8 ms·

First hydroxychloroquine randomized controlled trial: results disappointing

199 points by aaavl2821 7y ago

aaavl2821 7y ago
didnt find a link to the abstract, seems the results are just being published link to the trial on clinicaltrials.gov is here: https://clinicaltrials.gov/ct2/show/NCT04261517 https://clinicaltrials.gov/ct2/show/NCT04261517 patients in both tx and control arm fared better than in the french study from earlier this week, suggesting patients were healthier / lower risk at baseline patients got slightly lower dose in this study (400 mg / day) vs the french study (600 mg / day)
- hartator 7y ago
  Kind of crazy these are not in the open. Especially when we are used to work in software.
  - aaavl2821 7y ago
    It may be that they just presented an abstract and the manuscript has not yet been submitted for publication or peer reviewed
    - hartator 7y ago
      Well let's peer review this wikipedia-style. Not sure why academia is stuck in last century.
      - aaavl2821 7y ago
        scientists have increasingly been doing this during covid by publishing on biorxiv and then discussing on other channels (twitter etc) for ex, this paper [0] by UCSF analyzing 26 of the 29 viral proteins expressed by the virus was posted on biorxiv and publicized further via twitter [1]. they identified 69 FDA approved drugs that target these proteins, giving the medical and scientific community a massive head start on studying drugs that could potentially be near-term treatments there are some parts of academic science that are stuck in the last century but scientists themselves are certainly not for those interested in learning more about how science works and how scientists operate, the covid situation is a great way to see how its done. modern science is amazing [0] https://www.biorxiv.org/content/10.1101/2020.03.22.002386v1 https://www.biorxiv.org/content/10.1101/2020.03.22.002386v1 [1] https://twitter.com/kevansf/status/1241936588164063233 https://twitter.com/kevansf/status/1241936588164063233
        raphlinus 7y ago
        Yeah, I'm following a bunch of scientists on Twitter and have been watching from the sidelines with awe and admiration. The contrast to the seeming hordes of dumbfucks could hardly be more remarkable; sometimes it's hard to keep in mind the same platform is host to both sets of people.
        godzulu 7y ago
        This Doctor in NY seems to have had great results so far https://www.thegatewaypundit.com/2020/03/stunning-ny-doctor-vladimir-zelenko-finds-100-success-rate-in-350-patients-using-hydroxychloroquine-with-z-paks-video/ https://www.thegatewaypundit.com/2020/03/stunning-ny-doctor-... This Doctor, Health Commissioner of NYC, Oxiris Barbot, seemed to take a lot of joy in proclaiming: Today our city is celebrating the #LunarNewYear parade in Chinatown, a beautiful cultural tradition with a rich history in our city. I want to remind everyone to enjoy the parade and not change any plans due to misinformation spreading about #coronavirus. https://on.nyc.gov/377LlcH https://on.nyc.gov/377LlcH https://t.co/bwCnIb7j8H https://t.co/bwCnIb7j8H Which Dr deserves awe and admiration and which brings with the seeming hordes of dumbfucks? https://www.amny.com/editorial/city-leaders-seek-to-allay-fears-of-coronavirus-in-chinatown/ https://www.amny.com/editorial/city-leaders-seek-to-allay-fe...
        arcticbull 7y ago
        > This Doctor in NY seems to have had great results so far https://www.thegatewaypundit.com/2020/03/stunning-ny-doctor-.. https://www.thegatewaypundit.com/2020/03/stunning-ny-doctor-.... Let's stick with legitimate news sources. Either way no data is provided there, but the case fatality rate for folks under 10 is 0% and under 29 is between 0.1% and 0%. If this hypothetical doctor even exists, it wouldn't be hard to pick 350 people, give them some HCQ and Azithromycin and have 100% of them recover -- as they would have even if they hadn't received anything. That's more or less what this study shows. In fact, as the fatality rate for under-29s is 0.1%, you have a 70% ((1-0.001)^12) chance that any randomly selected 350 of them will recover.
        raphlinus 7y ago
      - im3w1l 7y ago
        Wikipedia style is unreliable. I'm aware of quite a few errors. Why I don't fix them then? Because my edits would be reverted. Or because the page has been locked. Academic literature in contrast, has multiple parallel journals. If one is suppressing you, you can go to the next. Of course if you go to a less reliable one, then people might not trust your research.
- raphlinus 7y ago
  Someone on the Twitter thread linked to this, which seems to be not exactly the same document but contains very similar text in the abstract: http://subject.med.wanfangdata.com.cn/UpLoad/Files/202003/43f8625d4dc74e42bbcf24795de1c77c.pdf http://subject.med.wanfangdata.com.cn/UpLoad/Files/202003/43... I think it helps if you can read Chinese, though Google Translate seems to do a pretty ok job on it.
  - HarryHirsch 7y ago
    No need to read Chinese, the abstract is on page 2. Conclusion: at current trial size no better than placebo. More study is needed to tease out an effect, if there is any.
    - rurban 7y ago
      It does help if you read the translation. By now everybody should know that the successful dosis is 2x500mg per day for 10 days. Not 1x 400mg per day, which is the old dosis for Malaria prevention. This dosis needs at least 2-3 weeks to be effective (saturate the cell membranes with zinc), and by then the infection is already over. And the Chinese treatment plan contained much more. A study with zero value.
      - newsbinator 7y ago
        What's the source of this?
        rurban 7y ago
