Study: No evidence of efficacy of hydroxychloroquine in hospitalized patients

It&#x27;s important to interpret these results carefully: &quot;no evidence of efficacy&quot; does <i>not</i> imply evidence of no efficacy, and in fact the uncertainty in this study is quite large. The sample size is small enough that it would be very hard for this study to detect the effect of hydroxychloroquine unless that effect is very, very large.<p>From the abstract:<p>&gt; In the HCQ group, 2.8% of the patients died within 7 days vs 4.6% in the no-HCQ group (3 vs 4 events, RR 0.61, 95% CI 0.13-2.89), and 27.4% and 24.1%, respectively, developed acute respiratory distress syndrome within 7 days (24 vs 23 events, RR 1.14, 95% CI 0.65-2.00).<p>The relative risks and confidence intervals are the important numbers here. For example, the relative risk for death is 0.61, meaning the observed risk of death was lower for patients treated with hydroxychloroquine -- but the confidence interval is 0.13 to 2.89, meaning the data is consistent with anything from the risk being much smaller to the risk being much <i>larger</i>. Since there were only 3 deaths in the treatment group and 4 deaths in the control group, it&#x27;s very hard to draw precise conclusions about death rates.<p>I think we can interpret this result to mean that hydroxychloroquine doesn&#x27;t have a miraculously large effect, but the evidence is weak. Other commenters are correct that large randomized trials will be more definitive.<p>(disclaimer: I am a statistician, not a doctor)

Personally I&#x27;m witholding judgment until the results of the PATCH trial (<a href="https:&#x2F;&#x2F;clinicaltrials.gov&#x2F;ct2&#x2F;show&#x2F;NCT04329923" rel="nofollow">https:&#x2F;&#x2F;clinicaltrials.gov&#x2F;ct2&#x2F;show&#x2F;NCT04329923</a>) arrive, as it&#x27;ll finally give us some decent statistical power, and be a full, double-blind RCT. It also has multiple study arms (health-care worker prophylaxis, home-quarantined early stage, hospitalized later-stage), so if it turns out that HCQ is effective but that by the time patients are hospitalized it&#x27;s too late, as some are now suggesting, we should finally know with some degree of certainty.

Given that I need hydroxychloroquine to treat my rheumatoid arthritis, I&#x27;d like this hypothesis to be either proven or disproven as rapidly and as unambiguously as possible.

This whole debate is insane to me -- some people that so-called &quot;experts&quot; don&#x27;t like mentioned HCQ as a possible treatment for coronavirus, and we&#x27;ve ended up in some bizarro world where everyone is shouting and fingers are being pointed over something that really shouldn&#x27;t be controversial or perceived as some sinister plot to destroy clever society.<p>1. HCQ has been used for many decades<p>2. The side effects are generally known<p>3. It may have a positive impact on COVID-19, and it may not.<p>4. Nobody is suggesting long term high doses for anyone, COVID patients or otherwise.<p>5. If people are severe patients of COVID-19, this should certainly be tried as a treatment as long as the patient (or immediate family) is briefed on the potential side effects. The alternative, potential death, makes this a worthy discussion for a doctor&#x2F;patient to have, with families being allowed to err on the side of right-to-try. HCQ is cheap, available, and has been used for decades.<p>The fact that &quot;no evidence HCQ works!!&quot; has 200 points of upvotes and counting <i>when the sample size for this study is 181 patients only</i> just shows how high the temperature has become.<p>Everyone just calm down. As capnrefsmmat has eloquently pointed out, &quot;absence of evidence&quot; does not mean &quot;evidence of absence&quot;.<p>If you enjoy the thrill of debates for debates sake, here are other potential topics for you: Whether masks are effective, condoms, seatbelts, helmets, or even parachutes[0]<i>:<p>[0]<a href="https:&#x2F;&#x2F;www.ncbi.nlm.nih.gov&#x2F;pmc&#x2F;articles&#x2F;PMC300808&#x2F;" rel="nofollow">https:&#x2F;&#x2F;www.ncbi.nlm.nih.gov&#x2F;pmc&#x2F;articles&#x2F;PMC300808&#x2F;</a><p></i>Favourite part:<p><i>Results</i> We were unable to identify any randomised controlled trials of parachute intervention.<p><i>Conclusions</i> As with many interventions intended to prevent ill health, the effectiveness of parachutes has not been subjected to rigorous evaluation by using randomised controlled trials. Advocates of evidence based medicine have criticised the adoption of interventions evaluated by using only observational data. We think that everyone might benefit if the most radical protagonists of evidence based medicine organised and participated in a double blind, randomised, placebo controlled, crossover trial of the parachute.

