32 ms·

Study: No evidence of efficacy of hydroxychloroquine in hospitalized patients

444 points by Cantbekhan 7y ago

Cantbekhan 7y ago
TLDR: French publication, non randomized 181 patients (hospitalized with pneumonia and O2 requirement) with control group (84 with HCQ, 97 without HCQ), no efficacy but adverse effects for some.
- Natsu 7y ago
  All the HQC results other than the heart problems (a known side effect) were slightly better, just not enough so to be statistically significant, I guess.
  - davrosthedalek 7y ago
    They are also quite likely correlated. If, by random chance, you have healthier people in one group than the other, it's likely they will have better outcomes in most categories.
- thierryzoller 7y ago
  According to Dr. Raoul - If the virus is no longer active indeed it doesn't help, but they already know that.
- orblivion 7y ago
  If this is accurate, perhaps the title could be edited to reflect the fact that it's a single study?
  - prox 7y ago
    It is, but these studies are done in a european setting, so more results may be coming.
jackfoxy 7y ago
Totally out of my depth here. I've been following Dr. Chris Martenson's daily covid-19 updates since late January. He is adamant this treatment is only effective in combination with zinc supplements.
- Donald 7y ago
  I’d look at clinical trials for zinc in other drug combinations and also alone. They’re not promising unless your population has a zinc deficiency.
- supercanuck 7y ago
  So why doesn't this guy setup clinical trials instead of providing non-confirmed medical advice on the daily? Probably cause he is lazy and more interested in selling and promoting himself than he is actually solving problems. This guy knows the scientific method, I assume. he knows that something needs to be observable and replicated. Instead, he is asking us to trust his brilliance on something where the side effect might be death and blindness??
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- deleted 7y ago
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- zimpenfish 7y ago
  This one? https://www.peakprosperity.com/about/ https://www.peakprosperity.com/about/ He doesn't seem to have many biomedical or pharmaceutical qualifications for pronouncing on what treatments may or may not work? Edit: Apparently he has a PhD in neurotoxicty (specifically "Acrylamide neurotoxicity: effect on neuronal growth cones and axonal fast transport") which does bolster his credentials.
- pjc50 7y ago
rurcliped 7y ago
See also https://news.ycombinator.com/item?id=22851998 https://news.ycombinator.com/item?id=22851998
julioo 7y ago
Point is that the study is done at the wrong stage, too late.
- IAmEveryone 7y ago
  Point is far too much time and money has been wasted chasing this particular goose just because your cult leader saw it as the silver bullet that could save his re-election. I hope we don’t waste additional bandwidth in the medical community just to disprove additional no-true-Scotsmen rewritings of history. Just this comment section already features two of them: “too late”, and “only in combination with zinc”.
  - adrianN 7y ago
    I don't think we wasted too much time and money on chloroquine. It looked promising in early trials. The proper thing to do is follow up on that. If it helped even just a little it would save literally thousands of lives. Having a well known drug be even slightly effective is pretty close to the best case scenario. Not following up on such leads would be stupid.
  - rhino369 7y ago
    The Trump thing is a huge distraction. Doctors in China and Europe were already singing its praises before Trump got involved. These tests aren't happening because Trump got excited about it.
  - TomatoTomato 7y ago
    It's a lot cheaper to test a known drug than to create a new one.
- beckingz 7y ago
  Isn't this at the same stage as the preliminary french trials that made headlines?
- deleted 7y ago
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- 7y ago
apendleton 7y ago
Personally I'm witholding judgment until the results of the PATCH trial (https://clinicaltrials.gov/ct2/show/NCT04329923 https://clinicaltrials.gov/ct2/show/NCT04329923) arrive, as it'll finally give us some decent statistical power, and be a full, double-blind RCT. It also has multiple study arms (health-care worker prophylaxis, home-quarantined early stage, hospitalized later-stage), so if it turns out that HCQ is effective but that by the time patients are hospitalized it's too late, as some are now suggesting, we should finally know with some degree of certainty.
- koheripbal 7y ago
  Yeah, the devil is really in the details about exactly when and how you administer it. Doctors are already saying that it's definitely no magic bullet, but they debate whether it is effective at a certain stage of illness. What I don't understand is why we're focusing so much on this specific drug when there are some great antivirals out thee that have a more effective theoretical mechanism of action. (eg Remdesivir)
  - simcop2387 7y ago
    It's being focused on in the news, but the others are also being tested. The big problem is like the GP raised, we need proper testing to really be able to say much about the ability of any of these drugs to help. [1] https://www.fiercebiotech.com/biotech/gilead-clinical-data-hint-at-efficacy-remdesivir-covid-19 https://www.fiercebiotech.com/biotech/gilead-clinical-data-h...
  - frgtpsswrdlame 7y ago
    Because this drug can be cheaply manufactured out of patent. Let's say Remdesivir is the only drug that works, it's basically an admission that Gilead is going to have us over a barrel.
    - munk-a 7y ago
      Only if we chose to let them bend us over said barrel? The US government could simply seize the patent if Gilead acted in a manner against the public good.
wnevets 7y ago
but think of the shareholders
- war1025 7y ago
  It costs something like $0.50 cents a pill.
  - AlexandrB 7y ago
    I think their point is that an available cure would allow the quarantine to end and re-start the economy.
  - drocer88 7y ago
    Does this include the liability costs?
Medicalidiot 7y ago
It was observed that between 7% and 28% of hospitalized have acute myocardial injury [1-4]. When one looks at Epocrates (database for drugs which is why I'm not linking anything here) the severe adverse reactions of hydroxycholoroquine include QT prolongation, cardiomyopathy, and torsade de pointes. Just to define some things here, QT prolongation is the time from your Q wave to your T wave, or the start of an electrical depolarization on your cardiac ventricles to repolarizations. QT elongation usually leads to cardiac arrest. Torsade de pointes is a syndrome where your cardiac ventricles beat so quickly that your heart paradoxically cannot fill up with blood potentially, and usually, leading to sudden cardiac death. Giving someone who has had essentially a heart attack (by definition COVID patients have elevated troponin which is the marker we use to assess if one has had a heart attack) is probably a bad idea so my question is: why would we celebrate a drug that has massive cardiac adverse effects as a side effect? Don't get me wrong I understand that there are drugs that are even worse. Cyclosporine is the first line immunosuppresant for kidney transplant. Do you know what one of the most common adverse effects of cyclosporine is? Kidney failure. But we don't know what is causing the kidney failure in a kidney transplant (rejection vs adverse effect) so we have to biopsy. Kidney biopsy is a very invasive procedure, FYI. My point is, maybe waiting for double blind placebo research here is the best case. Also, I made this exact same point on here a month ago and people told that they would take my dose if it came to that and at this point I will say go ahead. [1] https://www.ncbi.nlm.nih.gov/pubmed/32169400 https://www.ncbi.nlm.nih.gov/pubmed/32169400 [2] https://www.nejm.org/doi/full/10.1056/NEJMoa2004500 https://www.nejm.org/doi/full/10.1056/NEJMoa2004500 [3] https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.120.046941 https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.120.0... [4] https://jamanetwork.com/journals/jamacardiology/fullarticle/2763524 https://jamanetwork.com/journals/jamacardiology/fullarticle/...
- danans 7y ago
  > between 7% and 28% of hospitalized have acute myocardial injury So, for a younger (< 60) otherwise healthy person whose chance of death with covid is less than 1%, it would seem ill advised to take this medication at the onset of symptoms, unless the the disease itself causes similar or higher rates of heart damage.
w_t_payne 7y ago
Given that I need hydroxychloroquine to treat my rheumatoid arthritis, I'd like this hypothesis to be either proven or disproven as rapidly and as unambiguously as possible.
- AlexandrB 7y ago
  Because HCQ’s efficacy was briefly endorsed by a controversial political figure I fear that there’s no evidence in either direction will convince the true believers. This is now a political issue, like global warming. Hopefully someone is ramping up production so availability improves for those that actually need it.
  - loopz 7y ago
    The science providing data is apolitical. It just takes its due time.
    - munk-a 7y ago
      Yup - and said controversial political figure jumped on the guess before the science was in and heavily endorsed it - this is likely leading to widespread misuse of a drug which is know to cause extreme damage to organs including kidneys, livers and eyes when misdosed and taken in excess.
    - AlexandrB 7y ago
      The science may be apolitical, but the choice to accept or reject the science can depend on your politics. I think the anti-vaccination movement has shown that no amount of evidence is sufficient if someone is strongly attached to a belief for ideological reasons.
      - loopz 7y ago
        That is why science is not leadership.
    - t-writescode 7y ago
bretpiatt 7y ago
Lots of conflicting research happening[1], until we get multiple controlled trials we won't really know. Here's one that shows improvements. [1] French ~50 patient study that tried Control, Hydroxychloroquine, and Hydroxychloroquine + Azithromycin combo: https://www.mediterranee-infection.com/hydroxychloroquine-and-azithromycin-as-a-treatment-of-covid-19/ https://www.mediterranee-infection.com/hydroxychloroquine-an...
- war1025 7y ago
  > Lots of conflicting research happening That's my main take-away at this point. I have seen enough reports saying it worked, and enough saying it didn't that I believe the answer is probably somewhere in the middle. My understanding is the best guess for how it works is by keeping the viral infection from becoming serious enough to require hospitalization. Similar to how proper treatment of wounds early on keeps them from getting to the gangrene stage where you need amputation. Unfortunately, politics. So the Left wants it to be completely no use at all, and the Right wants it to be a miracle drug. Most of the population really probably just wants effective treatments if they end up getting sick.
  - the_af 7y ago
    I'm out of the loop here: why would any political faction not want an alleged cure to work? What's the goal here?
    - VBprogrammer 7y ago
      Trump all but prescribed it to the nation a miracle drug "a real chance to be one of the biggest game changers in the history of medicine". Questioning the wisdom of that, given how little we knew, is seen as a partisan attack on Trump.
    - winstonewert 7y ago
      Trump said positive things about it. The left wants Trump to be wrong about everything, so wants this it to fail. The right wants Trump to be right about everything, so wants it to work.
wyxuan 7y ago
This trial wasn't randomized, but a quasi randomized trial for HCQ whose preprint was leaked is here:https://www.dropbox.com/s/8b2govfsa6n0xbq/NEJM_Clinical%20Outcomes%20of%20Hydroxychlorquine%20in%20Patients%20with%20COVID19.pdf.pdf.pdf.pdf?dl=0 https://www.dropbox.com/s/8b2govfsa6n0xbq/NEJM_Clinical%20Ou... Study indicates that one adverse effect of HCQ (on top of not improving patient outcomes) is increased ventilator times.
- onlyrealcuzzo 7y ago
  From the paper: A total of 63 patients were included with 32 in the hydroxychloroquine arm. Hydroxychloroquine administration was associated with a need for escalation of respiratory support level compared to those that did not receive hydroxychloroquine at 5 days (p=0.013). The same findings were observed in a baseline-matched subgroup analysis. Absolute lymphocyte change in the hydroxychloroquine group was no different than supportive care alone (p=0.413). Hydroxychloroquine use trended towards worsening neutrophil-to-lymphocyte ratio compared to supportive care alone (+9.59 vs +1.58, p=0.51) as well as a higher risk for intubation (p=0.051).