        The official chinese treatment recommendation. https://old.reddit.com/r/COVID19/comments/fd28s6/preprint_article_from_the_shanghai_medical/ https://old.reddit.com/r/COVID19/comments/fd28s6/preprint_ar... Amongst doctors both hydroxychloroquine sulfate and chloroquine phosphate run under broadband antiviral.
JohnJamesRambo 7y ago
> That was a first run trial without the Zpak. The following trial with both showed 100% efficacy after 5-6 days. Is that twitter reply accurate?
- sfteus 7y ago
  No, that trial has some glaring flaws. Several threads go into them way better than I could. https://twitter.com/GaetanBurgio/status/1241201751916568576 https://twitter.com/GaetanBurgio/status/1241201751916568576 https://twitter.com/MicrobiomDigest/status/1241429544847863808 https://twitter.com/MicrobiomDigest/status/12414295448478638...
  - JohnJamesRambo 7y ago
    Thank you for the links! I didn’t know about those gremlins in the supplementary info. Hopefully the WHO trials recently announced will give us a better answer soon.
- Khelavaster 7y ago
  Both trials have glaring flaws: they're tiny.
  - sfkdjf9j3j 7y ago
    What's wrong with the size of the 30 patient experiment?
    - cycrutchfield 7y ago
      The French study? Aside from the fact that it wasn't a randomized study and 6 patients dropped out from the treatment group (1 died, 3 went to ICU)?
    - sfteus 7y ago
      30 patients would be statistically significant. Problem is that they were non randomized, open-label, and they seemingly discarded some of the bad results. They also measured viral load, not cure, and the measurement was not done correctly in all cases. It's basically a "there could potentially be a causal link here; needs way more research" type of study.
HarryHirsch 7y ago
Not unexpected. A week or two ago a Chinese treatment protocol made the rounds where hydroxychloroquine was suggested as an alternative to HIV protease inhibitors. Since we now know that ritonavir/lopinavir doesn't work well, one wouldn't expect hydroxychloroquine to do any better. If it had remarkable clinical effects it would be the first-line treatment.
akarve 7y ago
The reported dosage is less than half what the Chinese Government recommends (500mg x 2 (BID)). So it's possible that they didn't hit the effective dose. https://medium.com/@balajis/the-official-chinese-government-guide-to-diagnosing-and-treating-the-novel-coronavirus-9d06868f8df4 https://medium.com/@balajis/the-official-chinese-government-...
- hcknwscommenter 7y ago
  your link is to chloroquine phosphate, which has a phosphate group and is only like 75% chloroquine by weight. So no, not less than half. Moreover, you are trying to compare a hydroxychloroquine dose with a chloroquine phosphate dose (active ingredient is chloroquine, not hydroxychloroquine), which is any one's guess if they even have the same mechanism of action here. Just because they both work against malaria, doesn't mean much about this virus. All in all, it is nearly useless to compare the chloroquine phosphate dose and outcomes to the hydroxychloroquine dose and outcomes.
  - tzjmetron 7y ago
    Pertinent.
mirimir 7y ago
Wait. I thought that hydroxychloroquine was hypothesized to protect against wet lung, as an anti-inflammatory, and not as an antiviral. Did I just make that up?
- rurban 7y ago
  No, HCQ is the Antiviral. Anti-inflammatories are also in the plan, but not Iboprofen.
  - arcticbull 7y ago
    Not exactly. HCQ has anti-inflammatory action as well as immune moderating action [1] the latter of which may help protect against cytokine storm which occurs in some serious COVID-19 infections. It also has antiviral action in some situations but it's not clear that that's actually relevant to COVID-19 yet. [1] https://en.wikipedia.org/wiki/Hydroxychloroquine https://en.wikipedia.org/wiki/Hydroxychloroquine
    - mirimir 7y ago
      Thanks. Upon reflecting, I meant to say immune moderating as well as anti-inflammatory. Which is why it's become so popular for treating arthritis. I wonder about the antiviral activity, though. What I've read is about possibly faster drop in virus levels. And I suppose that HCQ could be interfering with some stage of intracellular virus production. But time will tell.
      - rurban 7y ago
        You're mixing it up: CQ Phosphat is the rheuma/arthritis treatment, HCQ Sulfat the malaria prevention drug. CQ has much more severe side-effects, esp. in blacks. HCQ can lead to temporal blindness after years of use. We are talking 10 days here.
nikolay 7y ago
I am sorry, but isn't the mechanism of action that hydroxychloroquine is simply a zinc ionophore, i.e. you need enough free zinc in the blood for this to work? I read doctors suggesting using hydroxychloroquine along with 50mg of ionic zinc.
- Reelin 7y ago
  CQ (and HCQ, etc) have multiple potential mechanisms of action. I don't believe we know how it works in this particular case yet, or if it even works at all. It is indeed a zinc ionophore, [1] and those are known to impair the replication of a number of RNA viruses. [2] However, there are a number of other mechanisms at play here as well. [3] > Both CQ and HCQ are weak bases that are known to elevate the pH of acidic intracellular organelles, such as endosomes/lysosomes, essential for membrane fusion5. In addition, CQ could inhibit SARS-CoV entry through changing the glycosylation of ACE2 receptor and spike protein6. Time-of-addition experiment confirmed that HCQ effectively inhibited the entry step, as well as the post-entry stages of SARS-CoV-2, which was also found upon CQ treatment (Supplementary Fig. S2). [1] https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0109180 https://journals.plos.org/plosone/article?id=10.1371/journal... [2] https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1001176 https://journals.plos.org/plospathogens/article?id=10.1371/j... [3] https://www.nature.com/articles/s41421-020-0156-0 https://www.nature.com/articles/s41421-020-0156-0