This study is specifically about patients sick enough to be put on oxygen. The top ranked comments don&#x27;t seem to address that detail.<p>Some thoughts:<p>My understanding is this is a powerful alkaloid. My experience has been that similar compounds can help combat inflammation. They also can work to help kill infection at times.<p>By the time people with Covid19 need oxygen, inflammation doesn&#x27;t seem to be the primary problem. So I wouldn&#x27;t think it would be particularly helpful at that point.<p>Ventilators get prescribed in part on the assumption that inflammation in the lungs is a major impediment to getting sufficient oxygen. Ventilators are failing at a shockingly high rate, with a death rate up around 80% or so. Some doctors are moving away from ventilators because the death rate is so high.<p>I spoke recently with a researcher who suggested impaired vasodilation was a possible explanation for the reports of low oxygen combined with a surprising lack of pneumonia and inflammation in some cases and that makes a lot of sense to me. The mechanism causing low oxygen does not appear to be the obvious answer of &quot;lung inflammation and pneumonia.&quot;<p>That doesn&#x27;t mean this drug can&#x27;t play a meaningful role at some stage. It mostly means it&#x27;s not the magic bullet solution for advanced cases that they were hoping for.<p>This in no way surprises me because the things it actually treats do not appear to be the cause of low oxygen in advanced covid19 cases.

Given the study&#x27;s small sample size, it seems the only way it would have produced a conclusive result is if the effect size was huge (i.e. miracle cure). The study found some evidence of efficacy, but it was not significant given the sample size.<p>A better headline would say something like: &quot;study finds that HCQ is not a miracle cure for already-hospitalized covid-19 patients&quot;.

This trial wasn&#x27;t randomized, but a quasi randomized trial for HCQ whose preprint was leaked is here:<a href="https:&#x2F;&#x2F;www.dropbox.com&#x2F;s&#x2F;8b2govfsa6n0xbq&#x2F;NEJM_Clinical%20Outcomes%20of%20Hydroxychlorquine%20in%20Patients%20with%20COVID19.pdf.pdf.pdf.pdf?dl=0" rel="nofollow">https:&#x2F;&#x2F;www.dropbox.com&#x2F;s&#x2F;8b2govfsa6n0xbq&#x2F;NEJM_Clinical%20Ou...</a> Study indicates that one adverse effect of HCQ (on top of not improving patient outcomes) is increased ventilator times.

Lots of conflicting research happening[1], until we get multiple controlled trials we won&#x27;t really know. Here&#x27;s one that shows improvements.<p>[1] French ~50 patient study that tried Control, Hydroxychloroquine, and Hydroxychloroquine + Azithromycin combo: <a href="https:&#x2F;&#x2F;www.mediterranee-infection.com&#x2F;hydroxychloroquine-and-azithromycin-as-a-treatment-of-covid-19&#x2F;" rel="nofollow">https:&#x2F;&#x2F;www.mediterranee-infection.com&#x2F;hydroxychloroquine-an...</a>

