway_pdp09 7y ago
  Agreed, this kind of thinking comes from fear and desperation (and another kind is denial of reality - this can't be happening so it isn't. My neighbours still don't realise it's actually happening). If we want to deal with covid we should have started years ago. As ever, we didn't.
- hanniabu 7y ago
  > Because this is an emergency we want reliable information. So much for that given the president was recommending chloroquine to be used off the cuff.
- pbreit 7y ago
  "no reason to think that they couldn't have done that in the same amount of time with the same amount of effort" There is EVERY reason to think they were not in a position to a "proper" test. They are in the middle of an epidemic!
- ping_pong 7y ago
  They are in a war zone in Italy and presumably in the US very soon. If hydroxychloroquine is safe (except for some people with a known predisposed genetic condition), then we should be giving it widely and early. We can worry about the science and studies later on, but right now we need to save lives and decrease ICU overload.
- tim333 7y ago
  This was done in about a week. Where's an example of a clinical trial to your liking done that quickly?
httpsterio 7y ago
Being sick with a disease like Covid-19 could absolutely alter how a medication works on a person. The drug might be safe to a person with a certain profile and it has been tested against those, but each underlying issue is a new profile which it should be tested against as separately as possible.
- guiriduro 7y ago
  I think this is the fairest counter-argument I've heard so far about safety of HCQ in Covid-19. I still think the background of "you're in a house burning down, some tests tentatively indicate this may be effective..." weigh more against the risk of side-effects or worse progression due to CQ/HCQ. We ought to be able to devise some experiments to add certainty, using mainly retrospective data now available. Most SLE/Lupus patients take HCQ, and reportedly none in the cohort of the doctor I know have sufficiently severe symptoms to qualify for pCR testing to even establish if they have Covid19. This is Spain with (currently) 708 cases per MM. Of course, caveats like absence of evidence is not (necessarily sufficient) evidence of absence. It may be that SLE or other immuno-modulation treatments have some effect - someone should do analysis with matched non-SLE HCQ and non-HCQ prophylaxis cohorts. But back to my main point with the house burning metaphor for exponential infection - the risk landscape demands we take more risk, give HCQ widely instead of waiting for the conclusion of prospective studies. We can withdraw it if it is shown to be no better than placebo or worsens outcomes when enough data is available to conclude.
- dcolkitt 7y ago
  Based on that reasoning, we shouldn't give any pharmaceuticals to coronavirus patients. Even simple fever relievers, like acetaminophen, or oral rehydration fluids should be prohibited because we just don't have enough data to know how they'll interact with COVID-19 specifically.
lultimouomo 7y ago
> 3/ people are oversaturating ICU right now. And as such, it is an emergency situation. From what I can gather chloroquine is already used as a first line treatment in Italian hospitals (at least it is indicated as such by the COVID treatment guidelines published by the society of Italian infectious disease specialists [0], and has been for quite some time - this document is from 10 days ago, but an earlier revision was not different regarding chloroquine). If this is the case, it's pretty clear that this is no miracle cure - it has at best a marginal effect. [0] http://www.simit.org/medias/1569-covid19-vademecum-13-03-202.pdf http://www.simit.org/medias/1569-covid19-vademecum-13-03-202...
- raverbashing 7y ago
  Thanks for this reference, it seems they are proposing 2 potential treatments (p. 13) for the more severe patients > Il trattamento deve essere accompagnato da trattamento antivirale (lopinavir/ritonavir o remdesivir + clorochina/idrossiclorochina) e/o steorideo (desametasone) This is from the 13th of March so I guess there will be still some days until we see results of this (either positive or negative)
  - dcolkitt 7y ago
    For the record since that decision day, the growth rate in the number of deaths in Italy has fallen in half[1]. In the 9 days from March 13 to March 22 the daily number of deaths grew 160% from 250 to 651. Prior to that, the same level of growth occurred in 4 days between March 9 (96 deaths) to March 13. That seems like pretty strong evidence that the new treatment protocol is drastically decelerating the pandemic in Italy. [1]https://www.worldometers.info/coronavirus/country/italy/ https://www.worldometers.info/coronavirus/country/italy/
    - lultimouomo 7y ago
      This does not make much sense to me. If it was effective, it should decrease the lethality rate, not the growth in the number of deaths which is much more affected by the actual number of cases. In the page you link you can see that lethality rate has not fallen. Also, as I wrote I'm pretty sure that I saw an earlier version of that document, dating IIRC to the beginning of the month, that prescribed more or less the same combination of chloroquine and antivirals as a first line treatment.
jpz 7y ago
It isn't vitamin C. It has a lot of side effects, including serious psychiatric ones in limited cases. If you give it to 100 people you're going to get new health issues that you didn't have before in that population.
- jansan 7y ago
  Interestingly there is a trial to use a high dose of vitamin C to treat COVID-19 ARDS: https://youtu.be/bt-BzEve46Y?t=2107 https://youtu.be/bt-BzEve46Y?t=2107
kingkawn 7y ago
You cannot pour a drug into the populace that will cause side effects on a mass scale that might also overwhelm the healthcare system. It is nice to imagine we have the medicine already, that we can simply wave our hands distribute the pills and everything can go on as it was before this. But we do not and can not go back.
wpietri 7y ago
This is absurd: > There is no new risk associated to using it that doctors arent already aware of. You're imagining that their might be an unknown benefit using it with a novel disease, but you're confident that there won't be unknown risks? Drugs just have effects. Risk/benefit is a human construction we apply over the top. There's no reason to expect only good surprises here.