- omgwtfbyobbq 7y ago
  Like Reelin said, it's effectiveness may be related to it's ability to modulate immune activity by affecting pH. https://www.ncbi.nlm.nih.gov/pubmed/27927040 https://www.ncbi.nlm.nih.gov/pubmed/27927040 Course, that'll only work if the symptoms are being caused by an overactive immune system and it's able to mediate that immune response in time.
  - deleted 7y ago
    [deleted]
  - arcticbull 7y ago
    > Course, that'll only work if the symptoms are being caused by an overactive immune system and it's able to mediate that immune response in time. Accumulating evidence suggests that a subgroup of patients with severe COVID-19 might have a cytokine storm syndrome [1]. HCQ is known to moderate this reaction. [1] https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30628-0/fulltext https://www.thelancet.com/journals/lancet/article/PIIS0140-6...
djvu9 7y ago
It is a 30 patients test and almost everybody’s fever was gone right after enrollment. Even the swab test results turned negative in 2-4 days. Why is medicine ever needed for such group of patients?
- jansan 7y ago
  The results are disappointing because they are useless. That's how I interpret the headline.
throwaway5466 7y ago
For people that didn't read: it's "disappointing" because both the control and study groups largely tested negative (93% and 87% respectively). That 87% figure sounds worse than the control but it actually is better than in the French study. What happened in essence is that almost all cases were mild so the patients almost all got better after a while, with or without medication. This doesn't mean HCQ is ineffective, only that its efficacy couldn't be measured in this instance. And I wouldn't call a study where almost everyone gets better at the end "disappointing".
- deleted 7y ago
  [deleted]
- cycrutchfield 7y ago
  It's disappointing because it's no better than placebo.
  - arcticbull 7y ago
    In this case (as with many others) placebo is pretty effective, but also, these folks didn't get sick enough to need it, as with the overwhelming majority of young and healthy people. Another, broader study is required. I'm sure we'll find out more soon -- this reads like a mulligan though.
    - dajohnson89 7y ago
      any data on what percentage of “young healthy” people die/get hospitalized? also, what’s the definition of young and healthy?
      - arcticbull 7y ago
        I mean, I’ve been saying this for a while and I don’t want to tire y’all out but, young being defined as under 40 and healthy being defined as without comorbid conditions. The median age of the dead in Italy is 80.5 and 99.2% of them were sick, averaging 3 comorbid conditions [3]. So basically the opposite of that. [1] https://twitter.com/AndyBiotech/status/1241741127205572609?s=20 https://twitter.com/AndyBiotech/status/1241741127205572609?s... [2] https://www.cdc.gov/mmwr/volumes/69/wr/mm6912e2.htm https://www.cdc.gov/mmwr/volumes/69/wr/mm6912e2.htm [3] https://www.google.com/amp/s/www.bloomberg.com/amp/news/articles/2020-03-18/99-of-those-who-died-from-virus-had-other-illness-italy-says https://www.google.com/amp/s/www.bloomberg.com/amp/news/arti...
roenxi 7y ago
This is evidence; it isn't great but it also isn't conclusive. We'll need to wait longer for something a little more decisive. A twitter link is also unhelpful because we only get a blurry abstract to go off. The happy dream is maybe hydroxychloroquine has prophylactic tendencies since it is something people can take long term to be at a substantially lower risk vs catching COVID. The abstract doesn't really show much either way on that front. Spitballing as an amateur, I suspect once someone has actual symptoms or is verging on a serious case it is too late to help - what is a drug supposed to do, regrow a busted lung? It comes to a point where the virus isn't what is killing you, it is the damage the virus did while breeding and/or the immune system overreacting fighting back and going haywire. Antivirals should help but aren't expected to be magic for either of those things.
- deleted 7y ago
  [deleted]
- chimichangga 7y ago
  Covid-19: India Recommends Hydroxychloroquine As Prophylaxis For Healthcare Providers, Patient Family Members https://swarajyamag.com/insta/covid-19-india-recommends-hydroxychloroquine-as-prophylaxis-for-healthcare-providers-patient-family-members https://swarajyamag.com/insta/covid-19-india-recommends-hydr...
- antonvs 7y ago
  > The happy dream is maybe hydroxychloroquine has prophylactic tendencies since it is something people can take long term to be at a substantially lower risk vs catching COVID. It's an immune system inhibitor, so this seems like a bad plan.
  - rdtsc 7y ago
    > It's an immune system inhibitor, so this seems like a bad plan. Not unless the cytokine storm is what ends up killing the patient in the end. https://www.vox.com/2020/3/12/21176783/coronavirus-covid-19-deaths-china-treatment-cytokine-storm-syndrome https://www.vox.com/2020/3/12/21176783/coronavirus-covid-19-... Then it may be a good idea. The immune system is a very complex _system_ so some parts may be active and some parts suppressed at the same time and that may be what’s need for the fastest recovery.
deleted 7y ago
[deleted]
cycrutchfield 7y ago
Thank goodness that we are actually getting some RCT results. There has been a huge confirmation bias towards any positive results for chloroquine, no matter how specious or flawed the underlying science was. Everybody wants this to work because the drug is well-tested on humans, cheap, and broadly available. It would be a panacea, a miracle drug. My concern is that the desire for this drug to be effective has clouded people's judgment (even seasoned researchers) and led to bad science.
