10 ms·

Chloroquine trial halted after 11 patients die on high dose

174 points by colinprince 7y ago

GenerocUsername 7y ago
From the article: "The Brazil study was undertaken with 81 patients at a hospital in Manaus, in Amazonas state. As well as chloroquine, patients were also given azithromycin, an antibiotic also being used in the U.S., often paired with chloroquine. However, higher dose use of chloroquine (600 milligrams as opposed to 450 milligrams) was stopped after just six days, after 11 of patients who were given the greater dose died." So they canceled a test with higher doses, not tests with regular doses. Meanwhile they touched several times on the fact that Trump touted the drug. If trump recommended hugs, the media would write an article about how choking people is bad.
- nick_kline 7y ago
  It's not that trump said he likes to breath air, so everyone became fixated on that. It's that this is one of many (dozens at least) of things he has said were solutions, cures, miracles that would deal with covid-19. These went through the fox news world and now my elderly relatives are fixated on getting it (they are otherwise healthy). Because fox news and all these other non-medical people keep harping on it, the elderly people, the same ones preyed upon by certain news sources get the wrong idea about this.
  - complianceowl 7y ago
    Wrong (Trump Voice)
  - ghostpepper 7y ago
    There are two stories here: One is whether one of the most promising drugs to stop the pandemic is actually dangerous, and the other is what Trump said and whether he was right to say it blah blah blah. Thanks to the inclusion of Trump in this article by National Post, anyone who has strong views about Trump (most people in North America) are now focused on the second story, instead of the first.
    - m0zg 7y ago
      Best I can tell, the article doesn't even mention the cause of death. :-) Did they die because they were given HCQ or did they die in spite of being given HCQ? We'll never know. And the paper itself (https://web.archive.org/web/20200413181618/https://www.medrxiv.org/content/10.1101/2020.04.07.20056424v1.full.pdf https://web.archive.org/web/20200413181618/https://www.medrx...) doesn't say that either, and mentions that this study's randomization was flawed in that older patients with heart disease were assigned to the high dosage arm of the experiment.
      - tehjoker 7y ago
        They saw people were getting heart arrhythmias in the original Brazil study. Anecdotally, a doctor I know has been seeing an increase in arrhythmias on patients treated with HCQ at lower doses if they already have a pre-existing circulatory problem. What is really irking me is that we still don't even know if it's really doing anything. At the same time, my elderly parent is taking HCQ for arthritis and appears to think she is invincible, going to the store each day in the middle of Queens, the world epicenter. She tried to send me links to Trump's touted Dr. Zelenko about how it's a miracle cure.
        m0zg 7y ago
        We don't even know if eggs and butter are "good for you" so I'm not surprised we know jack squat about HCQ beyond anecdotal evidence, which most studies you will find in the press seem to either ignore, or set their studies up s.t. they fail. In particular, per anecdotal evidence HCQ+Zpak+Zinc is the most effective combination, and only if given at the onset of symptoms. Yet routinely we see either just HQ or HCQ alone, or HCQ (with or without Zpak) given to patients that are so far gone it's unlikely to make any difference. Just read the original study fer chrissakes, it's publicly accessible. Sure it's not "randomized" or "principled", but at the very least _try_ what Raoult did in the first place, maybe? Exactly as he did it?
        tehjoker 7y ago
        It looks like Azithromycin is for clearing bacterial pneumonia. Certainly this is a possible and probably common complication of viral pneumonia caused by COVID-19, but I'm sure doctors are well aware of ways to treat secondary bacterial pneumonia. Just looking at what doctors are saying about Zinc, it seems like there could be something to it, especially if an individual is Zinc deficient, but it's not at all clear it's anything like a silver bullet. https://www.medicinenet.com/script/main/art.asp?articlekey=228691 https://www.medicinenet.com/script/main/art.asp?articlekey=2... We have no idea what the mechanism of action if for HCQ. My doctor friend tried looking it up and it seemed like there are many possible pathways, many of which are still being researched, that modify immune response. There was one statement that speculated if HCQ could act directly on viral particles by changing pH near a key molecule. My attitude is, great if it works, but we still are very far from knowing that for certain. One thing that I think is worth keeping in mind is that if a medicine kills 1% of the people we give it to, and we give it to a large number of people relatively indiscriminately, it's about as bad as COVID, which kills 1-5% of victims (though as much as 15% for high risk patients).
  - addicted44 7y ago
    Any high level official recommending it is a bad thing in itself. The major issue is that there isn't enough evidence there for drug companies to put in money to ramp up supply. Heck, there wasn't enough evidence for Trump, who had just signed a trillion dollar stimulus, to divert a few tens of millions of dollars to ramp up supply. Yet, you are telling a bunch of people who may never be able to make use of it to go buy the existing supply on the market. This existing supply exists because there are people who have actual proven needs of the drug, and as a result now you've also made the drug unavailable for uses where it's actually been proven to work.
  - berryjerry 7y ago
    Sorry to say but this sounds like a Darwin award. People always worry about the stupidest in society but if it wasn't one thing it would be another for them. If the danger of something is that stupid people act stupidly then I don't see it as a danger at all. This is why people can sell cure all homeopathic drinks that only succeed in making you relieve your bowels or "cleanse your body" as they would say. In this case the people are doubly stupid because not only do they believe something wrong, but they believe it wrong not from a lie, but because they are interpreting "promising trials" as something already working.
  - giardini 7y ago