- tim333 7y ago
  Though why should it have weird side effects when used for COVID that it didn't when used for malaria?
  - wpietri 7y ago
    As I said, drugs just have effects. Humans then look at the results, decide which are good and bad, and then label the bad ones "side effect". So I think the real question is: why do you think 100% of the novel effects will be later put in the "good" bucket?
m0zg 7y ago
Yeah, it's important to have it available if it's needed and it's important to conduct at least some sort of trial. Because the drug, combined with azithromycin is so fast acting, we should see the first results in a few days. Worst thing that can happen is it doesn't work. Best thing that can happen is we can save 1.8 trillion dollars and restart the economy. Under these circumstances one would be an idiot not to give it a try. Coughing your lungs out but feel like CNN is not lying to you? Easy! Refuse the drug. Nobody can force you to take it.
- DanBC 7y ago
  > Worst thing that can happen is it doesn't work. Worst thing that can happen with a chloroquine and azithromycin combination is that it causes heart arrhythmia and sudden death in a patient that would not have otherwise died. Studies of patients taking this combination of meds include daily EKGs, which is something the general population at home isn't going to have access to. https://twitter.com/search?q=azithromycin%20qt&src=typed_query https://twitter.com/search?q=azithromycin%20qt&src=typed_que...
  - m0zg 7y ago
    That's why they are starting with a trial, and not a full scale roll out. Other countries are using this combination of drug, and it's not because they're huge fans of Trump, I can assure you. We also have literally millions of devices out there capable of detecting arrhythmia - they're called Apple Watch.
    - snegu 7y ago
      Apple Watch can't detect long QT, which is one of the risk factors here.
      - m0zg 7y ago
        That's like saying construction N95 masks can't be used in the medical setting just because they lack appropriate certification. That old shibboleth has been defenestrated weeks ago. I bet it can, if FDA is beat over the head with a shovel, which it will be if the need arises. It's a real ECG verifiably capable of detecting irregular hearth rhythm, and it costs a tiny fraction of what a big-ass ECG machine would, and therefore can be deployed at a much larger scale. Just because it could only get approval to detect atrial fibrillation duing "peacetime" doesn't mean it can't be pressed into service for other things.
gus_massa 7y ago
> There's no need for establishing a benchmark. Just proper categorization of existing patient should be enough to compare. This is very difficult to do. In this study all the patients in the treatment group are from a hospital and most of the patients in the other hospital are from other hospital. Do the population of both hospitals have the same median income? Usually a low income cause a bad diet that may cause bad health that has a worse prognosis. Are the patients in the other countries classified by income? Does the difference in income cause more/less consumption of milk? Bottled milk has an additional amount of vitamin D, and some unconfirmed reports say that the lack of vitamin D is bad for covid19. Does this difference depend on the country? For historical/genetic reason, French drink more milk that Chinese. What about wine, is the consumption of wine important? What is the effect of temperature and humidity in the no-hydroxychloroquine group? The average climate conditions change from country to country and from place to place and from month to month. To be included in the testing group the patient must give consent. Probably they have not to be too wasted to be able to read it. Probably not been to wasted is a good sign. There are a lot of factors, and not all of them are known, not all of them are easy to measure, not all of them are measured. So you need a control group.
rsynnott 7y ago
> chloroquine is a very well known cheap drug. There is no new risk associated to using it that doctors arent already aware of. I mean, you could say the same of practically any older drug. It's a fairly well-understood, cheap, somewhat dangerous drug. > we do have a lot of statistics now on the outcome of patient not treated with that drug. Sure. We also have a lot of statistics on the outcome of patients not treated with thalidomide, and morphine, and basically any other cheap somewhat dangerous drug you care to mention. > if there's no suscipicion this drug could cause new problems While I don't think there are, there's the certainty that it will cause the usual old problems that this drug causes. Which you probably don't want when you also have covid-19. We'd be better off waiting on a proper trial.
- TheHypnotist 7y ago
  We know the side effects for a healthy individual or those with malaria, but how do we know for certain this won't cause new problems in those with COVID-19?
mrfusion 7y ago
You’re absolutely right. We need to act fast.
jcrubino 7y ago
2) It complicates the treatment of the patients who will experience the worst cases of COVID-19 causing panic... people above 65 with diabetes and heart conditions. 3) Again this drug has well known precautions that reads like the all the people who will experience the worst of COVID-19 Having Grandpa John walk in for COVID-19 and roll out for death by QT elongation is not something the public will have to litigate.
- dcolkitt 7y ago
  > Again this drug has well known precautions that reads like the all the people who will experience the worst of COVID-19 Except those precautions are at least two orders of magnitude less than the case fatality rate for coronavirus infection. Equivalently, there are scenarios where a seatbelt can decapitate you or trap you in a drowning car. But you'd still be a fool to drive without one, because buckling is a thousand times more likely to save you than kill you.
  - jcrubino 7y ago