- neuronic 7y ago
  Don't forget the time pressure. It's a real balance act. The ideal panacea would be an already approved drug that is easy to manufacture, scale and distribute. If fighting covid means we need new drugs then we look at a long development time that will likely stretch the availability of a therapeutic behind the availability of a vaccine. Obviously everyone knows that these things are needed NOW, all bureaucratic road blocks are removed save the really important and necessary ones. You cannot just hand out a drug to millions of people or inject them with vaccines without thoroughly testing their safety first. Imagine if the "cure" to covid was long term harmful in a broad population, e.g. it affects 5% of the people negatively. The health, societal and economic impact could wipe the floor with covid.
- whatshisface 7y ago
  >It would be a panacea, a miracle drug. Not really, a panacea is a drug that cures everything. If chloroquine was found to be an effective antiviral, it would only be a drug that cured two things. That's common enough to not warrant excessive skepticism taken alone.
  - TheAdamAndChe 7y ago
    While that may be the precise definition of a panacea, the vernacular definition is a breakthrough or unexpected good thing.
- jplayer01 7y ago
  This study really isn’t sufficient proof for anything. Not even weak evidence. We need far better studies before deciding to give up on a drug.
sanxiyn 7y ago
Here is actual publication: http://www.zjujournals.com/med/EN/10.3785/j.issn.1008-9292.2020.03.03 http://www.zjujournals.com/med/EN/10.3785/j.issn.1008-9292.2...
JetBen 7y ago
This study comes from China, which lies about everything, so the results cannot be trusted. Chinese gov't likely strong-armed the results as part of their misinformation campaign. They have lied about literally every other stat - why would they tell the truth about this?
fourcolordeck 7y ago
It's two samples of 15. 13/15 and 14/15 successes. Much too small to draw any conclusions. It's even noted a larger sample size is needed
microcolonel 7y ago
It seems like the study was conducted on the complete wrong set of patients.
hannob 7y ago
Has anyone found the study they're talking about? This tweet is only a screenshot of the abstract. And the trials registry entry says "No results published": https://clinicaltrials.gov/ct2/show/NCT04261517 https://clinicaltrials.gov/ct2/show/NCT04261517 Update: I asked the person on twitter and here it is: http://subject.med.wanfangdata.com.cn/UpLoad/Files/202003/43f8625d4dc74e42bbcf24795de1c77c.pdf http://subject.med.wanfangdata.com.cn/UpLoad/Files/202003/43... Apparently it's in chinese.
- ankushnarula 7y ago
  Yes. Two issues... Median age for the control group and test group was 24yrs and 18yrs respectively. This isn't the ideal sample group for testing this drug for COVID-19 indication. But more importantly... Dosing was only 400mg once per day versus recommended 500mg twice per day as performed in the French trial. Taken together, this trial tells us very little on how this drug would perform at proper dosing on severe subjects in vulnerable age range and/or with prior co-morbidities.
stevespang 7y ago
Aneesh Karve @akarve · 9h Replying to @gcbioinv The reported dosage is less than half what the Chinese Government recommends (500mg x 2 (BID Chloroquine)). So it's possible that they didn't hit the effective dose.
hampelm 7y ago
Why are we amplifying someone posting a compressed jpeg to 3,000 followers who lists no name, has a photo of George Costanza, and claims to be a virologist?
- AbrahamParangi 7y ago
  The best early information was on 4chan while the authoritative sources were downplaying it. Pseudo anonymous social media has most of the chaff but all of the wheat.
- bdcravens 7y ago
  Perhaps they are infinitely more qualified than some of the public figures pushing this treatment as a "game-changer"? Either way, hopefully we'll hear from some well-identified, qualified experts in time.
known 7y ago
In late January 2020 during the 2019–20 coronavirus outbreak, Chinese medical researchers stated that exploratory research into chloroquine and two other medications, remdesivir and lopinavir/ritonavir, seemed to have "fairly good inhibitory effects" on the SARS-CoV-2 virus, which is the virus that causes COVID-19. Requests to start clinical testing were submitted.[43] Chloroquine had been also proposed as a treatment for SARS, with in vitro tests inhibiting the SARS-CoV virus.[44][45] However, at least one case of self-medication with chloroquine for COVID-19 has caused a fatality, and the Nigeria Centre for Disease Control has stated that such self-medication "will cause harm and can lead to death." Chloroquine has been recommended by Chinese, South Korean and Italian health authorities for the treatment of COVID-19.[47][48] These agencies noted contraindications for people with heart disease or diabetes.[49] Both chloroquine and hydroxychloroquine were shown to inhibit SARS-CoV-2 in vitro, but a further study concluded that hydroxychloroquine was more potent than chloroquine, with a more tolerable safety profile.[50] Preliminary results from a trial suggested that chloroquine is effective and safe in COVID-19 pneumonia, "improving lung imaging findings, promoting a virus-negative conversion, and shortening the disease course."[51] Self-medication with chloroquine has caused one known fatality. https://en.wikipedia.org/wiki/Chloroquine#COVID-19 https://en.wikipedia.org/wiki/Chloroquine#COVID-19