    nick_kline>"and now my elderly relatives are fixated on getting it(HCQ/CQ)." Do you think Trump and Fox News are your elderly relatives only source of information? Do you think this behavior is limited to your elderly relatives? You can't shake an MD today w/o HCQ/CQ, zinc and ZPAK pills falling out of their pockets. Why is that? Firstly, because it works. Secondly, doctors (and dentists, and everyone who could write prescriptions and wasn't living in Tibet) spread the word of using HCQ/CQ+ZINC+ZPAK as a prophylactic measure among themselves. They wrote prescriptions for themselves and theirs, so much so that for awhile they sucked up all the HCQ/CQ in the supply chain. If you think your "elderly relatives" are "fixated", then you must also think that most MDs are also "fixated".But maybe your "elderly relatives" know something you don't know. Perhaps you're the "fixated" one - fixated on false ideas of how to best judge from social behavior in the heat of possible disaster what most likely works and what does not work. In this situation "doing what the doctors are doing" makes sense. The poor lost soul by the side of the road, waving a red flag and saying "But what about randomized controlled double-blind trials? I must have real science!" is the person that Darwin's theories will leave behind.
- xiphias2 7y ago
  It was a multi-drug combination therapy without real control arm as far as I saw. Also the 95% confidence intervals were overlapping, and the probablity of the high dosage being more lethal is not published.
  - brokensegue 7y ago
    So you think they were mistaken to stop the trial? Or what?
    - xiphias2 7y ago
      No, when we are talking about taking away human lives, even with a little bit of data it’s immoral to continue a human trial. The problem is with the binary reporting that doesn’t get into the nuances of the data that we’re getting. People are getting confused and disappointed, because it looks like there’s a new miracle cure every day. And at the end cynical people are wright when it comes to this kind of binary reporting. And then cynism can lead to bad decisions.
- rdtsc 7y ago
  > Meanwhile they touched several times on the fact that Trump touted the drug. I did notice that. There were articles and some research before and everyone seemed interested and noticed as soon as he mentioned it the majority opinion almost immediately switched to "it's dangerous", "let's avoid it", "it probably won't work" while all the other alternatives seem to be still "interesting" and "worth studying" etc.
  - outworlder 7y ago
    > I did notice that. There were articles and some research before and everyone seemed interested and noticed as soon as he mentioned it the majority opinion almost immediately switched to "it's dangerous", "let's avoid it", "it probably won't work" while all the other alternatives seem to be still "interesting" and "worth studying" etc. The fact that a politician is pushing an (yet) unproven drug has to be viewed with skepticism. The flip side is that it caused a cascade of reactions from other governments trying to control the drug's supply. They may have reasoned that a world leader has information they do not. And other governments (see this article) started pushing it as a treatment too. Additionally, now people are pushing the drug as a political issue. By people, I mean the average joe. This is damaging. Regardless, science is doing its thing. Trials are ongoing, as this article shows. But politicians should refrain from making baseless statements about subjects they know zero about.
    - dmix 7y ago
      Notably on Feb 4th China announced their researchers were recommending testing chloroquine, about a month and a half(?) before Trump mentioned it: http://www.whiov.ac.cn/kyjz_105338/202002/t20200204_5497136.html?from=groupmessage http://www.whiov.ac.cn/kyjz_105338/202002/t20200204_5497136.... https://www.nytimes.com/2020/02/06/health/coronavirus-treatments.html https://www.nytimes.com/2020/02/06/health/coronavirus-treatm... https://www.nature.com/articles/s41422-020-0282-0 https://www.nature.com/articles/s41422-020-0282-0 This was the original study which I believe influenced the French study and Dr. Zelenko (who seemed to be the nexus to Trump). The UK banned export of CQ around Feb 26th (I believe the first country to do so): https://ihsmarkit.com/research-analysis/uk-bans-parallel-export-of-two-covid19-treatment-candidates.html https://ihsmarkit.com/research-analysis/uk-bans-parallel-exp... From Google's custom date searches is looks like Trump first mentioned it in a press conference on March 19th: https://twitter.com/cspan/status/1240672025989001221 https://twitter.com/cspan/status/1240672025989001221
hinkley 7y ago
When this clusterfuck first started revealing itself, the forsythia plants in my town had just started flowering. Every time this chloroquine stuff comes up I just hear Jude Law's character from Contagion in my head saying "forsythia" over and over again in different sentence fragments. Unfortunately the SEC isn't going to send men to arrest anybody this time.
- klenwell 7y ago
  I had the same thought. Here's the clip from Contagion where Jude Law's character, an internet crank, promotes it on national television: https://www.youtube.com/watch?v=CHZ8wx6J36Q https://www.youtube.com/watch?v=CHZ8wx6J36Q
  - scared2 7y ago
    Super interesting. It seems that everything is premeditated.
  - andy_ppp 7y ago
    Man I really need to watch Contagion then...
    - ornornor 7y ago
      It’s interesting watching it now. I watched it last month and it felt like it was a documentary for what hasn’t happened yet in this epidemics.
      - libria 7y ago
        1 year ago, I'd have thought this movie was typical Hollywood hyperbole. Watching it recently, the scene where Sanjay Gupta is facilitating an interview about the virus was like deja vu. He was literally on TV doing the same thing recently, but for real this time.
      - calyth2018 7y ago
        The only problem is that the vaccine scene won't play out that way in real life. Otherwise Contagion is actually quite accurate.
bearcobra 7y ago
COVID-19 is obviously very scary and I fully understand why we'd want to lessen some restrictions to allow novel treatments to be tried. But as bad as things are, I think people underestimate how much worse they could be if aren't careful when easing those restrictions. There seems to be a mentality that people are going to die anyway so we should be trying anything. That seems to underestimate the potential to make things worse, not just in terms of deaths but also in terms of quality of life for patients.