    You missed the point. The most serious cases of COVID-19 affect all the people who have the underlying conditions that have precautions listed using H-Chloroquine. That makes the normal ICU case of COVID-19 more difficult (time consuming) to manage because now you have to spend time managing / monitoring: The condition, COVID-19, the side effects of H-Chloroquine on vital body systems already impaired, already being attacked by COVID. Throw the magnitude two out the window like a lucky car crash victim while these patients suffer the crash in the hospital. Not even Bernie was going to pay for the specialty concierge care needed to manage such a patient and yet you some how assume that is how it works.
epistasis 7y ago
> we do have a lot of statistics now on the outcome of patient not treated with that drug. There's no need for establishing a benchmark. Just proper categorization of existing patient should be enough to compare. This is very wrong; we have good aggregate statistics across lots of different hospitals, but for a study with a small number of sites where the patients are treated with the drug, there's enough inter-site variability that may obscure any effect, or create a false effect. This is doubly true as health care varies as sites get overwhelmed, and healthcare workers get increasingly strained from long shifts. There will be far more variability as time goes on. And for how small we expect the effect to be, based on the data in the paper, we really should include controls. All that said, I think that the publication of this flawed study is very good, and why pop-science takes that excoriate science as "most research finding are false" really communicate the wrong way to think about science, and limit its applicability. Flawed datasets like this still give us clues, and publishing flawed data is still useful to others to accelerate the pace of science. Which is why we need to take the attitude that publications are point in time guesses at what's going on, and only rarely does one come out that can be considered on its own as definitive, and that it's good to have mostly "here's some data and analysis but we don't have a complete theory yet"-type-papers. Without those intermediate publications, science would grind to a halt.
- dcolkitt 7y ago
  > but for a study with a small number of sites where the patients are treated with the drug, there's enough inter-site variability that may obscure any effect, or create a false effect. The simple solution is to spread it over enough sites so that the law of large numbers quantifies that variability into the dataset. For example if we run trials over 10 hospitals in 20 different states, 200 sites in the dataset would almost certainly capture inter-site variance.
  - akiselev 7y ago
    That only normalizes natural variances in your patients, not artificial biases introduced by the healthcare system. Pump and other hardware measuring out dosages might come from different manufacturers or be calibrated and serviced by different technicians. Maybe the study includes one too many hospitals in a region dominated by one manufacturer whose hardware tends to error more in one direction than other manufacturers. The generics used by pharmacies and hospitals might be slightly different because of local relationships. Exercise, ability to have visitation in quarantine, and other amenities in hospitals will have differing impacts on confounding factors like exercise and morale. And on and on. There are a bunch of "contract research organizations" all over the world, quite a few of them making billions of dollars a year, who specialize only in running clinical trials because these things are so complicated. The documentation for clinical trials are often thousands of pages long describing tiny details like device calibration across hospitals trying to eliminate as many risks as possible. These organizations tend to have long standing relationships with hospitals and host many different trials in each one with a bunch more subcontractors who do patient selection.
herf 7y ago
Check PDR before you say things like this: https://www.pdr.net/drug-summary/Plaquenil-hydroxychloroquine-sulfate-1911.7193 https://www.pdr.net/drug-summary/Plaquenil-hydroxychloroquin... Has side effects in patients with G6PD deficiency (10-15% in some populations) Cardiotoxicity, retinopathy, and these are especially likely in older patients. https://www.bloomberg.com/news/articles/2020-03-20/virus-drug-touted-by-trump-musk-can-kill-with-just-two-grams https://www.bloomberg.com/news/articles/2020-03-20/virus-dru... Disclaimer: am not a MD or public health person, but I talk to both.
aaavl2821 7y ago
Many doctors are already actively prescrbign this. I heard that it is basically de facto standard of care in France. Doctors recognize that when eveidence based medicine doesn't provide an adequate treatment, they need to improvise. Off-label prescribing is very common The point of these studies is to help the evidence catch up to improvised clinical practice. If the studies are poorly designed, that goal is not achieved
eagsalazar2 7y ago
I imagine some country/region out there will adopt this approach so we'll all get to find out in a few weeks (possibly at their expense).
- jansan 7y ago
  It is being used in several countries already (US and Europe, not sure about Asia). If you are interested in details, here is a video of a conference call at UCSF: https://youtu.be/bt-BzEve46Y?t=3194 https://youtu.be/bt-BzEve46Y?t=3194
IAmEveryone 7y ago
Your second and third point are completely independent of the substance at issue. So by that logic, we should test everything that is “safe”. Prayer? Meditation? Garlic? Red wine? Cannabis?
- perl4ever 7y ago
  https://en.wikipedia.org/wiki/Generally_recognized_as_safe https://en.wikipedia.org/wiki/Generally_recognized_as_safe ...I mean it is a big loophole. Something I've wondered about for years is V-8 juice. Seems healthy, but what about the psoralens in celery? I'm not saying that everything does need to be tested, but if you don't, you don't really know and no mental gymnastics can change that.
naasking 7y ago
> There is no new risk associated to using it that doctors arent already aware of. You can't possibly know whether this drug would have adverse interactions with a new illness.