  - layoutIfNeeded 7y ago
    p=0.413 p=0.51 So, basically coin toss?
    - onlyrealcuzzo 7y ago
      You overlooked the major finding of the study: > Hydroxychloroquine administration was associated with a need for escalation of respiratory support level compared to those that did not receive hydroxychloroquine at 5 days (p=0.013). > p = 0.013
    - jeremysalwen 7y ago
      > was no different than supportive care alone (p=0.413). Yes, exactly, p=0.413 corresponds to a coin toss, or as the authors of the paper put it "no different". The p=0.51 figure seems to be a typo in the abstract. If you read the content of the paper, it says > The hydroxychloroquine group also had a strong but not statistically significant trend towards worsening NLR (p=0.051). So I believe they just accidentally moved the decimal place, and they are correctly avoiding calling the result statistically significant, but it is close.
th3829 7y ago
That's because it's not hydroxychloroquine that helps them. It's Zinc. It just allows for much better absorption of the Zinc. Same can be achieved by combining Quercetin and Zinc.
firasd 7y ago
When the Covid crisis is over, one of the strangest sub- plots will have been the fracas around Hydroxychloroquine. Starting from medical practitioners worldwide adopting its usage in a ‘cargo cult’ way, mimicking what other doctors were doing, to Raoult’s low- quality study. Then people in Silicon Valley (notably Elon Musk) picking up the idea. Followed by the explosion in the political sphere, from Trump pushing it at the White House podium, to Indian PM Modi reversing an HCQ export ban for Trump, to French PM Macron talking it up. All the while HCQ remained unproven for Covid use, while people trying it got hurt by cardiac side- effects (and one couple in a prominent incident mistakenly took different chemicals with a similar name), and patients with other conditions ran out of HCQ due to shortages. Maybe HCQ will be part of the standard of care for Covid- 19 in the future, but it’s seeming less and less likely. Meanwhile it’s definitely not a miracle cure, so the frenzied advocacy and adoption of this medicine will turn out to have been a bizarre story. (I wrote this up here https://twitter.com/firasd/status/1250125344469708801 https://twitter.com/firasd/status/1250125344469708801)
- agumonkey 7y ago
  The recent reports about low benefits of HCQ didn't stop Raoult from appearing in a video about the state of HCQ and covid-19 in his clinic. Sadly he seems to be yet again using very wide statistics to justify his views (covid is of no importance compared to yearly stats [0]) and digress into political attacks (his past interactions with pharma labs that weren't conflict of interests). I still can't say if he's a low hanging troll [1] or if he's just so far above the pack that everybody else is braining wrong. That's also his motto... he likes to discuss disruption and paradigm shift in his classes and talks about how every past paradigm was considered gold standard and only people breaking the mold advanced the state of the art. [0] unsurprisingly Musk is also very fond of wide stats to justify his AutoPilot ~feature [1] his lab specializes in repurposing well studied compounds for new diseases.. seems like leveraging past efforts to get success (if I go full paranoia :)
  - _Wintermute 7y ago
    Even pre-covid, Raoult had a reputation for pumping out hundreds of really poor quality studies and making controversial public claims. It's a shame he's the one that's caught the attention of the general public, there's lots of good work going on with other potential treatments, but suddenly my social media is filled with armchair pharmacologists arguing about this one drug.
pcj-github 7y ago
Aside from these results, what is the proposed mechanism of benefit here? And why are we expecting a mechanism with hydroxychloroquine against this virus when essentially no small molecule therapies are effective against viruses in general?
- mcguire 7y ago
  Hydroxychloroquine is an immune suppressant and may help reduce the cytokine storm effect. How that interacts with the "you have to start it early" issue is unclear to me. And it might keep you from getting malaria while you have COVID19.
  - thepangolino 7y ago
    The way HCQ is by accumulating in cells. It inhibits the replication of viruses by interfering with endosome/lysosome trafficking or viral protein maturation during virion maturation. (basically stops the virus from replicating)
    - chasd00 7y ago
      and, correct me if i'm wrong, zinc helps take it with a grain of salt but https://www.snopes.com/fact-check/zelenko-669-coronavirus-patients/ https://www.snopes.com/fact-check/zelenko-669-coronavirus-pa...
      - rq1 7y ago
        No grain of salt needed, the chloroquine is a zinc ionophore.
      - souprock 7y ago
        With the right grain of salt, you get zinc. Suggestions: zinc acetate, zinc chloride, zinc citrate
    - mcguire 7y ago
      "The way HCQ is by accumulating in cells." The original study that set off this flap ran for a period of 6 days. I don't know that 6 days is long enough for significant accumulation. Beyond that, unless someone has published something significant that I haven't seen, any hypothesis on the drug's effect on coronavirus is pure speculation.
drummer 7y ago
Instead high doses of vitamin C have proven to be very effective.
capnrefsmmat 7y ago
It's important to interpret these results carefully: "no evidence of efficacy" does not imply evidence of no efficacy, and in fact the uncertainty in this study is quite large. The sample size is small enough that it would be very hard for this study to detect the effect of hydroxychloroquine unless that effect is very, very large. From the abstract: > In the HCQ group, 2.8% of the patients died within 7 days vs 4.6% in the no-HCQ group (3 vs 4 events, RR 0.61, 95% CI 0.13-2.89), and 27.4% and 24.1%, respectively, developed acute respiratory distress syndrome within 7 days (24 vs 23 events, RR 1.14, 95% CI 0.65-2.00). The relative risks and confidence intervals are the important numbers here. For example, the relative risk for death is 0.61, meaning the observed risk of death was lower for patients treated with hydroxychloroquine -- but the confidence interval is 0.13 to 2.89, meaning the data is consistent with anything from the risk being much smaller to the risk being much larger. Since there were only 3 deaths in the treatment group and 4 deaths in the control group, it's very hard to draw precise conclusions about death rates. I think we can interpret this result to mean that hydroxychloroquine doesn't have a miraculously large effect, but the evidence is weak. Other commenters are correct that large randomized trials will be more definitive. (disclaimer: I am a statistician, not a doctor)
- blakesterz 7y ago
  Would it be the same thing to do 1,000 small studies like this one as doing one LARGE study with 1000x more people? Would the results be considered just as useful?
  - lonelappde 7y ago
    Similar. That's called a "meta analysis" and tends to happen after many independent uncoordinated small studies have published.
    - emn13 7y ago
      Also, it's extremely hard to account for all kinds of biases and systematic errors in a meta-analysis. I'd take most meta-analyses, even by renowned statiticians, very, very skeptically. Teasing out small effects from samples that need corrections for lots of confounding factors, and then trying do combine many such results is next to impossible. If your effect is small enough that you need a meta-analysis in the first place, that's a warning sign. Some background: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0152719 https://journals.plos.org/plosone/article?id=10.1371/journal... (with perhaps more approachable explanation here https://www.talyarkoni.org/blog/2016/06/11/the-great-minds-journal-club-discusses-westfall-yarkoni-2016/ https://www.talyarkoni.org/blog/2016/06/11/the-great-minds-j... ) Obviously it's sometimes possible to do this right, but the reproducibiility crisis didn't appear out of nowhere; it's best to be wary of overly clever statistics; hard to know what you don't know.
jeffdavis 7y ago
Given the study's small sample size, it seems the only way it would have produced a conclusive result is if the effect size was huge (i.e. miracle cure). The study found some evidence of efficacy, but it was not significant given the sample size. A better headline would say something like: "study finds that HCQ is not a miracle cure for already-hospitalized covid-19 patients".
- mcguire 7y ago
  How much are you willing to pay for "not a miracle cure" on the basis of "eh, it can't hurt"?
  - deleted 7y ago
    [deleted]
  - jaywalk 7y ago
    Whether it works or not, HCQ is not a costly drug by any means.
  - jeffdavis 7y ago
    Your point doesn't really make sense, because the purpose of a study like this is not for making treatment decisions; it's for making research decisions. I don't see anything in the study that discredits HCQ as a potential treatment, and therefore it makes sense to keep researching.
- projektfu 7y ago
  What effect size would be a “game changer”?
- randcraw 7y ago
  No. This study found no evidence of effectiveness as a treatment for COVID-19 in patients who need it. A sample size of 20 is sufficient to satisfy a .05 statistical significance threshold that hydrochloroquine had even the slightest positive effect. In this population, it did not. All therapeutic drugs are developed using in vitro and pre-clinical (non human animal) treatment groups no bigger than 20. When a well controlled and randomized study comparng two groups that are each four times larger than 20, we have a VERY strong indication that this drug delivers not only too little effect to be a useful treatment for COVID-19, but it very likely delivered absolutely NO EFFECT AT ALL in hospitalized patients. Don't expect any reputable physician or scientist to dismiss this evidence. This is very bad news for the prospect for treating patients who need it using this drug -- those people who are likeliest to die or endure lasting harm. The other 80% of positive patients don't need any therapy except time.
mfer 7y ago
It's important to note that this study did not evaluate or note that Hydroxychloroquine had no effect on all people in all situations with COVID-19. This was a targeted study looking at a specific circumstance. The situation was "all adults in 4 French hospitals with documented SARS-CoV-2 pneumonia and requiring oxygen ≥ 2 L/min" So, adults who were not on oxygen are not included in the study. How does it pertain to them? That's not covered by this. It reads like it's saying people who are in bad shape and on ventilators did not have a positive impact by Hydroxychloroquine. This still leaves open questions like, can the use of Hydroxychloroquine lower the rate of needing to get on a ventilator. I look forward to someone reproducing this study and looking into the other areas.
deleted 7y ago
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edoo 7y ago
What a joke. An emulated trial only in patients already requiring oxygen. How about this http://covexit.com/professor-didier-raoult-releases-the-results-of-a-new-hydroxychloroquine-treatment-study-on-1061-patients/ http://covexit.com/professor-didier-raoult-releases-the-resu... I'm taking the HQZ cocktail at first diagnosis even if I have to doctor shop.
sheinsheish 7y ago
I don’t understand who gets to decide and how, which of these people receive / don’t receive a specific treatment. I’ve always loved medical studies, but now the crisis got me to thinking about the moral decision (playing god?)
- CydeWeys 7y ago
  The answer is, by and large, doctors. Within the hospitals they really do have the power of life and death, deciding who gets treatment when supplies are thin. Generally the decisions are made using the heuristic of "With this limited stock of X, who should we give it to to save the maximum possible number and quality of lives?" It's not playing god, it's just making rational decisions in times of scarcity. That's something humans do constantly, no god necessary.
- DanBC 7y ago
  You might be interested in this letter from the BMA: https://www.bma.org.uk/media/2283/bma-ethics-guidance-and-age-and-disability-statement-april-2020.pdf https://www.bma.org.uk/media/2283/bma-ethics-guidance-and-ag... > This note addresses in more detail the relationship between our guidance and those patients who are elderly or who have disabilities. It emphasises that neither age nor disability are in themselves relevant criteria for making decisions about treatment. This follows on from widespread (and perhaps misleading) reporting about a tool. This tool has NHS branding, but it doesn't appear to have come from NHS_England+Improvement. http://prod-upp-image-read.ft.com/765d3430-7a57-11ea-af44-daa3def9ae03 http://prod-upp-image-read.ft.com/765d3430-7a57-11ea-af44-da...