- dionian 7y ago
  This is why FDA is not recommending it as a treatment for everyone, only off-label.
  - 0xff00ffee 7y ago
    Here's some clarification I googled because I was a little confused by your comment: TL;DR - The FDA only approved it for emergency investigation, not treatment. (as of 2020-03-31): https://www.forbes.com/sites/rachelsandler/2020/03/30/fda-approves-anti-malarial-drugs-chloroquine-and-hydroxychloroquine-for-emergency-coronavirus-treatment/#3d0c01045e5d https://www.forbes.com/sites/rachelsandler/2020/03/30/fda-ap...
ph0rque 7y ago
It irks me to see chloroquine and hydroxychloroquine being used interchangeably in the media. This study used chloroquine. Trump touted hydroxychloroquine. "Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro" https://www.nature.com/articles/s41421-020-0156-0 https://www.nature.com/articles/s41421-020-0156-0
- Cantbekhan 7y ago
  https://xkcd.com/1217/ https://xkcd.com/1217/
- mattkrause 7y ago
  This particular article is not bad on that front. For example: "The similar drugs chloroquine and hydroxychloroquine have been pushed by Trump as a possible partial solution to the pandemic..." [Folks, the point is not about Trump here. The point is that the article's author clearly knows that CQ and HCQ are separate but related drugs].
  - Florin_Andrei 7y ago
    > pushed by Trump Ah, yes, Trump, the world's leading expert in antiviral medicine. Stop politicizing this issue. Stop feeding the trolls and the demagogues. Let science find things out.
    - mattkrause 7y ago
      That's a verbatim quote from the article, and the point I was trying to make was that the article doesn't conflate them. It says that the drugs are similar (which they are, both chemically and pharmacologically) and have both received some hype. As for "politicizing the issue"...I'm a research scientist (and one who sometimes works with immunologists!). The data on CQ/HCQ make it look useless to me. The good trials show garbage effects and only the garbage "trials" seem to show any results. If you think insisting on careful analysis of data is political...good luck to you.
- 7y ago
jonplackett 7y ago
This is this the more toxic variant though right? It’s meant to be hydroychloroquine
- simtel20 7y ago
  Here in Brazil, for whatever reason, the president has been talking up chloroquine, while Trumps talking point is hydroxychloroquine. I don't know how people who have no medical training or experience who are actively trying to undermine their advisors with such experience determine which of these medicines they're going to place their bets on, but given the lack of good results in either, it seems like either bet is as bad as the other.
  - goldcd 7y ago
    Like Pepsi and Coke?
    - jcrubino 7y ago
      Like Coke and Diet Coke and Coke Zero
  - merpnderp 7y ago
    China had more luck treating COVID with chloroquine phosphate (which is more toxic), but hydrochloroquine sulfate is more available in the US.
    - addicted44 7y ago
      COVID-19 kills anywhere between 0.7-4% of the people it infects. (Some countries like Italy saw a much higher mortality rate, nearing 15% in Italy, I believe, but that was due to the breakdown of the overwhelmed health services). How would one even tell if any of the chloroquinine derivatives have been effective without a systematic study when 96 out of 100 people (at worst) would have recovered anyways? That's another thing that makes the 20 person French study which kicked off all this so much more ridiculous. There was a 44% chance that they would have all recovered without any intervention. But it was probably higher for this group since they did have intervention, and they clearly had a high level of medical assistance.
Carpetsmoker 7y ago
Also interesting read on some more background of the drug: https://blogs.sciencemag.org/pipeline/archives/2020/03/20/chloroquine-past-and-present https://blogs.sciencemag.org/pipeline/archives/2020/03/20/ch...
tannerbrockwell 7y ago
I wonder what happened with the WHO study: "20,000 healthcare workers [will receive] #chloroquine [and] will be tested daily as currently used in the treatment of rheumatoid arthritis for three months or until they are diagnosed with COVID-19." https://www.who.int/blueprint/priority-diseases/key-action/RD-Blueprint-expert-group-on-CQ-call-Mar-13-2020.pdf https://www.who.int/blueprint/priority-diseases/key-action/R...
- sdenton4 7y ago
  Maybe it will be discontinued, now that the loudest promoter of hydrochloroquine has decided to pull their WHO funding... (The city is on fire! Those hacks at the fire department failed to predict the earthquake! Fire them all!)
Mc_Big_G 7y ago
Fake news. Trump is never wrong /s
tgafpc2 7y ago
Arrhythmia is a well know complication and contraindication of Chloroquine. This should have been identified by the doctors prescribing it and NOT PRESCRIBED IT for at risk patients.
- HillRat 7y ago
  Unfortunately, COVID may also be associated with hypokalemia, so even patients without comorbidities could be at risk for TdP. HCQ may have therapeutic or prophylactic benefits, but it’s definitely not without serious risks.
DoreenMichele 7y ago
I'm going to note this: The body is the landscape where this battle gets fought. "Nuke it from orbit. It's the only way to be sure." is a treatment policy that should be expected to result in some patients dying. Trump has been vociferous on the drugs’ potential benefits, but among those to contradict his views are his own top expert Anthony Fauci Edit: I stand corrected. The above still horrifies me. I've edited out the inaccurate framing. It's absolutely not intended to make replies to me look dumb. Quite the contrary. This comment has been extensively edited. Hopefully, this is the least worst handling of blurting something out that expresses my concerns badly.
- pdonis 7y ago
  > this is being tested not because medical professionals think it's a good idea, but because the US president has been loudly promoting it The article is describing a trial in Brazil, not the US. Also, the trial used chloroquine, not hydroxychloroquine. They're not the same.
  - 12elephant 7y ago
    Furthermore, the studies on chloroquine started at least a month before the US president ever mentioned hydroxycholoroquine in mid March. E.g. this one from early Feb: https://www.nature.com/articles/s41422-020-0282-0 https://www.nature.com/articles/s41422-020-0282-0 So the research is not only being conducted because of the US president's promotion.