Cantbekhan 7y ago

If you are curious, this is the actual Chinese trial registration (edit: not results) about hydroxichloroquine (among the many citations in the pdf) http://www.chictr.org.cn/showprojen.aspx?proj=48880 http://www.chictr.org.cn/showprojen.aspx?proj=48880

hannob 7y ago
Just to make this clear: This is a trial registration, not a result.
chvid 7y ago
Is this an ongoing trial? When are the results due? 3x100 subjects (is that correctly read?) seems quite powerful.
- Cantbekhan 7y ago
  Yes it seems they have 100 on one dosage, 100 one a different dosage and 100 in a placebo group. According to the register, the study execution time should be "2020-01-31 To 2020-02-29" But nobody seems to have any insight on the final results. But I would recommend this article with comments of the study leader (Dr Zhang Zhan). The article also explains how they initially discovered the efficiency of the drug by just noticing there were no lupus patients (who were under chronic treatment of hydroxichloroquine) infected with covid19. https://www.jqknews.com/news/388543-The_novel_coronavirus_pneumonia_has_short_term_curative_effect_on_the_treatment_of_new_crown_pneumonia.html https://www.jqknews.com/news/388543-The_novel_coronavirus_pn...
  - hanniabu 7y ago
    > But nobody seems to have any insight on the final results. I assume that means it's either too small of a sample size or it doesn't make enough of an affect?
    - zeckalpha 7y ago
      A study designed like this shouldn’t have data analysis before it is all collected.

sanxiyn 7y ago

Favipiravir trial result is out and the result looks good: https://www.medrxiv.org/content/10.1101/2020.03.17.20037432v1 https://www.medrxiv.org/content/10.1101/2020.03.17.20037432v...

ncmncm 7y ago
There has also been success with Avastin (bevacizumab), although the WHO does not seem to be pursuing it. https://clinicaltrials.gov/ct2/show/NCT04275414 https://clinicaltrials.gov/ct2/show/NCT04275414
- adrianN 7y ago
  Since it ends in mab I assume it's a monoclonal antibody. Those are expensive as fuck because they're so difficult to make. I wonder whether we could scale production up to meet pandemic demand.
  - hprotagonist 7y ago
    mabs are not a straight small molecule synth. Scale as much as you want, growing them takes a while even in parallel. (this is more or less also why vaccine timelines are so long; chicken eggs take a bit of time to get going, and that's the best breeding ground we have!)
deskamess 7y ago
The world needs something that is accessible. "As of 23 March 2020, it seems that Japan and China have issued an export ban on the substance. Japan and China are the only countries in which favirapir is produced and approved as a medical compound." [1] [1] https://en.wikipedia.org/wiki/Favipiravir https://en.wikipedia.org/wiki/Favipiravir
- dx034 7y ago
  And I guess setting up factories to produce millions of doses of new meds can take a while. At the same time, each new manufacturer has to negotiate terms with the patent holder. Using an existing cheap generic drug means that production facilities are already up and running and that any company could start if they have the means to produce it. Apparently a 1-month dose costs £5 in the UK, so there doesn't seem to be a large hurdle to produce it.

emilsedgh 7y ago

I have 0 clues about clinical trials and the procedures. My questions is: Why are so few studies done on this? I think so far we have 2 studies. (from China and France). However, we've had hundreds of hospitals around the world with thousands of patients. And the drug is cheaply available. What is preventing us to have studies around this in tens of different hospitals? Wouldn't WHO be able to budget this, or actually send people to conduct these studies all across the globe and report back day to day, so within 2 weeks we get a pretty significant set of data?

dx034 7y ago
I guess it could be time shortage? You need to bring researchers and doctors together, doctors need to increase documentation on treatment at a time where they are already over capacity, studies need to be approved by regulators and ethic boards etc. The system is not designed to start massive amounts of studies within a week and I'm not sure how much of the red tape can be cut without endangering lives.
chasil 7y ago
This drug has actually been mentioned in several past clinical studies on the closely-related SARS. The particular study below has been circulating in several areas online, and has citations to several more: https://cmr.asm.org/content/20/4/660.long https://cmr.asm.org/content/20/4/660.long Despite the role of the pH-sensitive endosomal protease cathepsin L in the entry pathway (151, 300), viral culture does not require pretreatment with trypsin. However, this pH-sensitive cathepsin L may be a target for agents such as chloroquine, which elevates endosomal pH (174, 341).
- hanniabu 7y ago
  I'm sure I'm not the only one wondering this..... what does this mean in layman's terms?
  - treis 7y ago
    The chemical pathway that allows the virus to enter the cell changes based on the pH of the cell. Chloroquine changes the pH of that pathway and therefore may slow/stop the entry of the virus into the cell.

ekianjo 7y ago

> I don't see how doing poorly performed studys that tell us nothing is of any help. Erm, even poorly designed studies tell you if there's any efficacy to expect or not. And it leads to better studies afterwards. Science is iterative.