199 points by aaavl2821 7y ago

didnt find a link to the abstract, seems the results are just being published link to the trial on clinicaltrials.gov is here: https://clinicaltrials.gov/ct2/show/NCT04261517 https://clinicaltrials.gov/ct2/show/NCT04261517 patients in both tx and control arm fared better than in the french study from earlier this week, suggesting patients were healthier / lower risk at baseline patients got slightly lower dose in this study (400 mg / day) vs the french study (600 mg / day)

hartator 7y ago
Kind of crazy these are not in the open. Especially when we are used to work in software.
- aaavl2821 7y ago
  It may be that they just presented an abstract and the manuscript has not yet been submitted for publication or peer reviewed
  - hartator 7y ago
    Well let's peer review this wikipedia-style. Not sure why academia is stuck in last century.
    - aaavl2821 7y ago
      scientists have increasingly been doing this during covid by publishing on biorxiv and then discussing on other channels (twitter etc) for ex, this paper [0] by UCSF analyzing 26 of the 29 viral proteins expressed by the virus was posted on biorxiv and publicized further via twitter [1]. they identified 69 FDA approved drugs that target these proteins, giving the medical and scientific community a massive head start on studying drugs that could potentially be near-term treatments there are some parts of academic science that are stuck in the last century but scientists themselves are certainly not for those interested in learning more about how science works and how scientists operate, the covid situation is a great way to see how its done. modern science is amazing [0] https://www.biorxiv.org/content/10.1101/2020.03.22.002386v1 https://www.biorxiv.org/content/10.1101/2020.03.22.002386v1 [1] https://twitter.com/kevansf/status/1241936588164063233 https://twitter.com/kevansf/status/1241936588164063233
      - raphlinus 7y ago
        Yeah, I'm following a bunch of scientists on Twitter and have been watching from the sidelines with awe and admiration. The contrast to the seeming hordes of dumbfucks could hardly be more remarkable; sometimes it's hard to keep in mind the same platform is host to both sets of people.
        godzulu 7y ago
        This Doctor in NY seems to have had great results so far https://www.thegatewaypundit.com/2020/03/stunning-ny-doctor-vladimir-zelenko-finds-100-success-rate-in-350-patients-using-hydroxychloroquine-with-z-paks-video/ https://www.thegatewaypundit.com/2020/03/stunning-ny-doctor-... This Doctor, Health Commissioner of NYC, Oxiris Barbot, seemed to take a lot of joy in proclaiming: Today our city is celebrating the #LunarNewYear parade in Chinatown, a beautiful cultural tradition with a rich history in our city. I want to remind everyone to enjoy the parade and not change any plans due to misinformation spreading about #coronavirus. https://on.nyc.gov/377LlcH https://on.nyc.gov/377LlcH https://t.co/bwCnIb7j8H https://t.co/bwCnIb7j8H Which Dr deserves awe and admiration and which brings with the seeming hordes of dumbfucks? https://www.amny.com/editorial/city-leaders-seek-to-allay-fears-of-coronavirus-in-chinatown/ https://www.amny.com/editorial/city-leaders-seek-to-allay-fe...
        arcticbull 7y ago
        > This Doctor in NY seems to have had great results so far https://www.thegatewaypundit.com/2020/03/stunning-ny-doctor-.. https://www.thegatewaypundit.com/2020/03/stunning-ny-doctor-.... Let's stick with legitimate news sources. Either way no data is provided there, but the case fatality rate for folks under 10 is 0% and under 29 is between 0.1% and 0%. If this hypothetical doctor even exists, it wouldn't be hard to pick 350 people, give them some HCQ and Azithromycin and have 100% of them recover -- as they would have even if they hadn't received anything. That's more or less what this study shows. In fact, as the fatality rate for under-29s is 0.1%, you have a 70% ((1-0.001)^12) chance that any randomly selected 350 of them will recover.
        raphlinus 7y ago
    - im3w1l 7y ago
      Wikipedia style is unreliable. I'm aware of quite a few errors. Why I don't fix them then? Because my edits would be reverted. Or because the page has been locked. Academic literature in contrast, has multiple parallel journals. If one is suppressing you, you can go to the next. Of course if you go to a less reliable one, then people might not trust your research.
raphlinus 7y ago
Someone on the Twitter thread linked to this, which seems to be not exactly the same document but contains very similar text in the abstract: http://subject.med.wanfangdata.com.cn/UpLoad/Files/202003/43f8625d4dc74e42bbcf24795de1c77c.pdf http://subject.med.wanfangdata.com.cn/UpLoad/Files/202003/43... I think it helps if you can read Chinese, though Google Translate seems to do a pretty ok job on it.
- HarryHirsch 7y ago
  No need to read Chinese, the abstract is on page 2. Conclusion: at current trial size no better than placebo. More study is needed to tease out an effect, if there is any.
  - rurban 7y ago
    It does help if you read the translation. By now everybody should know that the successful dosis is 2x500mg per day for 10 days. Not 1x 400mg per day, which is the old dosis for Malaria prevention. This dosis needs at least 2-3 weeks to be effective (saturate the cell membranes with zinc), and by then the infection is already over. And the Chinese treatment plan contained much more. A study with zero value.
    - newsbinator 7y ago
      What's the source of this?
      - rurban 7y ago
        The official chinese treatment recommendation. https://old.reddit.com/r/COVID19/comments/fd28s6/preprint_article_from_the_shanghai_medical/ https://old.reddit.com/r/COVID19/comments/fd28s6/preprint_ar... Amongst doctors both hydroxychloroquine sulfate and chloroquine phosphate run under broadband antiviral.