rurban 7y ago
Horrible article. Now what was the problem? CQ or HCQ? Major difference in those two.
stevev 7y ago
I think a high dose of any reactive medication or drug is deadly.
- samatman 7y ago
  This is a meaningless statement. For starters, to call a compound "reactive" means it's eager to participate in chemical reactions. I'm unable to discern what you were trying to say, but I'm betting it isn't that. To continue, yes, at the limit, a sufficient dose of anything will kill you. The difference between the therapeutic dose and the lethal dose is referred to as the therapeutic index: wide is good, narrow is dangerous. (hydroxy)chloroquine has a fairly narrow therapeutic index at the doses being tested for acute COVID-19 intervention. That's not a property you want in a medicine. It would have to be that much more effective to make up for the risk it poses to the patient.
- ska 7y ago
  Most everything has an LD50 value but that often doesn't make any practical difference. You can construct scenarios where LD50 of water is relevant, say, but it isn't easy to see them in practice I imagine.
martingoodson 7y ago
This title is misleading. They didn't halt the trial, they halted one treatment arm (the arm with a very high dose). They continued with the 'low' dose (2.7g - about the same dose as used to treat malaria). The high dose was over 4x more of the drug, at 12g.
- post_below 7y ago
  I haven't looked farther than the linked article, but assuming their reporting is accurate: > However, higher dose use of chloroquine (600 milligrams as opposed to 450 milligrams) was stopped after just six days, after 11 of patients who were given the greater dose died. To me that reads as an increase of about 1.35x rather than 4x.
  - bagacrap 7y ago
    600 mg chloroquine twice daily for 10 days or total dose 12g 450 mg for 5 days, twice daily only on the first day, or total dose 2.7 g
    - post_below 7y ago
      That 600mg part of the study ended at 6 days. The potential total dose in a future that didn't happen seems irrelevant.
droithomme 7y ago
They were giving 1.2 grams a day to the patients that died. That is significantly higher than what is known to be a safe dose. CQ is also not indicated for anyone with underlying heart conditions. Since COVID-19 is known to cause heart damage as well as lung damage in the late stage of the disease using these drugs in the late stage of the disease has built in problems. The article doesn't mention anyone in the lower dose group dying of heart problems, though heart attacks and related problems are things that are known to happen to people with COVID-19. The lower dose study is continuing and was not halted. Presumably there will be a subsequent study published with those results. I agree that it is a bad idea to be taking 1.2 grams a day of CQ. During the century of widespread CQ use the fatality rate due to side effects was certainly no where near what they managed to obtain by overdosing patients in this reckless study.
giardini 7y ago
The researchers gave whopping doses of chloroquine to both groups: (a) high dose chloroquine (600 mg chloroquine twice daily for 10 days or total dose 12g); (b) low dose chloroquine (450 mg for 5 days, twice daily only on the first day, or total dose 2.7 g) In addition, all patients received ceftriaxone and azithromycin. So group (a) got 1200 mg chloroquine the first day and group (b) got 900 mg chloroquine the first day. No wonder they had irregular heart rates! Luckily a review board stopped group (a) treatment before they killed all the patients. In contrast, the regimen for Covid-19 _successfully_ used by Dr. Zev Zelenko on ~700 patients is: 1. Hydroxychloroquine 200mg twice a day for 5 days, 2. Azithromycin 500 mg once a day for 5 days, 3. Zinc sulfate 220 mg once a day for 5 days. https://www.freerepublic.com/focus/f-news/3829492/posts https://www.freerepublic.com/focus/f-news/3829492/posts The zinc sulfate is _important_ because it raises the blood level of zinc (Zn++ ion). Chloroquine is a zinc Zn++ "ionophore" which marshals Zn++ across the cell's outer wall into the cytoplasm where the Zn++ can halt viral replication. "Chloroquine Is a Zinc Ionophore": https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4182877/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4182877/ (PDF) https://journals.plos.org/plosone/article/file?id=10.1371/jo.. https://journals.plos.org/plosone/article/file?id=10.1371/jo.... Some researchers seem to be missing the point that chloroquine and its analogs may play a different role here than in malaria, acting not directly against covid-19 but as a facilitator for Zn++, which then halts covid-19 replication. Zelenko's use of an antibiotic(azithromycin = Z-Pak) is a prophylaxis against potential secondary bacterial infection; the antibiotic would not likely play a role against the viral infection directly. Once again we see that randomized, double-blinded clinical trials can be more deadly and less informative than ad-hoc studies performed on the battlefield of medicine.
- cycrutchfield 7y ago
  > In contrast, the regimen for Covid-19 _successfully_ used by Dr. Zev Zelenko on ~700 patients is: For all we know, it was a successful placebo. Anecdotal evidence does not constitute scientific fact.
  - 12elephant 7y ago
    A single piece of anecdotal evidence does not constitute scientific fact. ~700 pieces of anecdotal evidence is a study.
the_mitsuhiko 7y ago
Austria stopped all uses of chloroquine/hydroxychloroquine for covid-19 a few weeks back citing bad outcomes and from what I can tell it's not the only country. I feel like the only reason trials are kept alive are the popularity in the US.
shadowprofile77 7y ago
To be clear, because the title makes it ambiguous, 11 patients died because of the treatment, or 11 paitents died of covid-related/suspected causes despite elevated treatment? It's a crucial distinction. The article doesn't perfectly specify which either. Covid-19 is already becoming known for causing cardiac problems in some patients, so if they were killed by a fatal heart arrhythmia, how to be sure that the medication caused it to be fatal instead of the disease progression itself due to myocarditis or something related combining with said arrhythmia.
lenkite 7y ago
Those dosage numbers are completely OFF the charts. Thats ridiculously high dosage. In India, it's 200mg for treatment of Covid 19. 600mg WILL kill you. I don't even understand who approved that!