hannob 7y ago
What do you think this study tells us? The way the authors have analyzed their data it tells us this is a promising drug. Had they done an intention to treat analysis very likely the opposite would've been the result. The only thing that trial tells us is that if you do a bad trial you're as clueless as before.
_ph_ 7y ago
I am not a doctor, just a physicist, so I know about experimental data, but of course not about this study in detail. But as several sources dealing with this study confirm, it doesn't really tell us anything. So really at best it can be seen as reason to conduct a proper study, but the data itself does not yield any conclusion.
- ekianjo 7y ago
  There's a lot in medicine that goes into publication that has results not even borderline as meaningful as this. I would be careful to label this as "it doesn't really tell us anything". Especially since another study in China reached a similar conclusion.
  - davrosthedalek 7y ago
    a) The quality, or lack of quality, of other studies does not affect the quality of the discussed study. b) The availability of another study with similar results, does not affect the quality of this study.
zeckalpha 7y ago
Poorly designed studies can lead to expensive and unnecessary followup studies.

jansan 7y ago

I have a question about this article published in The Lancet: https://www.thelancet.com/journals/lancet/article/PIIS2213-2600(20)30076-X/fulltext https://www.thelancet.com/journals/lancet/article/PIIS2213-2... Looking at the drug cocktail that the patient received, this seems to be pretty heavy artillery: - methylprednisolone - moxifloxacin - lopinavir plus ritonavir - interferon - meropenem Holy shit, is this a recommended medication for severe Covid-19 cases?

Cantbekhan 7y ago
It seems this man was treated with lopinavir–ritonavir ... Unfortunately according to this recently published study, it seems inefficient against Covid19. https://www.nejm.org/doi/full/10.1056/NEJMoa2001282?query=featured_home https://www.nejm.org/doi/full/10.1056/NEJMoa2001282?query=fe... It also seems some EU countries are now stopping the use of lopinavir due to this study.
- jansan 7y ago
  I found this "Some centers and even national guidelines, such as those in Italy, have recommended treatment with lopinavir-ritonavir for patients with COVID-19 infection." Not sure what to make of this. Can this to some extent explain the huge differences in death rate between Italy and Germany? Source: https://www.medpagetoday.com/infectiousdisease/covid19/85499 https://www.medpagetoday.com/infectiousdisease/covid19/85499
  - Cantbekhan 7y ago
    As far as the netherlands are concerned, Lopinavir is now removed from their interim guidelines. The first line treatement is now hydroxichloroquine/chloroquine with maybe remdesivir for severe cases. Source (in Dutch): https://swab.nl/nl/covid-19 https://swab.nl/nl/covid-19 But yes in Italy the current guidelines (which are still dated 13 February still mention lopinavir). Source (in Italian): http://www.simit.org/medias/1569-covid19-vademecum-13-03-202.pdf http://www.simit.org/medias/1569-covid19-vademecum-13-03-202... It has also been removed from guidelines from Belgium: source (English) : https://epidemio.wiv-isp.be/ID/Documents/Covid19/COVID-19_InterimGuidelines_Treatment_ENG.pdf https://epidemio.wiv-isp.be/ID/Documents/Covid19/COVID-19_In... I think the odd case is France wich I think is still not having Chloroquine/Hydroxichloroquine in their guidelines as of today. I was not able to find the german guidelines.

ekianjo 7y ago

Criticism on study design during an emergency is fine, but still, we are not talking about some marginal level of efficacy here: https://www.medrxiv.org/content/10.1101/2020.03.16.20037135v1.full.pdf+html https://www.medrxiv.org/content/10.1101/2020.03.16.20037135v... > The proportion of patients that had negative PCR results in nasopharyngeal samples significantly differed between treated patients and controls at days 3-4-5 and 6 post-inclusion (Table 2). At day6 post-inclusion, 70% of hydroxychloroquine-treated patients were virologicaly cured comparing with 12.5% in the control group (p= 0.001). The effect size is huge, even considering the potential biases.

fabian2k 7y ago
One of the issues with the study is that they didn't use the clinical outcome as an endpoint, they just measured the virus concentration in the throat (and even that not properly for all cases as far as this HN post says). Huge effect size doesn't matter at all when the effect is not the correct one. There is a significant risk that this surrogate endpoint is not telling the true story as the virus migrates to the lung, measuring in the throat could be very misleading.
- ekianjo 7y ago
  Is there a reason to believe the viral load in the throat and the lungs would not follow the same trend? And you also forget to mention this (CQ and HCQ concentrate in certain organs): > It has been reported that oral absorption of CQ and HCQ in humans is very efficient. In animals, both drugs share similar tissue distribution patterns, with high concentrations in the liver, spleen, kidney, and lung reaching levels of 200–700 times higher than those in the plasma10. It was reported that safe dosage (6–6.5 mg/kg per day) of HCQ sulfate could generate serum levels of 1.4–1.5 μM in humans11. Therefore, with a safe dosage, HCQ concentration in the above tissues is likely to be achieved to inhibit SARS-CoV-2 infection. https://www.nature.com/articles/s41421-020-0156-0 https://www.nature.com/articles/s41421-020-0156-0
  - fabian2k 7y ago
    Yes, that's one aspect discussed in the podcast with Christian Drosten that is linked in the blog post. This is the relevant part: > We have a lot of experience. We have made the most precise description of an untreated patient cohort among the Munich patients. And at the Munich group, we saw how the virus concentration in both the throat and lungs behaved over time. And we can say that at the beginning of the disease the virus is in the throat and it goes away on its own through the - let's say - the first ten days of the disease. After that, many patients in the throat have little or only irregular evidence of the virus. But that has nothing to do with how the virus behaves in the lungs. The virus is then really replicative in the lungs, especially in severe cases. And we can also say what the patient has in his throat, it has nothing to do with how the clinical development of the disease continues, whether the patient quickly gets well or only goes through a difficult phase. So what is being measured in this entire clinical study has nothing to do with the outcome of the disease, with the symptoms, but is only an initial indicator of how the disease starts. For all patients, the virus concentration drops in the first week, but if you now imagine that the group being treated will be included a little later and the untreated group being included earlier in this study, it is in nature the thing that with this group that was later included - they are already further in eliminating the virus from the throat - that the virus then goes down in the throat, faster. This disappears faster because they have simply been in the course of the disease for a long time. Whether this is due to the fact that they are treated, cannot be said at all from this entire study. Perhaps it would have been so if the groups had been put together as here, but if they hadn't given them chloroquine, but some headache pill, the study would have been the same.