JohnJamesRambo 7y ago

> That was a first run trial without the Zpak. The following trial with both showed 100% efficacy after 5-6 days. Is that twitter reply accurate?

sfteus 7y ago
No, that trial has some glaring flaws. Several threads go into them way better than I could. https://twitter.com/GaetanBurgio/status/1241201751916568576 https://twitter.com/GaetanBurgio/status/1241201751916568576 https://twitter.com/MicrobiomDigest/status/1241429544847863808 https://twitter.com/MicrobiomDigest/status/12414295448478638...
- JohnJamesRambo 7y ago
  Thank you for the links! I didn’t know about those gremlins in the supplementary info. Hopefully the WHO trials recently announced will give us a better answer soon.
Khelavaster 7y ago
Both trials have glaring flaws: they're tiny.
- sfkdjf9j3j 7y ago
  What's wrong with the size of the 30 patient experiment?
  - cycrutchfield 7y ago
    The French study? Aside from the fact that it wasn't a randomized study and 6 patients dropped out from the treatment group (1 died, 3 went to ICU)?
  - sfteus 7y ago
    30 patients would be statistically significant. Problem is that they were non randomized, open-label, and they seemingly discarded some of the bad results. They also measured viral load, not cure, and the measurement was not done correctly in all cases. It's basically a "there could potentially be a causal link here; needs way more research" type of study.

HarryHirsch 7y ago

Not unexpected. A week or two ago a Chinese treatment protocol made the rounds where hydroxychloroquine was suggested as an alternative to HIV protease inhibitors. Since we now know that ritonavir/lopinavir doesn't work well, one wouldn't expect hydroxychloroquine to do any better. If it had remarkable clinical effects it would be the first-line treatment.

akarve 7y ago

The reported dosage is less than half what the Chinese Government recommends (500mg x 2 (BID)). So it's possible that they didn't hit the effective dose. https://medium.com/@balajis/the-official-chinese-government-guide-to-diagnosing-and-treating-the-novel-coronavirus-9d06868f8df4 https://medium.com/@balajis/the-official-chinese-government-...

hcknwscommenter 7y ago
your link is to chloroquine phosphate, which has a phosphate group and is only like 75% chloroquine by weight. So no, not less than half. Moreover, you are trying to compare a hydroxychloroquine dose with a chloroquine phosphate dose (active ingredient is chloroquine, not hydroxychloroquine), which is any one's guess if they even have the same mechanism of action here. Just because they both work against malaria, doesn't mean much about this virus. All in all, it is nearly useless to compare the chloroquine phosphate dose and outcomes to the hydroxychloroquine dose and outcomes.
- tzjmetron 7y ago
  Pertinent.

mirimir 7y ago

Wait. I thought that hydroxychloroquine was hypothesized to protect against wet lung, as an anti-inflammatory, and not as an antiviral. Did I just make that up?

rurban 7y ago
No, HCQ is the Antiviral. Anti-inflammatories are also in the plan, but not Iboprofen.
- arcticbull 7y ago
  Not exactly. HCQ has anti-inflammatory action as well as immune moderating action [1] the latter of which may help protect against cytokine storm which occurs in some serious COVID-19 infections. It also has antiviral action in some situations but it's not clear that that's actually relevant to COVID-19 yet. [1] https://en.wikipedia.org/wiki/Hydroxychloroquine https://en.wikipedia.org/wiki/Hydroxychloroquine
  - mirimir 7y ago
    Thanks. Upon reflecting, I meant to say immune moderating as well as anti-inflammatory. Which is why it's become so popular for treating arthritis. I wonder about the antiviral activity, though. What I've read is about possibly faster drop in virus levels. And I suppose that HCQ could be interfering with some stage of intracellular virus production. But time will tell.
    - rurban 7y ago
      You're mixing it up: CQ Phosphat is the rheuma/arthritis treatment, HCQ Sulfat the malaria prevention drug. CQ has much more severe side-effects, esp. in blacks. HCQ can lead to temporal blindness after years of use. We are talking 10 days here.

nikolay 7y ago

I am sorry, but isn't the mechanism of action that hydroxychloroquine is simply a zinc ionophore, i.e. you need enough free zinc in the blood for this to work? I read doctors suggesting using hydroxychloroquine along with 50mg of ionic zinc.