bcrosby95 7y ago
And to put this interpretation into perspective, people that need this drug for diseases that it has proven to have a large effect on are losing access to it because it may or may not help with COVID-19.
- beaner 7y ago
  Is there a source for this claim?
  - DangerousPie 7y ago
    There were lots of newspaper articles a few weeks ago about lupus patients struggling to access HCQ. Eg: https://www.nytimes.com/2020/04/06/opinion/coronavirus-hydroxychloroquine-lupus.html https://www.nytimes.com/2020/04/06/opinion/coronavirus-hydro... or https://www.washingtonpost.com/politics/2020/04/13/how-false-hope-spread-about-hydroxychloroquine-its-consequences/ https://www.washingtonpost.com/politics/2020/04/13/how-false...
  - eesmith 7y ago
    Wikipedia links to two WaPo articles at https://en.wikipedia.org/wiki/Hydroxychloroquine#Regulatory_approval https://en.wikipedia.org/wiki/Hydroxychloroquine#Regulatory_... Guardian article - https://www.theguardian.com/world/2020/mar/27/vital-drug-people-lupus-coronavirus-covid-19-link-hydroxychloroquine https://www.theguardian.com/world/2020/mar/27/vital-drug-peo... . It cites someone from Lupus UK. Their page at http://www.lupusuk.org.uk/uk-azathioprine-supply/ http://www.lupusuk.org.uk/uk-azathioprine-supply/ says "we have received reports from a number of people with lupus who have been unable to fulfil their prescription of azathioprine" and that "stocks are in the process of being replenished and should be available in the UK in mid-April". Comment from an HN'er: "For several weeks my mother hasn't been able to fill her regular prescription for hydroxychloroquine that has been an important part of managing her lupus for >30 years." - https://news.ycombinator.com/item?id=22793293 https://news.ycombinator.com/item?id=22793293
    - beaner 7y ago
      Is this shortage universal? Have there been shortages before, either universal or local? Is there evidence that this particular local shortage is due specifically to coronavirus demand? It may be that the answer to these questions is "yes," but that answer seems to be being assumed right now.
williesleg 7y ago
Hey, if you don't want to take it, don't. Simple as that.
pdonis 7y ago
A useful compilation of information on HCQ and COVID-19: https://docs.google.com/document/d/1O6Cls-Oz2ZAgJuyDbnICEGjMvQPEyM-aaXARUomR9Ww/edit https://docs.google.com/document/d/1O6Cls-Oz2ZAgJuyDbnICEGjM...
DevKoala 7y ago
The sample was 185 patients. There are anecdotal evidences that support the medicine which claim to have more, the letter came from a French doctor too. The study is discouraging for sure though.
twomoretime 7y ago
It really bothers me how hard both citizens and officials seem to be wanting Chloroquine to fail all because somebody they didn't like endorsed it publicly. Can't let him have that win, right? Like children. The original studies that showed promise used combinations of Chloroquine, Azithromycin, and or zinc, and there is a speculated pathway by which these drugs interact to interfere with COVID replication. This study only looked at HCQ. This kind of partisan, childlike pettiness is dangerous to all of us - what if Chloroquine works but we overlooked it because a couple shitty papers told us what we wanted to hear? Was it appropriate to tweet about? Debatable. It is a presidents job to keep his people hopeful when possible, and this drug cocktail was in multiple (admittedly not perfect) papers at the time of the tweet. People need to be more objective when evaluating statements made by the president. That doesn't mean you have to like him.
- nkozyra 7y ago
  I think there's a bunch of strawmen here. It's disingenuous to say that people who found [said person]'s comments to be a bad idea want it to fail. Indeed, if that person had come up and said "there's a lot of promising treatments, such as ..." or "the experts are telling us that some studies involving [x, y, z] are showing some positive signs" or something of that ilk, nobody would have cared. Instead, the person multiple times touted something that is to date unproved. People find that irresponsible for a number of reasons, not least of which that there are legitimate users who need this and it's now in short supply. So what people are protesting is someone not waiting for medical science and just causing noise. Like many things, this person could have handled this all more responsibly.
  - twomoretime 7y ago
    >https://youtu.be/oWQjWepaDv0 https://youtu.be/oWQjWepaDv0 "Very promising early results". >https://www.google.com/search?q=trump+tweet+chloroquine&prmd=insv&source=lnms&tbm=isch&sa=X&ved=2ahUKEwjvzOjehOvoAhVICc0KHcxyD8gQ_AUoAXoECAwQAQ&biw=412&bih=556&dpr=2.63#imgrc=sU_DAlax8JfVaM https://www.google.com/search?q=trump+tweet+chloroquine&prmd... "Have a real chance to be one of the biggest game changers" Meanwhile the media response has been universally lamenting that a president would "tell people" [he didn't] to take this drug. How many outlets jumped on the single chloroquine phosphate overdose as proof of the president's responsibility? I encourage you to search "Trump" and "chloroquine" and find me a single headline that doesn't tear into Trump. Like most people, your views have been warped by headlines and op-eds being touted as "news." The fact that the president acts like a child doesn't mean our news should too. The petty editorialization of the daily briefings are an excellent example - the media's job in such a case is to be an objective first source - not to force their point of view through adversarial headlines that change every 5 seconds and "fact checking" only his alleged untruths. But this is where the majority of Americans get their news. It's shameful. Edit: hell, look at this absolutely ridiculous headline at the top of the CNN "fact check" page: "Fact check: Trump denies saying another thing he said and makes more false claims at coronavirus briefing" What kind of headline is that? Is anyone competent left at CNN? The media no longer deserves the soft power it wields. They lost that privilege when they strayed so far from any semblance of objectivity.
hartator 7y ago
> documented SARS-CoV-2 pneumonia and requiring oxygen ≥ 2 L/min to emulate a target trial aimed at assessing the effectiveness of HCQ at 600 mg/day Well hydroxychoroquine is only useful before ventilators are needed (it attacks the full lungs) and is actually detrimental - we know that - after by its nature. What kind of bad science is this study where you actually push patients through a known dangerous path to try to prove the non efficiency of a potential treatment.
- ejstronge 7y ago
  >Well hydroxychoroquine is only useful before ventilators are needed (it attacks the full lungs) and is actually detrimental - we know that - after by its nature. I’m worried that this has totally left the realm of science and is just pure politics... there is no evidence for a ‘magic window’ for HCQ in COVID-19 treatment, or any solid evidence of a positive role. Secondly, having supplemental oxygen is not the same as being on a ventilator. I imagine most hospitalized COVID patients need oxygen (otherwise, they could be managed at home). I hope we all avoid making comments (or even accepting comments) about medicine without either critical, independent study or background knowledge.
mcguire 7y ago
While we're here, "Traditional Chinese Medicine in the Treatment of Patients Infected with 2019-New Coronavirus (SARS-CoV-2): A Review and Perspective" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7098036/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7098036/) Hey, it can't hurt and it might help. China has had one of the best recoveries from the pandemic.
- forgingahead 7y ago
  Thanks for sharing this, not sure why you're getting downvoted. TCM has its place, Artemisia Annua has been used as an anti-malarial treatment as well for hundreds of years, and again, is cheap, available, and side effects are known. I've had anecdotal experience that it's helpful for milder coronavirus symptoms.
  - AlexandrB 7y ago
    > Thanks for sharing this, not sure why you're getting downvoted. Because TCM is - charitably - pseudoscience. Many of its remedies involve grinding up endangered animals into concoctions that have no plausible mechanism of treating the thing they're meant to treat. > I've had anecdotal experience that it's helpful for milder coronavirus symptoms. I have anecdotal experience that my microsorium musifolium plant has been effective in preventing coronavirus infection in my household. Unfortunately, just like your statement, this doesn't qualify as evidence and shouldn't be used to make public health decisions.
    - forgingahead 7y ago
      You are mindreading my comment of "TCM has its place" and are wrongly confusing it in your own imagination of "used to make public health decisions". Please don't do that, it's insulting to folks trying to have open discussions, and it also makes you, the mindreader, stressed and anxious about things that are not happening.
- perardi 7y ago
  I cannot tell if you are purposefully trolling, or this is sincere. Regardless, let's wade in… 1. That's not's a study. That's not a metareview. That's a puff piece by people who have a strong, strong self-interest in promoting TCM, because they want to keep their department chairs. 2. Oh heck, I'll just quote the entire last paragraph: "The safety of TCM in the treatment of emerging coronavirus diseases was not included in the observation on SARS patients. It was reported that some herbs used in TCM contain nephrotoxins and mutagens, while the toxicological features of the most of Chinese herbal medicines remain to be fully understood. Furthermore, herbs used in TCM can mimic, or magnify, or oppose the effect of conventional medicines. Thus, the safety of TCM used in treatment of emerging coronavirus infections should be carefully evaluated. It is particularly important to avoid toxicity or interfere with the efficacy of conventional treatment caused by herb-drug interaction." So, in conclusion, we don't know if this works, and this stuff may be toxic, and it may have drug interactions, and oh by the way there's no quality control on this so you have no idea what's in the medications. Might as well recommend acupuncture and getting your chakras aligned, couldn't hurt! (Probably less of a chance it hurting than taking a wild dose of unregulated herbal supplements.)
forgingahead 7y ago
This whole debate is insane to me -- some people that so-called "experts" don't like mentioned HCQ as a possible treatment for coronavirus, and we've ended up in some bizarro world where everyone is shouting and fingers are being pointed over something that really shouldn't be controversial or perceived as some sinister plot to destroy clever society. 1. HCQ has been used for many decades 2. The side effects are generally known 3. It may have a positive impact on COVID-19, and it may not. 4. Nobody is suggesting long term high doses for anyone, COVID patients or otherwise. 5. If people are severe patients of COVID-19, this should certainly be tried as a treatment as long as the patient (or immediate family) is briefed on the potential side effects. The alternative, potential death, makes this a worthy discussion for a doctor/patient to have, with families being allowed to err on the side of right-to-try. HCQ is cheap, available, and has been used for decades. The fact that "no evidence HCQ works!!" has 200 points of upvotes and counting when the sample size for this study is 181 patients only just shows how high the temperature has become. Everyone just calm down. As capnrefsmmat has eloquently pointed out, "absence of evidence" does not mean "evidence of absence". If you enjoy the thrill of debates for debates sake, here are other potential topics for you: Whether masks are effective, condoms, seatbelts, helmets, or even parachutes[0]: [0]https://www.ncbi.nlm.nih.gov/pmc/articles/PMC300808/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC300808/ Favourite part: Results We were unable to identify any randomised controlled trials of parachute intervention. Conclusions As with many interventions intended to prevent ill health, the effectiveness of parachutes has not been subjected to rigorous evaluation by using randomised controlled trials. Advocates of evidence based medicine have criticised the adoption of interventions evaluated by using only observational data. We think that everyone might benefit if the most radical protagonists of evidence based medicine organised and participated in a double blind, randomised, placebo controlled, crossover trial of the parachute.