KillerRAK 7y ago

Nothing quite like a site titled "Better Science" with the disclaimer: "While I understand the basics of a clinical trial, I’d like to point out that I am no medical scientists. Most of the issues here were spotted by other people and I have linked to the sources." You cannot make this s@#t up! Put on your critical thinking caps folks -- there's a lot of bad info out there.

anonymous058 7y ago
A lot of people, for whatever reason, do not want hydroxychloroquine + azythromycin to work, and would instead prefer we endure 12-18 months of rolling lockdowns.
- frockington1 7y ago
  I've noticed that too. I think it might be due to all of the doomsday predictions going around on cable news scaring people. If you've just liquidated your 401k into cash at market lows, you're going to want reassurance that it was the correct thing to do
  - throwaway2048 7y ago
    Lets skip the "its the shorters that want you to fail!" conspiracy theories.
lanewinfield 7y ago
As soon as I read that line, I closed the window. Not worth it.
- jstanley 7y ago
  Why? I'd rather get information from a humble expert from a different field than from a braggart who thinks they're an expert.

DocSavage 7y ago

Regarding randomization, the HCQ + Azithromycin study showed good results despite the control group being 14 years younger. Sex was about equal so no male/female imbalance. It’s clear that older patients have worse outcomes, but this study measures viral load which also can change depending on the stage of the disease.

cycrutchfield 7y ago
There were 6 patients in that group. No mention of how they were selected. Some patients dropped out of the treatment group because they died or went to the ICU. These could affect the numbers significantly.

thdespou 7y ago

I've read that 2g of this drug can kill you.

Mountain_Skies 7y ago
So can 10g of caffeine. As a result, caffeine isn't distributed in ten gram doses.
frockington1 7y ago
2 grams of a lot of drugs will kill you. Most doses are in the 50-100 mg range for common drugs

lez 7y ago

Another anti-malaria drug, methylene blue had been proven to work against coronavirus in blood plasma in 2005 [1]. It is used in photodynamic therapy to selectively kill some viruses (see below) / bacteria (e.g. mycoplasma) [2]. When entering the bloodstream, it binds selectively to the nucleus of the viruses it is effective against. It's the same mechanism why it's effective as a dye to stain microbes under microscope. Methylene blue best absorbs light at 660nm wavelength, which at the same time penetrates into human tissues deeply. When light is absorbed, methylene blue disintegrates to harmless molecules while releasing reactive oxygene species, killing the virus. It is a very safe drug, so the same logic that bsaul mentioned could be applied, and therefore would be a responsible move. It is also beneficial to mitochondria and effective against fungus. [1] https://europepmc.org/article/cba/518857 https://europepmc.org/article/cba/518857 [2] https://www.sciencedirect.com/science/article/abs/pii/S1572100005000979 https://www.sciencedirect.com/science/article/abs/pii/S15721...

hprotagonist 7y ago
it also literally turns your bodily emissions blue, needs to be administered intravenously, and has some ugly side effects: Common side effects include headache, vomiting, confusion, shortness of breath, and high blood pressure.[1] Other side effects include serotonin syndrome, red blood cell breakdown, and allergic reactions.[1] Use often turns the urine, sweat, and stool blue to green in color.[3]
- lez 7y ago
  These side effects occur in extremely high doses, much much higher than the effective dosage. It doesn't need to be administered intravenously (only for methemoglobenia) - although more effective that way. serotonin syndrome, rbc breakdown and allergic reactions occur when you drink a glass of what few drops are enough. As said, it is extremely safe drug in low dosages (4-16 drops of 0.1% solution). Edit: Also see the Kevin Rose Show episode https://podcast.kevinrose.com/dr-peter-attia-longevity-compounds-fasting-supplements-and-more https://podcast.kevinrose.com/dr-peter-attia-longevity-compo... starting @ 1:16:20
tootie 7y ago

biolurker1 7y ago

I like facts. Article says only French study exists but at least a couple of other studies exist from China. I wish when someone makes a very important argument to check all internet sources.