Reelin 7y ago
CQ (and HCQ, etc) have multiple potential mechanisms of action. I don't believe we know how it works in this particular case yet, or if it even works at all. It is indeed a zinc ionophore, [1] and those are known to impair the replication of a number of RNA viruses. [2] However, there are a number of other mechanisms at play here as well. [3] > Both CQ and HCQ are weak bases that are known to elevate the pH of acidic intracellular organelles, such as endosomes/lysosomes, essential for membrane fusion5. In addition, CQ could inhibit SARS-CoV entry through changing the glycosylation of ACE2 receptor and spike protein6. Time-of-addition experiment confirmed that HCQ effectively inhibited the entry step, as well as the post-entry stages of SARS-CoV-2, which was also found upon CQ treatment (Supplementary Fig. S2). [1] https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0109180 https://journals.plos.org/plosone/article?id=10.1371/journal... [2] https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1001176 https://journals.plos.org/plospathogens/article?id=10.1371/j... [3] https://www.nature.com/articles/s41421-020-0156-0 https://www.nature.com/articles/s41421-020-0156-0
omgwtfbyobbq 7y ago
Like Reelin said, it's effectiveness may be related to it's ability to modulate immune activity by affecting pH. https://www.ncbi.nlm.nih.gov/pubmed/27927040 https://www.ncbi.nlm.nih.gov/pubmed/27927040 Course, that'll only work if the symptoms are being caused by an overactive immune system and it's able to mediate that immune response in time.
- deleted 7y ago
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- arcticbull 7y ago
  > Course, that'll only work if the symptoms are being caused by an overactive immune system and it's able to mediate that immune response in time. Accumulating evidence suggests that a subgroup of patients with severe COVID-19 might have a cytokine storm syndrome [1]. HCQ is known to moderate this reaction. [1] https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30628-0/fulltext https://www.thelancet.com/journals/lancet/article/PIIS0140-6...

djvu9 7y ago

It is a 30 patients test and almost everybody’s fever was gone right after enrollment. Even the swab test results turned negative in 2-4 days. Why is medicine ever needed for such group of patients?

jansan 7y ago
The results are disappointing because they are useless. That's how I interpret the headline.

throwaway5466 7y ago

For people that didn't read: it's "disappointing" because both the control and study groups largely tested negative (93% and 87% respectively). That 87% figure sounds worse than the control but it actually is better than in the French study. What happened in essence is that almost all cases were mild so the patients almost all got better after a while, with or without medication. This doesn't mean HCQ is ineffective, only that its efficacy couldn't be measured in this instance. And I wouldn't call a study where almost everyone gets better at the end "disappointing".

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cycrutchfield 7y ago
It's disappointing because it's no better than placebo.
- arcticbull 7y ago
  In this case (as with many others) placebo is pretty effective, but also, these folks didn't get sick enough to need it, as with the overwhelming majority of young and healthy people. Another, broader study is required. I'm sure we'll find out more soon -- this reads like a mulligan though.
  - dajohnson89 7y ago
    any data on what percentage of “young healthy” people die/get hospitalized? also, what’s the definition of young and healthy?
    - arcticbull 7y ago
      I mean, I’ve been saying this for a while and I don’t want to tire y’all out but, young being defined as under 40 and healthy being defined as without comorbid conditions. The median age of the dead in Italy is 80.5 and 99.2% of them were sick, averaging 3 comorbid conditions [3]. So basically the opposite of that. [1] https://twitter.com/AndyBiotech/status/1241741127205572609?s=20 https://twitter.com/AndyBiotech/status/1241741127205572609?s... [2] https://www.cdc.gov/mmwr/volumes/69/wr/mm6912e2.htm https://www.cdc.gov/mmwr/volumes/69/wr/mm6912e2.htm [3] https://www.google.com/amp/s/www.bloomberg.com/amp/news/articles/2020-03-18/99-of-those-who-died-from-virus-had-other-illness-italy-says https://www.google.com/amp/s/www.bloomberg.com/amp/news/arti...

roenxi 7y ago

This is evidence; it isn't great but it also isn't conclusive. We'll need to wait longer for something a little more decisive. A twitter link is also unhelpful because we only get a blurry abstract to go off. The happy dream is maybe hydroxychloroquine has prophylactic tendencies since it is something people can take long term to be at a substantially lower risk vs catching COVID. The abstract doesn't really show much either way on that front. Spitballing as an amateur, I suspect once someone has actual symptoms or is verging on a serious case it is too late to help - what is a drug supposed to do, regrow a busted lung? It comes to a point where the virus isn't what is killing you, it is the damage the virus did while breeding and/or the immune system overreacting fighting back and going haywire. Antivirals should help but aren't expected to be magic for either of those things.

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chimichangga 7y ago
Covid-19: India Recommends Hydroxychloroquine As Prophylaxis For Healthcare Providers, Patient Family Members https://swarajyamag.com/insta/covid-19-india-recommends-hydroxychloroquine-as-prophylaxis-for-healthcare-providers-patient-family-members https://swarajyamag.com/insta/covid-19-india-recommends-hydr...
antonvs 7y ago
> The happy dream is maybe hydroxychloroquine has prophylactic tendencies since it is something people can take long term to be at a substantially lower risk vs catching COVID. It's an immune system inhibitor, so this seems like a bad plan.
- rdtsc 7y ago
  > It's an immune system inhibitor, so this seems like a bad plan. Not unless the cytokine storm is what ends up killing the patient in the end. https://www.vox.com/2020/3/12/21176783/coronavirus-covid-19-deaths-china-treatment-cytokine-storm-syndrome https://www.vox.com/2020/3/12/21176783/coronavirus-covid-19-... Then it may be a good idea. The immune system is a very complex _system_ so some parts may be active and some parts suppressed at the same time and that may be what’s need for the fastest recovery.