174 points by colinprince 7y ago

From the article: "The Brazil study was undertaken with 81 patients at a hospital in Manaus, in Amazonas state. As well as chloroquine, patients were also given azithromycin, an antibiotic also being used in the U.S., often paired with chloroquine. However, higher dose use of chloroquine (600 milligrams as opposed to 450 milligrams) was stopped after just six days, after 11 of patients who were given the greater dose died." So they canceled a test with higher doses, not tests with regular doses. Meanwhile they touched several times on the fact that Trump touted the drug. If trump recommended hugs, the media would write an article about how choking people is bad.

nick_kline 7y ago
It's not that trump said he likes to breath air, so everyone became fixated on that. It's that this is one of many (dozens at least) of things he has said were solutions, cures, miracles that would deal with covid-19. These went through the fox news world and now my elderly relatives are fixated on getting it (they are otherwise healthy). Because fox news and all these other non-medical people keep harping on it, the elderly people, the same ones preyed upon by certain news sources get the wrong idea about this.
- complianceowl 7y ago
  Wrong (Trump Voice)
- ghostpepper 7y ago
  There are two stories here: One is whether one of the most promising drugs to stop the pandemic is actually dangerous, and the other is what Trump said and whether he was right to say it blah blah blah. Thanks to the inclusion of Trump in this article by National Post, anyone who has strong views about Trump (most people in North America) are now focused on the second story, instead of the first.
  - m0zg 7y ago
    Best I can tell, the article doesn't even mention the cause of death. :-) Did they die because they were given HCQ or did they die in spite of being given HCQ? We'll never know. And the paper itself (https://web.archive.org/web/20200413181618/https://www.medrxiv.org/content/10.1101/2020.04.07.20056424v1.full.pdf https://web.archive.org/web/20200413181618/https://www.medrx...) doesn't say that either, and mentions that this study's randomization was flawed in that older patients with heart disease were assigned to the high dosage arm of the experiment.
    - tehjoker 7y ago
      They saw people were getting heart arrhythmias in the original Brazil study. Anecdotally, a doctor I know has been seeing an increase in arrhythmias on patients treated with HCQ at lower doses if they already have a pre-existing circulatory problem. What is really irking me is that we still don't even know if it's really doing anything. At the same time, my elderly parent is taking HCQ for arthritis and appears to think she is invincible, going to the store each day in the middle of Queens, the world epicenter. She tried to send me links to Trump's touted Dr. Zelenko about how it's a miracle cure.
      - m0zg 7y ago
        We don't even know if eggs and butter are "good for you" so I'm not surprised we know jack squat about HCQ beyond anecdotal evidence, which most studies you will find in the press seem to either ignore, or set their studies up s.t. they fail. In particular, per anecdotal evidence HCQ+Zpak+Zinc is the most effective combination, and only if given at the onset of symptoms. Yet routinely we see either just HQ or HCQ alone, or HCQ (with or without Zpak) given to patients that are so far gone it's unlikely to make any difference. Just read the original study fer chrissakes, it's publicly accessible. Sure it's not "randomized" or "principled", but at the very least _try_ what Raoult did in the first place, maybe? Exactly as he did it?
        tehjoker 7y ago
        It looks like Azithromycin is for clearing bacterial pneumonia. Certainly this is a possible and probably common complication of viral pneumonia caused by COVID-19, but I'm sure doctors are well aware of ways to treat secondary bacterial pneumonia. Just looking at what doctors are saying about Zinc, it seems like there could be something to it, especially if an individual is Zinc deficient, but it's not at all clear it's anything like a silver bullet. https://www.medicinenet.com/script/main/art.asp?articlekey=228691 https://www.medicinenet.com/script/main/art.asp?articlekey=2... We have no idea what the mechanism of action if for HCQ. My doctor friend tried looking it up and it seemed like there are many possible pathways, many of which are still being researched, that modify immune response. There was one statement that speculated if HCQ could act directly on viral particles by changing pH near a key molecule. My attitude is, great if it works, but we still are very far from knowing that for certain. One thing that I think is worth keeping in mind is that if a medicine kills 1% of the people we give it to, and we give it to a large number of people relatively indiscriminately, it's about as bad as COVID, which kills 1-5% of victims (though as much as 15% for high risk patients).
- addicted44 7y ago
  Any high level official recommending it is a bad thing in itself. The major issue is that there isn't enough evidence there for drug companies to put in money to ramp up supply. Heck, there wasn't enough evidence for Trump, who had just signed a trillion dollar stimulus, to divert a few tens of millions of dollars to ramp up supply. Yet, you are telling a bunch of people who may never be able to make use of it to go buy the existing supply on the market. This existing supply exists because there are people who have actual proven needs of the drug, and as a result now you've also made the drug unavailable for uses where it's actually been proven to work.
- berryjerry 7y ago
  Sorry to say but this sounds like a Darwin award. People always worry about the stupidest in society but if it wasn't one thing it would be another for them. If the danger of something is that stupid people act stupidly then I don't see it as a danger at all. This is why people can sell cure all homeopathic drinks that only succeed in making you relieve your bowels or "cleanse your body" as they would say. In this case the people are doubly stupid because not only do they believe something wrong, but they believe it wrong not from a lie, but because they are interpreting "promising trials" as something already working.
- giardini 7y ago
  nick_kline>"and now my elderly relatives are fixated on getting it(HCQ/CQ)." Do you think Trump and Fox News are your elderly relatives only source of information? Do you think this behavior is limited to your elderly relatives? You can't shake an MD today w/o HCQ/CQ, zinc and ZPAK pills falling out of their pockets. Why is that? Firstly, because it works. Secondly, doctors (and dentists, and everyone who could write prescriptions and wasn't living in Tibet) spread the word of using HCQ/CQ+ZINC+ZPAK as a prophylactic measure among themselves. They wrote prescriptions for themselves and theirs, so much so that for awhile they sucked up all the HCQ/CQ in the supply chain. If you think your "elderly relatives" are "fixated", then you must also think that most MDs are also "fixated".But maybe your "elderly relatives" know something you don't know. Perhaps you're the "fixated" one - fixated on false ideas of how to best judge from social behavior in the heat of possible disaster what most likely works and what does not work. In this situation "doing what the doctors are doing" makes sense. The poor lost soul by the side of the road, waving a red flag and saying "But what about randomized controlled double-blind trials? I must have real science!" is the person that Darwin's theories will leave behind.
xiphias2 7y ago
It was a multi-drug combination therapy without real control arm as far as I saw. Also the 95% confidence intervals were overlapping, and the probablity of the high dosage being more lethal is not published.
- brokensegue 7y ago
  So you think they were mistaken to stop the trial? Or what?
  - xiphias2 7y ago
    No, when we are talking about taking away human lives, even with a little bit of data it’s immoral to continue a human trial. The problem is with the binary reporting that doesn’t get into the nuances of the data that we’re getting. People are getting confused and disappointed, because it looks like there’s a new miracle cure every day. And at the end cynical people are wright when it comes to this kind of binary reporting. And then cynism can lead to bad decisions.
rdtsc 7y ago
> Meanwhile they touched several times on the fact that Trump touted the drug. I did notice that. There were articles and some research before and everyone seemed interested and noticed as soon as he mentioned it the majority opinion almost immediately switched to "it's dangerous", "let's avoid it", "it probably won't work" while all the other alternatives seem to be still "interesting" and "worth studying" etc.
- outworlder 7y ago
  > I did notice that. There were articles and some research before and everyone seemed interested and noticed as soon as he mentioned it the majority opinion almost immediately switched to "it's dangerous", "let's avoid it", "it probably won't work" while all the other alternatives seem to be still "interesting" and "worth studying" etc. The fact that a politician is pushing an (yet) unproven drug has to be viewed with skepticism. The flip side is that it caused a cascade of reactions from other governments trying to control the drug's supply. They may have reasoned that a world leader has information they do not. And other governments (see this article) started pushing it as a treatment too. Additionally, now people are pushing the drug as a political issue. By people, I mean the average joe. This is damaging. Regardless, science is doing its thing. Trials are ongoing, as this article shows. But politicians should refrain from making baseless statements about subjects they know zero about.
  - dmix 7y ago
    Notably on Feb 4th China announced their researchers were recommending testing chloroquine, about a month and a half(?) before Trump mentioned it: http://www.whiov.ac.cn/kyjz_105338/202002/t20200204_5497136.html?from=groupmessage http://www.whiov.ac.cn/kyjz_105338/202002/t20200204_5497136.... https://www.nytimes.com/2020/02/06/health/coronavirus-treatments.html https://www.nytimes.com/2020/02/06/health/coronavirus-treatm... https://www.nature.com/articles/s41422-020-0282-0 https://www.nature.com/articles/s41422-020-0282-0 This was the original study which I believe influenced the French study and Dr. Zelenko (who seemed to be the nexus to Trump). The UK banned export of CQ around Feb 26th (I believe the first country to do so): https://ihsmarkit.com/research-analysis/uk-bans-parallel-export-of-two-covid19-treatment-candidates.html https://ihsmarkit.com/research-analysis/uk-bans-parallel-exp... From Google's custom date searches is looks like Trump first mentioned it in a press conference on March 19th: https://twitter.com/cspan/status/1240672025989001221 https://twitter.com/cspan/status/1240672025989001221