stevespang 7y ago

Here we go, another naysayer. Unfortunately, all those waiting patiently for "confirmed results of double blind trials" will make up a significant percentage of those visiting the pearly gates by the time those trials are ever completed. Look, the risk is fairly low for chloroquine, mild side effects in a very well done Danish study were only ~15%, serious side effects were ~1.5%. Reported Side Effects to Chloroquine, Chloroquine plus ... academic.oup.com › jtm › article-pdf › jtm7-0079 Now, what's the risk of serious side effects/death from coronavirus for those over 70 years old ? Like >10%. And a recent report out of Hong Kong is stating that lung scarring from coronavirus is being found in all ages (radiological imaging), like 20 to 30% loss of lung function, shortness of breath reported by recovered patients just from fast walking - - - is that going to be permanent in all ages ? Are you willing to take that risk ? A glaring fact is that chloroquine / hydroxychloroquine have been on the WHO's list of essential medicines for decades . . . . why so, if they were too toxic to recommend ? Just like the rush on buying ammo, would you prefer to have "the likely treatment" before the problems comes to you - - or, would you prefer to fail to find it after all the shops and stores are completely sold out and the unemployed "zombies" are all over your property and smashing down your door while your family is cowering under the table screaming and crying for help ? I already got my supply of it, best of luck for all the naysayers. https://www.foxnews.com/health/florida-man-with-coronavirus-claims-malaria-drug-saved-life https://www.foxnews.com/health/florida-man-with-coronavirus-... https://video.foxnews.com/v/6143849011001 https://video.foxnews.com/v/6143849011001 BTW, what is your Gov't offering you right now in the way of proven drugs ? Nothing. All the while the rich in NY are reported in the news media as cashing in on favors to secure reservations for hospital beds in case they need them - - and buying ventilators . . . under the counter.

axguscbklp 7y ago

The numerous* stories that I have read recently about medical professionals writing themselves prescriptions for hydroxychloroquine so that they can have it available for themselves and their families suggests to me that the French trial is not the only reason to be hopeful about hydroxychloroquine's efficacy against COVID-19. Sure, medical professionals are not necessarily any kind of super-rational savants, but I think it's unlikely that all of the medical professionals who are trying to hoard hydroxychloroquine are being irrational hysterics. They might be engaging in ethically questionable acts by hoarding hydroxychloroquine, but that doesn't mean that they don't know what they're doing from a self-preservation standpoint. That said, it's not that I think they are necessarily trying to hoard hydroxychloroquine because they are convinced that it works - it's probably more that they want it on hand in case it turns out that it works. However, some of them may also have directly seen it help people, or may have heard or read about it helping. Given that hydroxychloroquine has already been used for, as I understand it, weeks in treating people ill with COVID-19, I am actually surprised that there is not more anecdotal evidence about its efficacy. But I probably have just not been reading in the right places. *Edit: I probably shouldn't have said "numerous stories", since "numerous" implies more than the number that I actually have seen.

brm 7y ago
If you're going to make these statements you should also share what you've been reading...
- axguscbklp 7y ago
  Sure. Here are a couple of places with sources. https://old.reddit.com/r/medicine/comments/flor5z/please_stop_prescribing_hydroxychloroquine_for/ https://old.reddit.com/r/medicine/comments/flor5z/please_sto... https://www.mahoningmatters.com/regional-news/ohio-doctors-accused-of-hoarding-potential-coronavirus-treatments-2188449 https://www.mahoningmatters.com/regional-news/ohio-doctors-a...
- DataWorker 7y ago
  https://www.washingtonpost.com/business/2020/03/20/hospitals-doctors-are-wiping-out-supplies-an-unproven-coronavirus-treatment/ https://www.washingtonpost.com/business/2020/03/20/hospitals...

jeffdavis 7y ago

It seems like the answer is "more science". Given how the virus is moving now, couldn't we have a pretty nice study completed in a few weeks?

roenxi 7y ago

Why are we so excited about the French trial? What about the Chinese treatment guidelines [0]? The Chinese recommend chloroquine phosphate. They've had more experience than anyone else in this area and have had time to conduct actual trials. The disease has a ~2-4 week course so it should take about that long to gather compelling evidence; and they've been dealing with it since January. The French are clever people, but we really should be looking to Asia for this information. People should be finding and quoting Chinese studies. [0] http://kjfy.meetingchina.org/msite/news/show/cn/3337.html http://kjfy.meetingchina.org/msite/news/show/cn/3337.html 10(b)(4)

klmadfejno 7y ago
The featured article claims that references to the supposed Chinese studies don't turn up anything. And that seems to be true. Here is the Chinese cited material from the French article: https://www.jstage.jst.go.jp/article/bst/14/1/14_2020.01047/_article https://www.jstage.jst.go.jp/article/bst/14/1/14_2020.01047/... It claims many clinical trials have been done in China that show chloroquine works. However... there's nothing to actually read with any data.
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Bhilai 7y ago

Related: Novartis commits to donate up to 130 million doses of hydroxychloroquine https://www.novartis.com/news/media-releases/novartis-commits-donate-130-million-doses-hydroxychloroquine-support-global-covid-19-pandemic-response https://www.novartis.com/news/media-releases/novartis-commit...