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cycrutchfield 7y ago

Thank goodness that we are actually getting some RCT results. There has been a huge confirmation bias towards any positive results for chloroquine, no matter how specious or flawed the underlying science was. Everybody wants this to work because the drug is well-tested on humans, cheap, and broadly available. It would be a panacea, a miracle drug. My concern is that the desire for this drug to be effective has clouded people's judgment (even seasoned researchers) and led to bad science.

neuronic 7y ago
Don't forget the time pressure. It's a real balance act. The ideal panacea would be an already approved drug that is easy to manufacture, scale and distribute. If fighting covid means we need new drugs then we look at a long development time that will likely stretch the availability of a therapeutic behind the availability of a vaccine. Obviously everyone knows that these things are needed NOW, all bureaucratic road blocks are removed save the really important and necessary ones. You cannot just hand out a drug to millions of people or inject them with vaccines without thoroughly testing their safety first. Imagine if the "cure" to covid was long term harmful in a broad population, e.g. it affects 5% of the people negatively. The health, societal and economic impact could wipe the floor with covid.
whatshisface 7y ago
>It would be a panacea, a miracle drug. Not really, a panacea is a drug that cures everything. If chloroquine was found to be an effective antiviral, it would only be a drug that cured two things. That's common enough to not warrant excessive skepticism taken alone.
- TheAdamAndChe 7y ago
  While that may be the precise definition of a panacea, the vernacular definition is a breakthrough or unexpected good thing.
jplayer01 7y ago
This study really isn’t sufficient proof for anything. Not even weak evidence. We need far better studies before deciding to give up on a drug.

sanxiyn 7y ago

Here is actual publication: http://www.zjujournals.com/med/EN/10.3785/j.issn.1008-9292.2020.03.03 http://www.zjujournals.com/med/EN/10.3785/j.issn.1008-9292.2...

JetBen 7y ago

This study comes from China, which lies about everything, so the results cannot be trusted. Chinese gov't likely strong-armed the results as part of their misinformation campaign. They have lied about literally every other stat - why would they tell the truth about this?

fourcolordeck 7y ago

It's two samples of 15. 13/15 and 14/15 successes. Much too small to draw any conclusions. It's even noted a larger sample size is needed

microcolonel 7y ago

It seems like the study was conducted on the complete wrong set of patients.

hannob 7y ago

Has anyone found the study they're talking about? This tweet is only a screenshot of the abstract. And the trials registry entry says "No results published": https://clinicaltrials.gov/ct2/show/NCT04261517 https://clinicaltrials.gov/ct2/show/NCT04261517 Update: I asked the person on twitter and here it is: http://subject.med.wanfangdata.com.cn/UpLoad/Files/202003/43f8625d4dc74e42bbcf24795de1c77c.pdf http://subject.med.wanfangdata.com.cn/UpLoad/Files/202003/43... Apparently it's in chinese.

ankushnarula 7y ago
Yes. Two issues... Median age for the control group and test group was 24yrs and 18yrs respectively. This isn't the ideal sample group for testing this drug for COVID-19 indication. But more importantly... Dosing was only 400mg once per day versus recommended 500mg twice per day as performed in the French trial. Taken together, this trial tells us very little on how this drug would perform at proper dosing on severe subjects in vulnerable age range and/or with prior co-morbidities.

stevespang 7y ago

Aneesh Karve @akarve · 9h Replying to @gcbioinv The reported dosage is less than half what the Chinese Government recommends (500mg x 2 (BID Chloroquine)). So it's possible that they didn't hit the effective dose.

hampelm 7y ago

Why are we amplifying someone posting a compressed jpeg to 3,000 followers who lists no name, has a photo of George Costanza, and claims to be a virologist?

AbrahamParangi 7y ago
The best early information was on 4chan while the authoritative sources were downplaying it. Pseudo anonymous social media has most of the chaff but all of the wheat.
bdcravens 7y ago
Perhaps they are infinitely more qualified than some of the public figures pushing this treatment as a "game-changer"? Either way, hopefully we'll hear from some well-identified, qualified experts in time.

known 7y ago

In late January 2020 during the 2019–20 coronavirus outbreak, Chinese medical researchers stated that exploratory research into chloroquine and two other medications, remdesivir and lopinavir/ritonavir, seemed to have "fairly good inhibitory effects" on the SARS-CoV-2 virus, which is the virus that causes COVID-19. Requests to start clinical testing were submitted.[43] Chloroquine had been also proposed as a treatment for SARS, with in vitro tests inhibiting the SARS-CoV virus.[44][45] However, at least one case of self-medication with chloroquine for COVID-19 has caused a fatality, and the Nigeria Centre for Disease Control has stated that such self-medication "will cause harm and can lead to death." Chloroquine has been recommended by Chinese, South Korean and Italian health authorities for the treatment of COVID-19.[47][48] These agencies noted contraindications for people with heart disease or diabetes.[49] Both chloroquine and hydroxychloroquine were shown to inhibit SARS-CoV-2 in vitro, but a further study concluded that hydroxychloroquine was more potent than chloroquine, with a more tolerable safety profile.[50] Preliminary results from a trial suggested that chloroquine is effective and safe in COVID-19 pneumonia, "improving lung imaging findings, promoting a virus-negative conversion, and shortening the disease course."[51] Self-medication with chloroquine has caused one known fatality. https://en.wikipedia.org/wiki/Chloroquine#COVID-19 https://en.wikipedia.org/wiki/Chloroquine#COVID-19