- DangerousPie 7y ago
  1. Not for coronaviruses. 2. They are known but they are by no means mild. A trial in Brazil just got aborted due to severe heart problems. 3. So does almost everything. If that's your threshold for taking a drug then I have a lot of homeopathic remedies to sell you! 4. Actually the doses given for COVID are often higher. Not sure what long-term has to do with anything. 5. That assumes that the risk of side effects is zero. It's not. Also, there is an opportunity cost to taking HCQ instead of something else. I totally agree with you that we should do proper trials on this and see what happens. But right now there is zero evidence that it actually works, and some (admittedly low-quality) evidence that it might not.
jonplackett 7y ago
Why is it taking so long to do a big study on this? There are so many sick people and it’s a cheap drug and only takes a week Or 2 to see if it works. Can someone please just do a Really large trial, like, 2 weeks ago so we can put this to bed one way or the other.
stevespang 7y ago
Very possible that once a patient has deteriorated to needing hospitalization with O2, it may be too late for hydroxychloroquine to be of benefit - - the virus has already destroyed the lungs.
m0zg 7y ago
Wow, several HCQ stories on the front page. Means it's probably going to be proven effective soon.
Techies4Trump 7y ago
Sample size is far too small. If anything this study shows (albeit with small numbers) that HCQ doesn't make things worse. But I have a feeling HCQ will be found to be effective. Big pharma have a lot of $$$ to make from their vaccine though.
Khelavaster 7y ago
This study is basically garbage. It applies to people who're so damaged from Covid they need at least 2 liters of oxygen per minute. It studies treatment with pure hydroxychloroquine--no zinc, no azithromycin/doxycycline/ivermectin. Hydroxychloroquine. Patients who get their treatment from doctors less fraudulent than the authors of this study almost certainly see better outcomes.
tgafpc2 7y ago
"collected data to emulate a target trial" I take it this means it's not an actual clinical trial, just a virtual trial? What's the point? Of all the people that died, none were saved by the drug. Sounds like an insurance ad.
DoreenMichele 7y ago
This study is specifically about patients sick enough to be put on oxygen. The top ranked comments don't seem to address that detail. Some thoughts: My understanding is this is a powerful alkaloid. My experience has been that similar compounds can help combat inflammation. They also can work to help kill infection at times. By the time people with Covid19 need oxygen, inflammation doesn't seem to be the primary problem. So I wouldn't think it would be particularly helpful at that point. Ventilators get prescribed in part on the assumption that inflammation in the lungs is a major impediment to getting sufficient oxygen. Ventilators are failing at a shockingly high rate, with a death rate up around 80% or so. Some doctors are moving away from ventilators because the death rate is so high. I spoke recently with a researcher who suggested impaired vasodilation was a possible explanation for the reports of low oxygen combined with a surprising lack of pneumonia and inflammation in some cases and that makes a lot of sense to me. The mechanism causing low oxygen does not appear to be the obvious answer of "lung inflammation and pneumonia." That doesn't mean this drug can't play a meaningful role at some stage. It mostly means it's not the magic bullet solution for advanced cases that they were hoping for. This in no way surprises me because the things it actually treats do not appear to be the cause of low oxygen in advanced covid19 cases.
- firasd 7y ago
  You might find this thread interesting (“There's a growing body of data to strongly suggest #COVID19 predisposes to both venous and arterial thromboembolism due to excessive inflammation, hypoxia, immobilization and diffuse intravascular coagulation.”) https://twitter.com/scottgottliebmd/status/1250069609581031428?s=21 https://twitter.com/scottgottliebmd/status/12500696095810314...
  - DoreenMichele 7y ago
    Thank you. It is interesting stuff and fits with some of my impression that they are overlooking important blood-related issues. Anemia (a blood disorder) is also a cause of low oxygen. That's not exclusive to lung function. Glad to see some doctors are working on that angle. (crosses fingers, hopes for better treatments soon)
thanatropism 7y ago
There are dozens upon dozens of speculative treatments. Interactome research is churning out candidates. I think the people have a right to know about cloroquine, since it became such a political point. But n=181 is not that small.
mekoka 7y ago
I think it's too bad that this drug has been so politicized. It's really unfortunate that its two original and most prominent champions are people that are so disliked. So many people spoke up (maybe prematurely) against it in a knee-jerk reaction to its advocates. Now many act as if they're more concerned about being right to ridicule the claims all along, than they are about whether the drug is actually helpful in fighting COVID-19. Which, for the rest of us without a stake in their stupid political feuds, is all that matters. And because of this idiotic battle of the egos we could be passing on something useful. So here we all are, hanging by the edge of our seats, waiting for definitive proof that HCQ does not help in fighting COVID-19 and we keep getting these half-assed reports, seemingly more aimed at pushing a narrative than to present (or eliminate) an option in a fight. One of the latest examples is the account of Rita Wilson (wife of Tom Hanks) who survived what seems like a difficult case of COVID-19 and shared her experience with the media: she felt very tired, extremely achy, uncomfortable, didn't want to be touched, on the ninth day her fever climbed up to 102 and she had chills like she'd "never had before" (her words), she lost her sense of taste and smell. Then she was given chloroquine, her fever broke (it's not clear how long after). She goes on to warn against the "extreme" (her word) side-effects she attributes to chloroquine: she was completely nauseous, she had vertigo, she could not walk and her muscles felt very weak. She then concludes that although her fever broke after been given chloroquine, she doesn't know if it helped or if it was just time, which is fair. What do you imagine the headline for that story should be? Well, to save you the trouble, most read like this Rita Wilson warns against "extreme" side-effects of chloroquine. Are HCQ/CQ effective? We're still sitting here like idiots not knowing. If they are, should they be taken carelessly? Definitely not, we already got that, thanks, but that is not the point. We can't afford to have an "all or nothing" mindset with these drugs as we did with masks. Simply proclaiming that HCQ is useless because it is shown not to reduce viral load is just the best way to pass on some other ways it might be helping. If it is shown to have other palliative effects that actually help patients in their fight, such as reducing inflammation or helping cope with high fever long enough for your immune system to do the job, it's not nothing. It's information. It's an option.
krn320 7y ago
There is an obvious pushback on hydroxychloroquine. Not enough money to be made so other "solutions" are preferred. Something that was used for more than 50 years is being tested for safety? What a joke. I'm sure when vaccines arrive they'll be "safe and effective" and used all around the world from day one...
krn320 7y ago
There is an obvious pushback for hydroxychloroquine. Something that was used for more than 50 years should've been widely adopted by now but there is not enough money to be made (and let's not forget political issues). I'm sure when vaccine arrives it'll be "safe and effective" and widely used around the world from day one - no questions asked.
cameldrv 7y ago
The study is way underpowered (too small a sample). Based on the raw numbers, the HCQ group had less deaths and less ICU admissions, but the numbers we're talking about are 3 vs. 4 deaths and 16 vs. 21 ICU admissions (group sizes were different). These numbers simply aren't enough to make a determination one way or the other. On mortality, the 95% confidence interval allows for a range of HCQ reducing death rates by 87% up to it increasing death rates by 2.9x.
droithomme 7y ago
Hm, the pseudo-study (it was a after the fact data review) found a near halving of mortality rates in the HCQ group. Yet that is described as no evidence of efficacy. Odd.
dfsajlkjadfalk 7y ago
Open America Now!
projektfu 7y ago
I know this study doesn’t put anything to bed, but one has to understand that the basis for the HCQ and CQ (+/- zinc) thing is the same as x kills cancer in vitro. Then, you get a motivated researcher who publishes a single arm study of essentially OK patients claiming zero deaths. Game changer? We’ll see. But I imagine there are hospitals that are already using this as a first line treatment and there’s no positive reviews from the front line. Beyond that, we do have the ability to perform small sample studies (cf. Student) and decide whether we’re headed in the right direction. Are we in a lull in statistics where we can’t even use statistics to guide future research?
maa5444 7y ago
italian doctor proposed a working cure .... his name is molinari
giardini 7y ago
full title "No evidence of clinical efficacy of hydroxychloroquine in patients hospitalised for COVID-19 infection and requiring oxygen:..." from the article: "We used data collected from routine care of all adults in 4 French hospitals with documented SARS-CoV-2 pneumonia and requiring oxygen ≥ 2 L/min to emulate a target trial aimed at assessing the effectiveness of HCQ at 600 mg/day... This study included 181 patients with SARS-CoV-2 pneumonia; 84 received HCQ within 48 hours of admission (HCQ group) and 97 did not (no-HCQ group). The median age of patients was 60 years ..." "...[Patients were from] four French tertiary care centres providing care to patients with COVID-19 pneumonia. Adult patients were eligible in this study if they were aged between 18 years and 80 years, had PCR-confirmed SARS-CoV-2 infection, and required oxygen by mask or nasal prongs (corresponding to a WHO progression score of 5)." "Among the 181 patients eligible for analysis, 84 received HCQ within 48 hours of admission and 97 did not (although 8 of them did receive HCQ later on)." So, first of all, these patients were infected with Covid-19 _days_ prior and now had progressed to pneumonia. The up to two-day delay in the administration of HCQ after admittance to the study is disheartening. I am surprised that, despite the experimentors selecting an elderly, pneumonic, oxygen-dependent cohort in advanced stages of the disease, these patients did as well as they did. Its a credit to the human body. But timing is everything... Once a Covid-19 patient has developed pneumonia, it is too late for hydroxychloroquine to affect the Covid-19 virus' replication process significantly. The patient's body is saturated with the virus. In a patient who has developed pneumonia the disease has progressed to a second phase wherein the virus and other opportunistic pathogens (e.g., bacteria) attack the lungs and other tissue. Antibiotics may help at this point. But it is quite clear that the patients in this study arrived too late to gain any benefit from hydroxychloroquine which, when coupled with zinc sulfate, slows or halts viral replication _early_ in the disease, delays or halts the virus' progress and allows the body time to develop an immunological response to the virus. The study's conclusion states explicitly that " These results ... do not support the use of HCQ in patients hospitalised for a documented SARS-CoV-2 pneumonia." So, the trick is to treat _early_ with HCQ+zinc sulfate+azithromycin.
newintellectual 7y ago
They apparently omitted a critical component: zinc.
cheese4242 7y ago
400+ points on Hackernews for... this? There have been a variety of studies and reports, both for and against, the use of hydroxychloroquine. Is there any reason this particular study is so highly upvoted? Or is this just an attempt to dunk on Trump for suggesting the drug showed promise?
- tigershark 7y ago
  It’s a study with a fairly high number of participants and it has not been conducted by the controversial author of the flawed first study.