klmadfejno 7y ago

A lot of people are eager to say chloroquine is the answer and say, "forget the small details, look at that p-value!". But this article raises a bunch of important points. The important ones IMO are: 1) 6 / 26 of the individuals in the experimental group got removed from the stats because their condition got worse and the treatment ceased. One of them died. 2) The metric used to test the efficacy is viral load. You can get a negative on this and still have the disease. This is going to be a function of how long you've had the disease, which isn't controlled in the study. If you have a gripe with the author because they're not a medical scientist, read the peer review comments here: https://pubpeer.com/publications/B4044A446F35DF81789F6F20F8E0EE#2 https://pubpeer.com/publications/B4044A446F35DF81789F6F20F8E... They are easy to understand as a layman I feel. Other noteworthy takeaways: 1) The combination of HCQ and AZ was hyped as superior because all 6 patients did better. But looking at the data there is no significant difference in viral load outcomes between both drugs and just HCQ. 2) Many of the author's claims of statistical significance disappear if you use more conservative estimates for when people were supposed to be PCR positive except for Day 6 (now 0.01 instead of 0.001). 3) The paper turnaround was incredibly fast, with less than 24 hours for peer review. One of the authors of the paper is an editor of the journal in which it was published. Could be indicative of poor study controls. I hope this turns out to be useful. I would not be surprised if it did not. Regardless, the best case takeaway of THIS information does not inform us about how the drug performs in the most critical area (severe ICU patients). If you're a non-bio programmer please try to recognize that saying the current paper is good enough to justify mass distribution of chloroquine tablets to everyone is about on par with the cliche clueless product manager making bold decisions about how to move forward with your codebase despite having no clue how it works themselves.

gyrgtyn 7y ago

why is every study i've ever seen posted somewhere deeply flawed -in some way that is obvious to even non-experts?

pbreit 7y ago

Sure is a lot of energy going into trying to debunk this report and chloroquine in general. Is it because Trump mentioned it?

m0zg 7y ago
You're just witnessing the old joke IRL: If Trump could walk on water, the Left would complain that he can't swim. I'm not saying this works, but it does seem to me that for severely ill patients there's no harm in doing a large-ish field trial. Prophylactic use should receive more scrutiny.
- rplst8 7y ago
  Right. Like why not give it to those willing to try who can't get a vent in Italy.
  - m0zg 7y ago
    They do in fact "give it to those willing to try" in Italy, France, and China at a minimum. Probably elsewhere as well. Here in the US we're instead engaging in purely partisan bickering as to whether or not it should be available (which is not the same thing as pervasive use).
- TomMckenny 7y ago
  >You're just witnessing the old joke IRL: If Trump could walk on water, the Left would complain that he can't swim. The skepticism is due to false claims like "anybody that wants can get a test" [1] But as you say, maybe they shouldn't blame Trump since he says it's not his responsibility [2] Anyway, why do any treatment if the virus is a hoax[3], hype[4] and fake news[5] Or at worst, it is only one person coming from China and is totally under control [6] Certainly the president is not concerned at all about the White-house [7] And all this must be true because has has known it was a pandemic all along [8] [1] https://www.whitehouse.gov/briefings-statements/remarks-president-trump-tour-centers-disease-control-prevention-atlanta-ga/ https://www.whitehouse.gov/briefings-statements/remarks-pres... [2] https://youtu.be/NezEbDx4B9A?t=102 https://youtu.be/NezEbDx4B9A?t=102 [3] https://youtu.be/NezEbDx4B9A?t=57 https://youtu.be/NezEbDx4B9A?t=57 [4] https://twitter.com/realDonaldTrump/status/1236975196642390022 https://twitter.com/realDonaldTrump/status/12369751966423900... [5] https://twitter.com/realDonaldTrump/status/1237004509156642816 https://twitter.com/realDonaldTrump/status/12370045091566428... [6] https://www.cnbc.com/2020/01/22/trump-on-coronavirus-from-china-we-have-it-totally-under-control.html https://www.cnbc.com/2020/01/22/trump-on-coronavirus-from-ch... [7] https://youtu.be/NezEbDx4B9A?t=78 https://youtu.be/NezEbDx4B9A?t=78 [8] https://youtu.be/NezEbDx4B9A?t=109 https://youtu.be/NezEbDx4B9A?t=109

MisterBastahrd 7y ago

https://nypost.com/2020/03/19/sales-of-fish-tank-additive-skyrocket-after-studies-say-it-could-treat-coronavirus/ https://nypost.com/2020/03/19/sales-of-fish-tank-additive-sk... This is the kind of idiocy that pie-in-the-sky theatrical crap like this causes. People are going to end up seriously harming if not killing themselves by taking this stuff.

Avshalom 7y ago

https://thehill.com/policy/healthcare/489097-man-dies-after-taking-malaria-medication-in-effort-to-prevent-coronavirus https://thehill.com/policy/healthcare/489097-man-dies-after-... well that took what, two days?

max_ 7y ago

Chloroquine was banned years ago in my country due to its toxic effects (was making kids deaf amongst other things). Are its downsides worth the upsides when used as a COVID-19 treatment?

Zak 7y ago
The course of treatment is short, while some applications of chloroquine are long-term. The risk is likely considerably reduced.