hinkley 7y ago

When this clusterfuck first started revealing itself, the forsythia plants in my town had just started flowering. Every time this chloroquine stuff comes up I just hear Jude Law's character from Contagion in my head saying "forsythia" over and over again in different sentence fragments. Unfortunately the SEC isn't going to send men to arrest anybody this time.

klenwell 7y ago
I had the same thought. Here's the clip from Contagion where Jude Law's character, an internet crank, promotes it on national television: https://www.youtube.com/watch?v=CHZ8wx6J36Q https://www.youtube.com/watch?v=CHZ8wx6J36Q
- scared2 7y ago
  Super interesting. It seems that everything is premeditated.
- andy_ppp 7y ago
  Man I really need to watch Contagion then...
  - ornornor 7y ago
    It’s interesting watching it now. I watched it last month and it felt like it was a documentary for what hasn’t happened yet in this epidemics.
    - libria 7y ago
      1 year ago, I'd have thought this movie was typical Hollywood hyperbole. Watching it recently, the scene where Sanjay Gupta is facilitating an interview about the virus was like deja vu. He was literally on TV doing the same thing recently, but for real this time.
    - calyth2018 7y ago
      The only problem is that the vaccine scene won't play out that way in real life. Otherwise Contagion is actually quite accurate.

bearcobra 7y ago

COVID-19 is obviously very scary and I fully understand why we'd want to lessen some restrictions to allow novel treatments to be tried. But as bad as things are, I think people underestimate how much worse they could be if aren't careful when easing those restrictions. There seems to be a mentality that people are going to die anyway so we should be trying anything. That seems to underestimate the potential to make things worse, not just in terms of deaths but also in terms of quality of life for patients.