444 points by Cantbekhan 7y ago

TLDR: French publication, non randomized 181 patients (hospitalized with pneumonia and O2 requirement) with control group (84 with HCQ, 97 without HCQ), no efficacy but adverse effects for some.

Natsu 7y ago
All the HQC results other than the heart problems (a known side effect) were slightly better, just not enough so to be statistically significant, I guess.
- davrosthedalek 7y ago
  They are also quite likely correlated. If, by random chance, you have healthier people in one group than the other, it's likely they will have better outcomes in most categories.
thierryzoller 7y ago
According to Dr. Raoul - If the virus is no longer active indeed it doesn't help, but they already know that.
orblivion 7y ago
If this is accurate, perhaps the title could be edited to reflect the fact that it's a single study?
- prox 7y ago
  It is, but these studies are done in a european setting, so more results may be coming.

jackfoxy 7y ago

Totally out of my depth here. I've been following Dr. Chris Martenson's daily covid-19 updates since late January. He is adamant this treatment is only effective in combination with zinc supplements.

Donald 7y ago
I’d look at clinical trials for zinc in other drug combinations and also alone. They’re not promising unless your population has a zinc deficiency.
supercanuck 7y ago
So why doesn't this guy setup clinical trials instead of providing non-confirmed medical advice on the daily? Probably cause he is lazy and more interested in selling and promoting himself than he is actually solving problems. This guy knows the scientific method, I assume. he knows that something needs to be observable and replicated. Instead, he is asking us to trust his brilliance on something where the side effect might be death and blindness??
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zimpenfish 7y ago
This one? https://www.peakprosperity.com/about/ https://www.peakprosperity.com/about/ He doesn't seem to have many biomedical or pharmaceutical qualifications for pronouncing on what treatments may or may not work? Edit: Apparently he has a PhD in neurotoxicty (specifically "Acrylamide neurotoxicity: effect on neuronal growth cones and axonal fast transport") which does bolster his credentials.
pjc50 7y ago

rurcliped 7y ago

See also https://news.ycombinator.com/item?id=22851998 https://news.ycombinator.com/item?id=22851998

julioo 7y ago

Point is that the study is done at the wrong stage, too late.

IAmEveryone 7y ago
Point is far too much time and money has been wasted chasing this particular goose just because your cult leader saw it as the silver bullet that could save his re-election. I hope we don’t waste additional bandwidth in the medical community just to disprove additional no-true-Scotsmen rewritings of history. Just this comment section already features two of them: “too late”, and “only in combination with zinc”.
- adrianN 7y ago
  I don't think we wasted too much time and money on chloroquine. It looked promising in early trials. The proper thing to do is follow up on that. If it helped even just a little it would save literally thousands of lives. Having a well known drug be even slightly effective is pretty close to the best case scenario. Not following up on such leads would be stupid.
- rhino369 7y ago
  The Trump thing is a huge distraction. Doctors in China and Europe were already singing its praises before Trump got involved. These tests aren't happening because Trump got excited about it.
- TomatoTomato 7y ago
  It's a lot cheaper to test a known drug than to create a new one.
beckingz 7y ago
Isn't this at the same stage as the preliminary french trials that made headlines?
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apendleton 7y ago

Personally I'm witholding judgment until the results of the PATCH trial (https://clinicaltrials.gov/ct2/show/NCT04329923 https://clinicaltrials.gov/ct2/show/NCT04329923) arrive, as it'll finally give us some decent statistical power, and be a full, double-blind RCT. It also has multiple study arms (health-care worker prophylaxis, home-quarantined early stage, hospitalized later-stage), so if it turns out that HCQ is effective but that by the time patients are hospitalized it's too late, as some are now suggesting, we should finally know with some degree of certainty.

koheripbal 7y ago
Yeah, the devil is really in the details about exactly when and how you administer it. Doctors are already saying that it's definitely no magic bullet, but they debate whether it is effective at a certain stage of illness. What I don't understand is why we're focusing so much on this specific drug when there are some great antivirals out thee that have a more effective theoretical mechanism of action. (eg Remdesivir)
- simcop2387 7y ago
  It's being focused on in the news, but the others are also being tested. The big problem is like the GP raised, we need proper testing to really be able to say much about the ability of any of these drugs to help. [1] https://www.fiercebiotech.com/biotech/gilead-clinical-data-hint-at-efficacy-remdesivir-covid-19 https://www.fiercebiotech.com/biotech/gilead-clinical-data-h...
- frgtpsswrdlame 7y ago
  Because this drug can be cheaply manufactured out of patent. Let's say Remdesivir is the only drug that works, it's basically an admission that Gilead is going to have us over a barrel.
  - munk-a 7y ago
    Only if we chose to let them bend us over said barrel? The US government could simply seize the patent if Gilead acted in a manner against the public good.

wnevets 7y ago

but think of the shareholders

war1025 7y ago
It costs something like $0.50 cents a pill.
- AlexandrB 7y ago
  I think their point is that an available cure would allow the quarantine to end and re-start the economy.
- drocer88 7y ago
  Does this include the liability costs?

Medicalidiot 7y ago

It was observed that between 7% and 28% of hospitalized have acute myocardial injury [1-4]. When one looks at Epocrates (database for drugs which is why I'm not linking anything here) the severe adverse reactions of hydroxycholoroquine include QT prolongation, cardiomyopathy, and torsade de pointes. Just to define some things here, QT prolongation is the time from your Q wave to your T wave, or the start of an electrical depolarization on your cardiac ventricles to repolarizations. QT elongation usually leads to cardiac arrest. Torsade de pointes is a syndrome where your cardiac ventricles beat so quickly that your heart paradoxically cannot fill up with blood potentially, and usually, leading to sudden cardiac death. Giving someone who has had essentially a heart attack (by definition COVID patients have elevated troponin which is the marker we use to assess if one has had a heart attack) is probably a bad idea so my question is: why would we celebrate a drug that has massive cardiac adverse effects as a side effect? Don't get me wrong I understand that there are drugs that are even worse. Cyclosporine is the first line immunosuppresant for kidney transplant. Do you know what one of the most common adverse effects of cyclosporine is? Kidney failure. But we don't know what is causing the kidney failure in a kidney transplant (rejection vs adverse effect) so we have to biopsy. Kidney biopsy is a very invasive procedure, FYI. My point is, maybe waiting for double blind placebo research here is the best case. Also, I made this exact same point on here a month ago and people told that they would take my dose if it came to that and at this point I will say go ahead. [1] https://www.ncbi.nlm.nih.gov/pubmed/32169400 https://www.ncbi.nlm.nih.gov/pubmed/32169400 [2] https://www.nejm.org/doi/full/10.1056/NEJMoa2004500 https://www.nejm.org/doi/full/10.1056/NEJMoa2004500 [3] https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.120.046941 https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.120.0... [4] https://jamanetwork.com/journals/jamacardiology/fullarticle/2763524 https://jamanetwork.com/journals/jamacardiology/fullarticle/...

danans 7y ago
> between 7% and 28% of hospitalized have acute myocardial injury So, for a younger (< 60) otherwise healthy person whose chance of death with covid is less than 1%, it would seem ill advised to take this medication at the onset of symptoms, unless the the disease itself causes similar or higher rates of heart damage.

w_t_payne 7y ago

Given that I need hydroxychloroquine to treat my rheumatoid arthritis, I'd like this hypothesis to be either proven or disproven as rapidly and as unambiguously as possible.

AlexandrB 7y ago
Because HCQ’s efficacy was briefly endorsed by a controversial political figure I fear that there’s no evidence in either direction will convince the true believers. This is now a political issue, like global warming. Hopefully someone is ramping up production so availability improves for those that actually need it.
- loopz 7y ago
  The science providing data is apolitical. It just takes its due time.
  - munk-a 7y ago
    Yup - and said controversial political figure jumped on the guess before the science was in and heavily endorsed it - this is likely leading to widespread misuse of a drug which is know to cause extreme damage to organs including kidneys, livers and eyes when misdosed and taken in excess.
  - AlexandrB 7y ago
    The science may be apolitical, but the choice to accept or reject the science can depend on your politics. I think the anti-vaccination movement has shown that no amount of evidence is sufficient if someone is strongly attached to a belief for ideological reasons.
    - loopz 7y ago
      That is why science is not leadership.
  - t-writescode 7y ago

bretpiatt 7y ago

Lots of conflicting research happening[1], until we get multiple controlled trials we won't really know. Here's one that shows improvements. [1] French ~50 patient study that tried Control, Hydroxychloroquine, and Hydroxychloroquine + Azithromycin combo: https://www.mediterranee-infection.com/hydroxychloroquine-and-azithromycin-as-a-treatment-of-covid-19/ https://www.mediterranee-infection.com/hydroxychloroquine-an...

war1025 7y ago
> Lots of conflicting research happening That's my main take-away at this point. I have seen enough reports saying it worked, and enough saying it didn't that I believe the answer is probably somewhere in the middle. My understanding is the best guess for how it works is by keeping the viral infection from becoming serious enough to require hospitalization. Similar to how proper treatment of wounds early on keeps them from getting to the gangrene stage where you need amputation. Unfortunately, politics. So the Left wants it to be completely no use at all, and the Right wants it to be a miracle drug. Most of the population really probably just wants effective treatments if they end up getting sick.
- the_af 7y ago
  I'm out of the loop here: why would any political faction not want an alleged cure to work? What's the goal here?
  - VBprogrammer 7y ago
    Trump all but prescribed it to the nation a miracle drug "a real chance to be one of the biggest game changers in the history of medicine". Questioning the wisdom of that, given how little we knew, is seen as a partisan attack on Trump.
  - winstonewert 7y ago
    Trump said positive things about it. The left wants Trump to be wrong about everything, so wants this it to fail. The right wants Trump to be right about everything, so wants it to work.

wyxuan 7y ago

This trial wasn't randomized, but a quasi randomized trial for HCQ whose preprint was leaked is here:https://www.dropbox.com/s/8b2govfsa6n0xbq/NEJM_Clinical%20Outcomes%20of%20Hydroxychlorquine%20in%20Patients%20with%20COVID19.pdf.pdf.pdf.pdf?dl=0 https://www.dropbox.com/s/8b2govfsa6n0xbq/NEJM_Clinical%20Ou... Study indicates that one adverse effect of HCQ (on top of not improving patient outcomes) is increased ventilator times.