dionian 7y ago
This is why FDA is not recommending it as a treatment for everyone, only off-label.
- 0xff00ffee 7y ago
  Here's some clarification I googled because I was a little confused by your comment: TL;DR - The FDA only approved it for emergency investigation, not treatment. (as of 2020-03-31): https://www.forbes.com/sites/rachelsandler/2020/03/30/fda-approves-anti-malarial-drugs-chloroquine-and-hydroxychloroquine-for-emergency-coronavirus-treatment/#3d0c01045e5d https://www.forbes.com/sites/rachelsandler/2020/03/30/fda-ap...

ph0rque 7y ago

It irks me to see chloroquine and hydroxychloroquine being used interchangeably in the media. This study used chloroquine. Trump touted hydroxychloroquine. "Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro" https://www.nature.com/articles/s41421-020-0156-0 https://www.nature.com/articles/s41421-020-0156-0

Cantbekhan 7y ago
https://xkcd.com/1217/ https://xkcd.com/1217/
mattkrause 7y ago
This particular article is not bad on that front. For example: "The similar drugs chloroquine and hydroxychloroquine have been pushed by Trump as a possible partial solution to the pandemic..." [Folks, the point is not about Trump here. The point is that the article's author clearly knows that CQ and HCQ are separate but related drugs].
- Florin_Andrei 7y ago
  > pushed by Trump Ah, yes, Trump, the world's leading expert in antiviral medicine. Stop politicizing this issue. Stop feeding the trolls and the demagogues. Let science find things out.
  - mattkrause 7y ago
    That's a verbatim quote from the article, and the point I was trying to make was that the article doesn't conflate them. It says that the drugs are similar (which they are, both chemically and pharmacologically) and have both received some hype. As for "politicizing the issue"...I'm a research scientist (and one who sometimes works with immunologists!). The data on CQ/HCQ make it look useless to me. The good trials show garbage effects and only the garbage "trials" seem to show any results. If you think insisting on careful analysis of data is political...good luck to you.
7y ago

jonplackett 7y ago

This is this the more toxic variant though right? It’s meant to be hydroychloroquine

simtel20 7y ago
Here in Brazil, for whatever reason, the president has been talking up chloroquine, while Trumps talking point is hydroxychloroquine. I don't know how people who have no medical training or experience who are actively trying to undermine their advisors with such experience determine which of these medicines they're going to place their bets on, but given the lack of good results in either, it seems like either bet is as bad as the other.
- goldcd 7y ago
  Like Pepsi and Coke?
  - jcrubino 7y ago
    Like Coke and Diet Coke and Coke Zero
- merpnderp 7y ago
  China had more luck treating COVID with chloroquine phosphate (which is more toxic), but hydrochloroquine sulfate is more available in the US.
  - addicted44 7y ago
    COVID-19 kills anywhere between 0.7-4% of the people it infects. (Some countries like Italy saw a much higher mortality rate, nearing 15% in Italy, I believe, but that was due to the breakdown of the overwhelmed health services). How would one even tell if any of the chloroquinine derivatives have been effective without a systematic study when 96 out of 100 people (at worst) would have recovered anyways? That's another thing that makes the 20 person French study which kicked off all this so much more ridiculous. There was a 44% chance that they would have all recovered without any intervention. But it was probably higher for this group since they did have intervention, and they clearly had a high level of medical assistance.

Carpetsmoker 7y ago

Also interesting read on some more background of the drug: https://blogs.sciencemag.org/pipeline/archives/2020/03/20/chloroquine-past-and-present https://blogs.sciencemag.org/pipeline/archives/2020/03/20/ch...

tannerbrockwell 7y ago

I wonder what happened with the WHO study: "20,000 healthcare workers [will receive] #chloroquine [and] will be tested daily as currently used in the treatment of rheumatoid arthritis for three months or until they are diagnosed with COVID-19." https://www.who.int/blueprint/priority-diseases/key-action/RD-Blueprint-expert-group-on-CQ-call-Mar-13-2020.pdf https://www.who.int/blueprint/priority-diseases/key-action/R...

sdenton4 7y ago
Maybe it will be discontinued, now that the loudest promoter of hydrochloroquine has decided to pull their WHO funding... (The city is on fire! Those hacks at the fire department failed to predict the earthquake! Fire them all!)

Mc_Big_G 7y ago

Fake news. Trump is never wrong /s

tgafpc2 7y ago

Arrhythmia is a well know complication and contraindication of Chloroquine. This should have been identified by the doctors prescribing it and NOT PRESCRIBED IT for at risk patients.

HillRat 7y ago
Unfortunately, COVID may also be associated with hypokalemia, so even patients without comorbidities could be at risk for TdP. HCQ may have therapeutic or prophylactic benefits, but it’s definitely not without serious risks.

DoreenMichele 7y ago

I'm going to note this: The body is the landscape where this battle gets fought. "Nuke it from orbit. It's the only way to be sure." is a treatment policy that should be expected to result in some patients dying. Trump has been vociferous on the drugs’ potential benefits, but among those to contradict his views are his own top expert Anthony Fauci Edit: I stand corrected. The above still horrifies me. I've edited out the inaccurate framing. It's absolutely not intended to make replies to me look dumb. Quite the contrary. This comment has been extensively edited. Hopefully, this is the least worst handling of blurting something out that expresses my concerns badly.

pdonis 7y ago
> this is being tested not because medical professionals think it's a good idea, but because the US president has been loudly promoting it The article is describing a trial in Brazil, not the US. Also, the trial used chloroquine, not hydroxychloroquine. They're not the same.
- 12elephant 7y ago
  Furthermore, the studies on chloroquine started at least a month before the US president ever mentioned hydroxycholoroquine in mid March. E.g. this one from early Feb: https://www.nature.com/articles/s41422-020-0282-0 https://www.nature.com/articles/s41422-020-0282-0 So the research is not only being conducted because of the US president's promotion.

rurban 7y ago

Horrible article. Now what was the problem? CQ or HCQ? Major difference in those two.