onlyrealcuzzo 7y ago
From the paper: A total of 63 patients were included with 32 in the hydroxychloroquine arm. Hydroxychloroquine administration was associated with a need for escalation of respiratory support level compared to those that did not receive hydroxychloroquine at 5 days (p=0.013). The same findings were observed in a baseline-matched subgroup analysis. Absolute lymphocyte change in the hydroxychloroquine group was no different than supportive care alone (p=0.413). Hydroxychloroquine use trended towards worsening neutrophil-to-lymphocyte ratio compared to supportive care alone (+9.59 vs +1.58, p=0.51) as well as a higher risk for intubation (p=0.051).
- layoutIfNeeded 7y ago
  p=0.413 p=0.51 So, basically coin toss?
  - onlyrealcuzzo 7y ago
    You overlooked the major finding of the study: > Hydroxychloroquine administration was associated with a need for escalation of respiratory support level compared to those that did not receive hydroxychloroquine at 5 days (p=0.013). > p = 0.013
  - jeremysalwen 7y ago
    > was no different than supportive care alone (p=0.413). Yes, exactly, p=0.413 corresponds to a coin toss, or as the authors of the paper put it "no different". The p=0.51 figure seems to be a typo in the abstract. If you read the content of the paper, it says > The hydroxychloroquine group also had a strong but not statistically significant trend towards worsening NLR (p=0.051). So I believe they just accidentally moved the decimal place, and they are correctly avoiding calling the result statistically significant, but it is close.

th3829 7y ago

That's because it's not hydroxychloroquine that helps them. It's Zinc. It just allows for much better absorption of the Zinc. Same can be achieved by combining Quercetin and Zinc.

firasd 7y ago

When the Covid crisis is over, one of the strangest sub- plots will have been the fracas around Hydroxychloroquine. Starting from medical practitioners worldwide adopting its usage in a ‘cargo cult’ way, mimicking what other doctors were doing, to Raoult’s low- quality study. Then people in Silicon Valley (notably Elon Musk) picking up the idea. Followed by the explosion in the political sphere, from Trump pushing it at the White House podium, to Indian PM Modi reversing an HCQ export ban for Trump, to French PM Macron talking it up. All the while HCQ remained unproven for Covid use, while people trying it got hurt by cardiac side- effects (and one couple in a prominent incident mistakenly took different chemicals with a similar name), and patients with other conditions ran out of HCQ due to shortages. Maybe HCQ will be part of the standard of care for Covid- 19 in the future, but it’s seeming less and less likely. Meanwhile it’s definitely not a miracle cure, so the frenzied advocacy and adoption of this medicine will turn out to have been a bizarre story. (I wrote this up here https://twitter.com/firasd/status/1250125344469708801 https://twitter.com/firasd/status/1250125344469708801)

agumonkey 7y ago
The recent reports about low benefits of HCQ didn't stop Raoult from appearing in a video about the state of HCQ and covid-19 in his clinic. Sadly he seems to be yet again using very wide statistics to justify his views (covid is of no importance compared to yearly stats [0]) and digress into political attacks (his past interactions with pharma labs that weren't conflict of interests). I still can't say if he's a low hanging troll [1] or if he's just so far above the pack that everybody else is braining wrong. That's also his motto... he likes to discuss disruption and paradigm shift in his classes and talks about how every past paradigm was considered gold standard and only people breaking the mold advanced the state of the art. [0] unsurprisingly Musk is also very fond of wide stats to justify his AutoPilot ~feature [1] his lab specializes in repurposing well studied compounds for new diseases.. seems like leveraging past efforts to get success (if I go full paranoia :)
- _Wintermute 7y ago
  Even pre-covid, Raoult had a reputation for pumping out hundreds of really poor quality studies and making controversial public claims. It's a shame he's the one that's caught the attention of the general public, there's lots of good work going on with other potential treatments, but suddenly my social media is filled with armchair pharmacologists arguing about this one drug.

pcj-github 7y ago

Aside from these results, what is the proposed mechanism of benefit here? And why are we expecting a mechanism with hydroxychloroquine against this virus when essentially no small molecule therapies are effective against viruses in general?

mcguire 7y ago
Hydroxychloroquine is an immune suppressant and may help reduce the cytokine storm effect. How that interacts with the "you have to start it early" issue is unclear to me. And it might keep you from getting malaria while you have COVID19.
- thepangolino 7y ago
  The way HCQ is by accumulating in cells. It inhibits the replication of viruses by interfering with endosome/lysosome trafficking or viral protein maturation during virion maturation. (basically stops the virus from replicating)
  - chasd00 7y ago
    and, correct me if i'm wrong, zinc helps take it with a grain of salt but https://www.snopes.com/fact-check/zelenko-669-coronavirus-patients/ https://www.snopes.com/fact-check/zelenko-669-coronavirus-pa...
    - rq1 7y ago
      No grain of salt needed, the chloroquine is a zinc ionophore.
    - souprock 7y ago
      With the right grain of salt, you get zinc. Suggestions: zinc acetate, zinc chloride, zinc citrate
  - mcguire 7y ago
    "The way HCQ is by accumulating in cells." The original study that set off this flap ran for a period of 6 days. I don't know that 6 days is long enough for significant accumulation. Beyond that, unless someone has published something significant that I haven't seen, any hypothesis on the drug's effect on coronavirus is pure speculation.

drummer 7y ago

Instead high doses of vitamin C have proven to be very effective.

capnrefsmmat 7y ago

It's important to interpret these results carefully: "no evidence of efficacy" does not imply evidence of no efficacy, and in fact the uncertainty in this study is quite large. The sample size is small enough that it would be very hard for this study to detect the effect of hydroxychloroquine unless that effect is very, very large. From the abstract: > In the HCQ group, 2.8% of the patients died within 7 days vs 4.6% in the no-HCQ group (3 vs 4 events, RR 0.61, 95% CI 0.13-2.89), and 27.4% and 24.1%, respectively, developed acute respiratory distress syndrome within 7 days (24 vs 23 events, RR 1.14, 95% CI 0.65-2.00). The relative risks and confidence intervals are the important numbers here. For example, the relative risk for death is 0.61, meaning the observed risk of death was lower for patients treated with hydroxychloroquine -- but the confidence interval is 0.13 to 2.89, meaning the data is consistent with anything from the risk being much smaller to the risk being much larger. Since there were only 3 deaths in the treatment group and 4 deaths in the control group, it's very hard to draw precise conclusions about death rates. I think we can interpret this result to mean that hydroxychloroquine doesn't have a miraculously large effect, but the evidence is weak. Other commenters are correct that large randomized trials will be more definitive. (disclaimer: I am a statistician, not a doctor)

blakesterz 7y ago
Would it be the same thing to do 1,000 small studies like this one as doing one LARGE study with 1000x more people? Would the results be considered just as useful?
- lonelappde 7y ago
  Similar. That's called a "meta analysis" and tends to happen after many independent uncoordinated small studies have published.
  - emn13 7y ago
    Also, it's extremely hard to account for all kinds of biases and systematic errors in a meta-analysis. I'd take most meta-analyses, even by renowned statiticians, very, very skeptically. Teasing out small effects from samples that need corrections for lots of confounding factors, and then trying do combine many such results is next to impossible. If your effect is small enough that you need a meta-analysis in the first place, that's a warning sign. Some background: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0152719 https://journals.plos.org/plosone/article?id=10.1371/journal... (with perhaps more approachable explanation here https://www.talyarkoni.org/blog/2016/06/11/the-great-minds-journal-club-discusses-westfall-yarkoni-2016/ https://www.talyarkoni.org/blog/2016/06/11/the-great-minds-j... ) Obviously it's sometimes possible to do this right, but the reproducibiility crisis didn't appear out of nowhere; it's best to be wary of overly clever statistics; hard to know what you don't know.

jeffdavis 7y ago

Given the study's small sample size, it seems the only way it would have produced a conclusive result is if the effect size was huge (i.e. miracle cure). The study found some evidence of efficacy, but it was not significant given the sample size. A better headline would say something like: "study finds that HCQ is not a miracle cure for already-hospitalized covid-19 patients".

mcguire 7y ago
How much are you willing to pay for "not a miracle cure" on the basis of "eh, it can't hurt"?
- deleted 7y ago
  [deleted]
- jaywalk 7y ago
  Whether it works or not, HCQ is not a costly drug by any means.
- jeffdavis 7y ago
  Your point doesn't really make sense, because the purpose of a study like this is not for making treatment decisions; it's for making research decisions. I don't see anything in the study that discredits HCQ as a potential treatment, and therefore it makes sense to keep researching.
projektfu 7y ago
What effect size would be a “game changer”?
randcraw 7y ago
No. This study found no evidence of effectiveness as a treatment for COVID-19 in patients who need it. A sample size of 20 is sufficient to satisfy a .05 statistical significance threshold that hydrochloroquine had even the slightest positive effect. In this population, it did not. All therapeutic drugs are developed using in vitro and pre-clinical (non human animal) treatment groups no bigger than 20. When a well controlled and randomized study comparng two groups that are each four times larger than 20, we have a VERY strong indication that this drug delivers not only too little effect to be a useful treatment for COVID-19, but it very likely delivered absolutely NO EFFECT AT ALL in hospitalized patients. Don't expect any reputable physician or scientist to dismiss this evidence. This is very bad news for the prospect for treating patients who need it using this drug -- those people who are likeliest to die or endure lasting harm. The other 80% of positive patients don't need any therapy except time.

mfer 7y ago

It's important to note that this study did not evaluate or note that Hydroxychloroquine had no effect on all people in all situations with COVID-19. This was a targeted study looking at a specific circumstance. The situation was "all adults in 4 French hospitals with documented SARS-CoV-2 pneumonia and requiring oxygen ≥ 2 L/min" So, adults who were not on oxygen are not included in the study. How does it pertain to them? That's not covered by this. It reads like it's saying people who are in bad shape and on ventilators did not have a positive impact by Hydroxychloroquine. This still leaves open questions like, can the use of Hydroxychloroquine lower the rate of needing to get on a ventilator. I look forward to someone reproducing this study and looking into the other areas.

deleted 7y ago

[deleted]

edoo 7y ago

What a joke. An emulated trial only in patients already requiring oxygen. How about this http://covexit.com/professor-didier-raoult-releases-the-results-of-a-new-hydroxychloroquine-treatment-study-on-1061-patients/ http://covexit.com/professor-didier-raoult-releases-the-resu... I'm taking the HQZ cocktail at first diagnosis even if I have to doctor shop.

sheinsheish 7y ago

I don’t understand who gets to decide and how, which of these people receive / don’t receive a specific treatment. I’ve always loved medical studies, but now the crisis got me to thinking about the moral decision (playing god?)

CydeWeys 7y ago
The answer is, by and large, doctors. Within the hospitals they really do have the power of life and death, deciding who gets treatment when supplies are thin. Generally the decisions are made using the heuristic of "With this limited stock of X, who should we give it to to save the maximum possible number and quality of lives?" It's not playing god, it's just making rational decisions in times of scarcity. That's something humans do constantly, no god necessary.
DanBC 7y ago
You might be interested in this letter from the BMA: https://www.bma.org.uk/media/2283/bma-ethics-guidance-and-age-and-disability-statement-april-2020.pdf https://www.bma.org.uk/media/2283/bma-ethics-guidance-and-ag... > This note addresses in more detail the relationship between our guidance and those patients who are elderly or who have disabilities. It emphasises that neither age nor disability are in themselves relevant criteria for making decisions about treatment. This follows on from widespread (and perhaps misleading) reporting about a tool. This tool has NHS branding, but it doesn't appear to have come from NHS_England+Improvement. http://prod-upp-image-read.ft.com/765d3430-7a57-11ea-af44-daa3def9ae03 http://prod-upp-image-read.ft.com/765d3430-7a57-11ea-af44-da...

bcrosby95 7y ago

And to put this interpretation into perspective, people that need this drug for diseases that it has proven to have a large effect on are losing access to it because it may or may not help with COVID-19.

beaner 7y ago
Is there a source for this claim?
- DangerousPie 7y ago
  There were lots of newspaper articles a few weeks ago about lupus patients struggling to access HCQ. Eg: https://www.nytimes.com/2020/04/06/opinion/coronavirus-hydroxychloroquine-lupus.html https://www.nytimes.com/2020/04/06/opinion/coronavirus-hydro... or https://www.washingtonpost.com/politics/2020/04/13/how-false-hope-spread-about-hydroxychloroquine-its-consequences/ https://www.washingtonpost.com/politics/2020/04/13/how-false...
- eesmith 7y ago
  Wikipedia links to two WaPo articles at https://en.wikipedia.org/wiki/Hydroxychloroquine#Regulatory_approval https://en.wikipedia.org/wiki/Hydroxychloroquine#Regulatory_... Guardian article - https://www.theguardian.com/world/2020/mar/27/vital-drug-people-lupus-coronavirus-covid-19-link-hydroxychloroquine https://www.theguardian.com/world/2020/mar/27/vital-drug-peo... . It cites someone from Lupus UK. Their page at http://www.lupusuk.org.uk/uk-azathioprine-supply/ http://www.lupusuk.org.uk/uk-azathioprine-supply/ says "we have received reports from a number of people with lupus who have been unable to fulfil their prescription of azathioprine" and that "stocks are in the process of being replenished and should be available in the UK in mid-April". Comment from an HN'er: "For several weeks my mother hasn't been able to fill her regular prescription for hydroxychloroquine that has been an important part of managing her lupus for >30 years." - https://news.ycombinator.com/item?id=22793293 https://news.ycombinator.com/item?id=22793293
  - beaner 7y ago
    Is this shortage universal? Have there been shortages before, either universal or local? Is there evidence that this particular local shortage is due specifically to coronavirus demand? It may be that the answer to these questions is "yes," but that answer seems to be being assumed right now.

williesleg 7y ago

Hey, if you don't want to take it, don't. Simple as that.

pdonis 7y ago

A useful compilation of information on HCQ and COVID-19: https://docs.google.com/document/d/1O6Cls-Oz2ZAgJuyDbnICEGjMvQPEyM-aaXARUomR9Ww/edit https://docs.google.com/document/d/1O6Cls-Oz2ZAgJuyDbnICEGjM...

DevKoala 7y ago

The sample was 185 patients. There are anecdotal evidences that support the medicine which claim to have more, the letter came from a French doctor too. The study is discouraging for sure though.

twomoretime 7y ago

It really bothers me how hard both citizens and officials seem to be wanting Chloroquine to fail all because somebody they didn't like endorsed it publicly. Can't let him have that win, right? Like children. The original studies that showed promise used combinations of Chloroquine, Azithromycin, and or zinc, and there is a speculated pathway by which these drugs interact to interfere with COVID replication. This study only looked at HCQ. This kind of partisan, childlike pettiness is dangerous to all of us - what if Chloroquine works but we overlooked it because a couple shitty papers told us what we wanted to hear? Was it appropriate to tweet about? Debatable. It is a presidents job to keep his people hopeful when possible, and this drug cocktail was in multiple (admittedly not perfect) papers at the time of the tweet. People need to be more objective when evaluating statements made by the president. That doesn't mean you have to like him.

nkozyra 7y ago
I think there's a bunch of strawmen here. It's disingenuous to say that people who found [said person]'s comments to be a bad idea want it to fail. Indeed, if that person had come up and said "there's a lot of promising treatments, such as ..." or "the experts are telling us that some studies involving [x, y, z] are showing some positive signs" or something of that ilk, nobody would have cared. Instead, the person multiple times touted something that is to date unproved. People find that irresponsible for a number of reasons, not least of which that there are legitimate users who need this and it's now in short supply. So what people are protesting is someone not waiting for medical science and just causing noise. Like many things, this person could have handled this all more responsibly.
- twomoretime 7y ago
  >https://youtu.be/oWQjWepaDv0 https://youtu.be/oWQjWepaDv0 "Very promising early results". >https://www.google.com/search?q=trump+tweet+chloroquine&prmd=insv&source=lnms&tbm=isch&sa=X&ved=2ahUKEwjvzOjehOvoAhVICc0KHcxyD8gQ_AUoAXoECAwQAQ&biw=412&bih=556&dpr=2.63#imgrc=sU_DAlax8JfVaM https://www.google.com/search?q=trump+tweet+chloroquine&prmd... "Have a real chance to be one of the biggest game changers" Meanwhile the media response has been universally lamenting that a president would "tell people" [he didn't] to take this drug. How many outlets jumped on the single chloroquine phosphate overdose as proof of the president's responsibility? I encourage you to search "Trump" and "chloroquine" and find me a single headline that doesn't tear into Trump. Like most people, your views have been warped by headlines and op-eds being touted as "news." The fact that the president acts like a child doesn't mean our news should too. The petty editorialization of the daily briefings are an excellent example - the media's job in such a case is to be an objective first source - not to force their point of view through adversarial headlines that change every 5 seconds and "fact checking" only his alleged untruths. But this is where the majority of Americans get their news. It's shameful. Edit: hell, look at this absolutely ridiculous headline at the top of the CNN "fact check" page: "Fact check: Trump denies saying another thing he said and makes more false claims at coronavirus briefing" What kind of headline is that? Is anyone competent left at CNN? The media no longer deserves the soft power it wields. They lost that privilege when they strayed so far from any semblance of objectivity.

hartator 7y ago

> documented SARS-CoV-2 pneumonia and requiring oxygen ≥ 2 L/min to emulate a target trial aimed at assessing the effectiveness of HCQ at 600 mg/day Well hydroxychoroquine is only useful before ventilators are needed (it attacks the full lungs) and is actually detrimental - we know that - after by its nature. What kind of bad science is this study where you actually push patients through a known dangerous path to try to prove the non efficiency of a potential treatment.

ejstronge 7y ago
>Well hydroxychoroquine is only useful before ventilators are needed (it attacks the full lungs) and is actually detrimental - we know that - after by its nature. I’m worried that this has totally left the realm of science and is just pure politics... there is no evidence for a ‘magic window’ for HCQ in COVID-19 treatment, or any solid evidence of a positive role. Secondly, having supplemental oxygen is not the same as being on a ventilator. I imagine most hospitalized COVID patients need oxygen (otherwise, they could be managed at home). I hope we all avoid making comments (or even accepting comments) about medicine without either critical, independent study or background knowledge.

mcguire 7y ago

While we're here, "Traditional Chinese Medicine in the Treatment of Patients Infected with 2019-New Coronavirus (SARS-CoV-2): A Review and Perspective" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7098036/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7098036/) Hey, it can't hurt and it might help. China has had one of the best recoveries from the pandemic.

forgingahead 7y ago
Thanks for sharing this, not sure why you're getting downvoted. TCM has its place, Artemisia Annua has been used as an anti-malarial treatment as well for hundreds of years, and again, is cheap, available, and side effects are known. I've had anecdotal experience that it's helpful for milder coronavirus symptoms.
- AlexandrB 7y ago
  > Thanks for sharing this, not sure why you're getting downvoted. Because TCM is - charitably - pseudoscience. Many of its remedies involve grinding up endangered animals into concoctions that have no plausible mechanism of treating the thing they're meant to treat. > I've had anecdotal experience that it's helpful for milder coronavirus symptoms. I have anecdotal experience that my microsorium musifolium plant has been effective in preventing coronavirus infection in my household. Unfortunately, just like your statement, this doesn't qualify as evidence and shouldn't be used to make public health decisions.
  - forgingahead 7y ago
    You are mindreading my comment of "TCM has its place" and are wrongly confusing it in your own imagination of "used to make public health decisions". Please don't do that, it's insulting to folks trying to have open discussions, and it also makes you, the mindreader, stressed and anxious about things that are not happening.
perardi 7y ago
I cannot tell if you are purposefully trolling, or this is sincere. Regardless, let's wade in… 1. That's not's a study. That's not a metareview. That's a puff piece by people who have a strong, strong self-interest in promoting TCM, because they want to keep their department chairs. 2. Oh heck, I'll just quote the entire last paragraph: "The safety of TCM in the treatment of emerging coronavirus diseases was not included in the observation on SARS patients. It was reported that some herbs used in TCM contain nephrotoxins and mutagens, while the toxicological features of the most of Chinese herbal medicines remain to be fully understood. Furthermore, herbs used in TCM can mimic, or magnify, or oppose the effect of conventional medicines. Thus, the safety of TCM used in treatment of emerging coronavirus infections should be carefully evaluated. It is particularly important to avoid toxicity or interfere with the efficacy of conventional treatment caused by herb-drug interaction." So, in conclusion, we don't know if this works, and this stuff may be toxic, and it may have drug interactions, and oh by the way there's no quality control on this so you have no idea what's in the medications. Might as well recommend acupuncture and getting your chakras aligned, couldn't hurt! (Probably less of a chance it hurting than taking a wild dose of unregulated herbal supplements.)

forgingahead 7y ago

This whole debate is insane to me -- some people that so-called "experts" don't like mentioned HCQ as a possible treatment for coronavirus, and we've ended up in some bizarro world where everyone is shouting and fingers are being pointed over something that really shouldn't be controversial or perceived as some sinister plot to destroy clever society. 1. HCQ has been used for many decades 2. The side effects are generally known 3. It may have a positive impact on COVID-19, and it may not. 4. Nobody is suggesting long term high doses for anyone, COVID patients or otherwise. 5. If people are severe patients of COVID-19, this should certainly be tried as a treatment as long as the patient (or immediate family) is briefed on the potential side effects. The alternative, potential death, makes this a worthy discussion for a doctor/patient to have, with families being allowed to err on the side of right-to-try. HCQ is cheap, available, and has been used for decades. The fact that "no evidence HCQ works!!" has 200 points of upvotes and counting when the sample size for this study is 181 patients only just shows how high the temperature has become. Everyone just calm down. As capnrefsmmat has eloquently pointed out, "absence of evidence" does not mean "evidence of absence". If you enjoy the thrill of debates for debates sake, here are other potential topics for you: Whether masks are effective, condoms, seatbelts, helmets, or even parachutes[0]: [0]https://www.ncbi.nlm.nih.gov/pmc/articles/PMC300808/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC300808/ Favourite part: Results We were unable to identify any randomised controlled trials of parachute intervention. Conclusions As with many interventions intended to prevent ill health, the effectiveness of parachutes has not been subjected to rigorous evaluation by using randomised controlled trials. Advocates of evidence based medicine have criticised the adoption of interventions evaluated by using only observational data. We think that everyone might benefit if the most radical protagonists of evidence based medicine organised and participated in a double blind, randomised, placebo controlled, crossover trial of the parachute.