stevev 7y ago

I think a high dose of any reactive medication or drug is deadly.

samatman 7y ago
This is a meaningless statement. For starters, to call a compound "reactive" means it's eager to participate in chemical reactions. I'm unable to discern what you were trying to say, but I'm betting it isn't that. To continue, yes, at the limit, a sufficient dose of anything will kill you. The difference between the therapeutic dose and the lethal dose is referred to as the therapeutic index: wide is good, narrow is dangerous. (hydroxy)chloroquine has a fairly narrow therapeutic index at the doses being tested for acute COVID-19 intervention. That's not a property you want in a medicine. It would have to be that much more effective to make up for the risk it poses to the patient.
ska 7y ago
Most everything has an LD50 value but that often doesn't make any practical difference. You can construct scenarios where LD50 of water is relevant, say, but it isn't easy to see them in practice I imagine.

martingoodson 7y ago

This title is misleading. They didn't halt the trial, they halted one treatment arm (the arm with a very high dose). They continued with the 'low' dose (2.7g - about the same dose as used to treat malaria). The high dose was over 4x more of the drug, at 12g.

post_below 7y ago
I haven't looked farther than the linked article, but assuming their reporting is accurate: > However, higher dose use of chloroquine (600 milligrams as opposed to 450 milligrams) was stopped after just six days, after 11 of patients who were given the greater dose died. To me that reads as an increase of about 1.35x rather than 4x.
- bagacrap 7y ago
  600 mg chloroquine twice daily for 10 days or total dose 12g 450 mg for 5 days, twice daily only on the first day, or total dose 2.7 g
  - post_below 7y ago
    That 600mg part of the study ended at 6 days. The potential total dose in a future that didn't happen seems irrelevant.

droithomme 7y ago

They were giving 1.2 grams a day to the patients that died. That is significantly higher than what is known to be a safe dose. CQ is also not indicated for anyone with underlying heart conditions. Since COVID-19 is known to cause heart damage as well as lung damage in the late stage of the disease using these drugs in the late stage of the disease has built in problems. The article doesn't mention anyone in the lower dose group dying of heart problems, though heart attacks and related problems are things that are known to happen to people with COVID-19. The lower dose study is continuing and was not halted. Presumably there will be a subsequent study published with those results. I agree that it is a bad idea to be taking 1.2 grams a day of CQ. During the century of widespread CQ use the fatality rate due to side effects was certainly no where near what they managed to obtain by overdosing patients in this reckless study.

giardini 7y ago

The researchers gave whopping doses of chloroquine to both groups: (a) high dose chloroquine (600 mg chloroquine twice daily for 10 days or total dose 12g); (b) low dose chloroquine (450 mg for 5 days, twice daily only on the first day, or total dose 2.7 g) In addition, all patients received ceftriaxone and azithromycin. So group (a) got 1200 mg chloroquine the first day and group (b) got 900 mg chloroquine the first day. No wonder they had irregular heart rates! Luckily a review board stopped group (a) treatment before they killed all the patients. In contrast, the regimen for Covid-19 _successfully_ used by Dr. Zev Zelenko on ~700 patients is: 1. Hydroxychloroquine 200mg twice a day for 5 days, 2. Azithromycin 500 mg once a day for 5 days, 3. Zinc sulfate 220 mg once a day for 5 days. https://www.freerepublic.com/focus/f-news/3829492/posts https://www.freerepublic.com/focus/f-news/3829492/posts The zinc sulfate is _important_ because it raises the blood level of zinc (Zn++ ion). Chloroquine is a zinc Zn++ "ionophore" which marshals Zn++ across the cell's outer wall into the cytoplasm where the Zn++ can halt viral replication. "Chloroquine Is a Zinc Ionophore": https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4182877/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4182877/ (PDF) https://journals.plos.org/plosone/article/file?id=10.1371/jo.. https://journals.plos.org/plosone/article/file?id=10.1371/jo.... Some researchers seem to be missing the point that chloroquine and its analogs may play a different role here than in malaria, acting not directly against covid-19 but as a facilitator for Zn++, which then halts covid-19 replication. Zelenko's use of an antibiotic(azithromycin = Z-Pak) is a prophylaxis against potential secondary bacterial infection; the antibiotic would not likely play a role against the viral infection directly. Once again we see that randomized, double-blinded clinical trials can be more deadly and less informative than ad-hoc studies performed on the battlefield of medicine.

cycrutchfield 7y ago
> In contrast, the regimen for Covid-19 _successfully_ used by Dr. Zev Zelenko on ~700 patients is: For all we know, it was a successful placebo. Anecdotal evidence does not constitute scientific fact.
- 12elephant 7y ago
  A single piece of anecdotal evidence does not constitute scientific fact. ~700 pieces of anecdotal evidence is a study.

the_mitsuhiko 7y ago

Austria stopped all uses of chloroquine/hydroxychloroquine for covid-19 a few weeks back citing bad outcomes and from what I can tell it's not the only country. I feel like the only reason trials are kept alive are the popularity in the US.

shadowprofile77 7y ago

To be clear, because the title makes it ambiguous, 11 patients died because of the treatment, or 11 paitents died of covid-related/suspected causes despite elevated treatment? It's a crucial distinction. The article doesn't perfectly specify which either. Covid-19 is already becoming known for causing cardiac problems in some patients, so if they were killed by a fatal heart arrhythmia, how to be sure that the medication caused it to be fatal instead of the disease progression itself due to myocarditis or something related combining with said arrhythmia.

lenkite 7y ago

Those dosage numbers are completely OFF the charts. Thats ridiculously high dosage. In India, it's 200mg for treatment of Covid 19. 600mg WILL kill you. I don't even understand who approved that!