DangerousPie 7y ago
1. Not for coronaviruses. 2. They are known but they are by no means mild. A trial in Brazil just got aborted due to severe heart problems. 3. So does almost everything. If that's your threshold for taking a drug then I have a lot of homeopathic remedies to sell you! 4. Actually the doses given for COVID are often higher. Not sure what long-term has to do with anything. 5. That assumes that the risk of side effects is zero. It's not. Also, there is an opportunity cost to taking HCQ instead of something else. I totally agree with you that we should do proper trials on this and see what happens. But right now there is zero evidence that it actually works, and some (admittedly low-quality) evidence that it might not.

jonplackett 7y ago

Why is it taking so long to do a big study on this? There are so many sick people and it’s a cheap drug and only takes a week Or 2 to see if it works. Can someone please just do a Really large trial, like, 2 weeks ago so we can put this to bed one way or the other.

stevespang 7y ago

Very possible that once a patient has deteriorated to needing hospitalization with O2, it may be too late for hydroxychloroquine to be of benefit - - the virus has already destroyed the lungs.

m0zg 7y ago

Wow, several HCQ stories on the front page. Means it's probably going to be proven effective soon.

Techies4Trump 7y ago

Sample size is far too small. If anything this study shows (albeit with small numbers) that HCQ doesn't make things worse. But I have a feeling HCQ will be found to be effective. Big pharma have a lot of $$$ to make from their vaccine though.

Khelavaster 7y ago

This study is basically garbage. It applies to people who're so damaged from Covid they need at least 2 liters of oxygen per minute. It studies treatment with pure hydroxychloroquine--no zinc, no azithromycin/doxycycline/ivermectin. Hydroxychloroquine. Patients who get their treatment from doctors less fraudulent than the authors of this study almost certainly see better outcomes.

tgafpc2 7y ago

"collected data to emulate a target trial" I take it this means it's not an actual clinical trial, just a virtual trial? What's the point? Of all the people that died, none were saved by the drug. Sounds like an insurance ad.

DoreenMichele 7y ago

This study is specifically about patients sick enough to be put on oxygen. The top ranked comments don't seem to address that detail. Some thoughts: My understanding is this is a powerful alkaloid. My experience has been that similar compounds can help combat inflammation. They also can work to help kill infection at times. By the time people with Covid19 need oxygen, inflammation doesn't seem to be the primary problem. So I wouldn't think it would be particularly helpful at that point. Ventilators get prescribed in part on the assumption that inflammation in the lungs is a major impediment to getting sufficient oxygen. Ventilators are failing at a shockingly high rate, with a death rate up around 80% or so. Some doctors are moving away from ventilators because the death rate is so high. I spoke recently with a researcher who suggested impaired vasodilation was a possible explanation for the reports of low oxygen combined with a surprising lack of pneumonia and inflammation in some cases and that makes a lot of sense to me. The mechanism causing low oxygen does not appear to be the obvious answer of "lung inflammation and pneumonia." That doesn't mean this drug can't play a meaningful role at some stage. It mostly means it's not the magic bullet solution for advanced cases that they were hoping for. This in no way surprises me because the things it actually treats do not appear to be the cause of low oxygen in advanced covid19 cases.

firasd 7y ago
You might find this thread interesting (“There's a growing body of data to strongly suggest #COVID19 predisposes to both venous and arterial thromboembolism due to excessive inflammation, hypoxia, immobilization and diffuse intravascular coagulation.”) https://twitter.com/scottgottliebmd/status/1250069609581031428?s=21 https://twitter.com/scottgottliebmd/status/12500696095810314...
- DoreenMichele 7y ago
  Thank you. It is interesting stuff and fits with some of my impression that they are overlooking important blood-related issues. Anemia (a blood disorder) is also a cause of low oxygen. That's not exclusive to lung function. Glad to see some doctors are working on that angle. (crosses fingers, hopes for better treatments soon)

thanatropism 7y ago

There are dozens upon dozens of speculative treatments. Interactome research is churning out candidates. I think the people have a right to know about cloroquine, since it became such a political point. But n=181 is not that small.

mekoka 7y ago

I think it's too bad that this drug has been so politicized. It's really unfortunate that its two original and most prominent champions are people that are so disliked. So many people spoke up (maybe prematurely) against it in a knee-jerk reaction to its advocates. Now many act as if they're more concerned about being right to ridicule the claims all along, than they are about whether the drug is actually helpful in fighting COVID-19. Which, for the rest of us without a stake in their stupid political feuds, is all that matters. And because of this idiotic battle of the egos we could be passing on something useful. So here we all are, hanging by the edge of our seats, waiting for definitive proof that HCQ does not help in fighting COVID-19 and we keep getting these half-assed reports, seemingly more aimed at pushing a narrative than to present (or eliminate) an option in a fight. One of the latest examples is the account of Rita Wilson (wife of Tom Hanks) who survived what seems like a difficult case of COVID-19 and shared her experience with the media: she felt very tired, extremely achy, uncomfortable, didn't want to be touched, on the ninth day her fever climbed up to 102 and she had chills like she'd "never had before" (her words), she lost her sense of taste and smell. Then she was given chloroquine, her fever broke (it's not clear how long after). She goes on to warn against the "extreme" (her word) side-effects she attributes to chloroquine: she was completely nauseous, she had vertigo, she could not walk and her muscles felt very weak. She then concludes that although her fever broke after been given chloroquine, she doesn't know if it helped or if it was just time, which is fair. What do you imagine the headline for that story should be? Well, to save you the trouble, most read like this Rita Wilson warns against "extreme" side-effects of chloroquine. Are HCQ/CQ effective? We're still sitting here like idiots not knowing. If they are, should they be taken carelessly? Definitely not, we already got that, thanks, but that is not the point. We can't afford to have an "all or nothing" mindset with these drugs as we did with masks. Simply proclaiming that HCQ is useless because it is shown not to reduce viral load is just the best way to pass on some other ways it might be helping. If it is shown to have other palliative effects that actually help patients in their fight, such as reducing inflammation or helping cope with high fever long enough for your immune system to do the job, it's not nothing. It's information. It's an option.

krn320 7y ago

There is an obvious pushback on hydroxychloroquine. Not enough money to be made so other "solutions" are preferred. Something that was used for more than 50 years is being tested for safety? What a joke. I'm sure when vaccines arrive they'll be "safe and effective" and used all around the world from day one...

krn320 7y ago

There is an obvious pushback for hydroxychloroquine. Something that was used for more than 50 years should've been widely adopted by now but there is not enough money to be made (and let's not forget political issues). I'm sure when vaccine arrives it'll be "safe and effective" and widely used around the world from day one - no questions asked.

cameldrv 7y ago

The study is way underpowered (too small a sample). Based on the raw numbers, the HCQ group had less deaths and less ICU admissions, but the numbers we're talking about are 3 vs. 4 deaths and 16 vs. 21 ICU admissions (group sizes were different). These numbers simply aren't enough to make a determination one way or the other. On mortality, the 95% confidence interval allows for a range of HCQ reducing death rates by 87% up to it increasing death rates by 2.9x.

droithomme 7y ago

Hm, the pseudo-study (it was a after the fact data review) found a near halving of mortality rates in the HCQ group. Yet that is described as no evidence of efficacy. Odd.

dfsajlkjadfalk 7y ago

Open America Now!

projektfu 7y ago

I know this study doesn’t put anything to bed, but one has to understand that the basis for the HCQ and CQ (+/- zinc) thing is the same as x kills cancer in vitro. Then, you get a motivated researcher who publishes a single arm study of essentially OK patients claiming zero deaths. Game changer? We’ll see. But I imagine there are hospitals that are already using this as a first line treatment and there’s no positive reviews from the front line. Beyond that, we do have the ability to perform small sample studies (cf. Student) and decide whether we’re headed in the right direction. Are we in a lull in statistics where we can’t even use statistics to guide future research?

maa5444 7y ago

italian doctor proposed a working cure .... his name is molinari

giardini 7y ago

full title "No evidence of clinical efficacy of hydroxychloroquine in patients hospitalised for COVID-19 infection and requiring oxygen:..." from the article: "We used data collected from routine care of all adults in 4 French hospitals with documented SARS-CoV-2 pneumonia and requiring oxygen ≥ 2 L/min to emulate a target trial aimed at assessing the effectiveness of HCQ at 600 mg/day... This study included 181 patients with SARS-CoV-2 pneumonia; 84 received HCQ within 48 hours of admission (HCQ group) and 97 did not (no-HCQ group). The median age of patients was 60 years ..." "...[Patients were from] four French tertiary care centres providing care to patients with COVID-19 pneumonia. Adult patients were eligible in this study if they were aged between 18 years and 80 years, had PCR-confirmed SARS-CoV-2 infection, and required oxygen by mask or nasal prongs (corresponding to a WHO progression score of 5)." "Among the 181 patients eligible for analysis, 84 received HCQ within 48 hours of admission and 97 did not (although 8 of them did receive HCQ later on)." So, first of all, these patients were infected with Covid-19 _days_ prior and now had progressed to pneumonia. The up to two-day delay in the administration of HCQ after admittance to the study is disheartening. I am surprised that, despite the experimentors selecting an elderly, pneumonic, oxygen-dependent cohort in advanced stages of the disease, these patients did as well as they did. Its a credit to the human body. But timing is everything... Once a Covid-19 patient has developed pneumonia, it is too late for hydroxychloroquine to affect the Covid-19 virus' replication process significantly. The patient's body is saturated with the virus. In a patient who has developed pneumonia the disease has progressed to a second phase wherein the virus and other opportunistic pathogens (e.g., bacteria) attack the lungs and other tissue. Antibiotics may help at this point. But it is quite clear that the patients in this study arrived too late to gain any benefit from hydroxychloroquine which, when coupled with zinc sulfate, slows or halts viral replication _early_ in the disease, delays or halts the virus' progress and allows the body time to develop an immunological response to the virus. The study's conclusion states explicitly that " These results ... do not support the use of HCQ in patients hospitalised for a documented SARS-CoV-2 pneumonia." So, the trick is to treat _early_ with HCQ+zinc sulfate+azithromycin.

newintellectual 7y ago

They apparently omitted a critical component: zinc.

cheese4242 7y ago

400+ points on Hackernews for... this? There have been a variety of studies and reports, both for and against, the use of hydroxychloroquine. Is there any reason this particular study is so highly upvoted? Or is this just an attempt to dunk on Trump for suggesting the drug showed promise?

tigershark 7y ago
It’s a study with a fairly high number of participants and it has not been conducted by the controversial author of the flawed first study.