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

It was observed that between 7% and 28% of hospitalized have acute myocardial injury [1-4]. When one looks at Epocrates (database for drugs which is why I&#x27;m not linking anything here) the severe adverse reactions of hydroxycholoroquine include QT prolongation, cardiomyopathy, and torsade de pointes. Just to define some things here, QT prolongation is the time from your Q wave to your T wave, or the start of an electrical depolarization on your cardiac ventricles to repolarizations. QT elongation usually leads to cardiac arrest. Torsade de pointes is a syndrome where your cardiac ventricles beat so quickly that your heart paradoxically cannot fill up with blood potentially, and usually, leading to sudden cardiac death.<p>Giving someone who has had essentially a heart attack (by definition COVID patients have elevated troponin which is the marker we use to assess if one has had a heart attack) is probably a bad idea so my question is: why would we celebrate a drug that has massive cardiac adverse effects as a side effect? Don&#x27;t get me wrong I understand that there are drugs that are even worse. Cyclosporine is the first line immunosuppresant for kidney transplant. Do you know what one of the most common adverse effects of cyclosporine is? Kidney failure. But we don&#x27;t know what is causing the kidney failure in a kidney transplant (rejection vs adverse effect) so we have to biopsy. Kidney biopsy is a very invasive procedure, FYI. My point is, maybe waiting for double blind placebo research here is the best case. Also, I made this exact same point on here a month ago and people told that they would take my dose if it came to that and at this point I will say go ahead.<p>[1] <a href="https:&#x2F;&#x2F;www.ncbi.nlm.nih.gov&#x2F;pubmed&#x2F;32169400" rel="nofollow">https:&#x2F;&#x2F;www.ncbi.nlm.nih.gov&#x2F;pubmed&#x2F;32169400</a><p>[2] <a href="https:&#x2F;&#x2F;www.nejm.org&#x2F;doi&#x2F;full&#x2F;10.1056&#x2F;NEJMoa2004500" rel="nofollow">https:&#x2F;&#x2F;www.nejm.org&#x2F;doi&#x2F;full&#x2F;10.1056&#x2F;NEJMoa2004500</a> [3] <a href="https:&#x2F;&#x2F;www.ahajournals.org&#x2F;doi&#x2F;10.1161&#x2F;CIRCULATIONAHA.120.046941" rel="nofollow">https:&#x2F;&#x2F;www.ahajournals.org&#x2F;doi&#x2F;10.1161&#x2F;CIRCULATIONAHA.120.0...</a> [4] <a href="https:&#x2F;&#x2F;jamanetwork.com&#x2F;journals&#x2F;jamacardiology&#x2F;fullarticle&#x2F;2763524" rel="nofollow">https:&#x2F;&#x2F;jamanetwork.com&#x2F;journals&#x2F;jamacardiology&#x2F;fullarticle&#x2F;...</a>

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

I think it&#x27;s too bad that this drug has been so politicized. It&#x27;s really unfortunate that its two original and most prominent champions are people that are so disliked. So many people spoke up (maybe prematurely) against it in a knee-jerk reaction to its advocates. Now many act as if they&#x27;re more concerned about being right to ridicule the claims all along, than they are about whether the drug is actually helpful in fighting COVID-19. Which, for the rest of us without a stake in their stupid political feuds, is all that matters. And because of this idiotic battle of the egos we could be passing on something useful.<p>So here we all are, hanging by the edge of our seats, waiting for definitive proof that <i>HCQ does not help in fighting COVID-19</i> and we keep getting these half-assed reports, seemingly more aimed at pushing a narrative than to present (or eliminate) an option in a fight.<p>One of the latest examples is the account of Rita Wilson (wife of Tom Hanks) who survived what seems like a difficult case of COVID-19 and shared her experience with the media: she felt very tired, extremely achy, uncomfortable, didn&#x27;t want to be touched, on the ninth day her fever climbed up to 102 and she had chills like she&#x27;d &quot;never had before&quot; (her words), she lost her sense of taste and smell. Then she was given chloroquine, her fever broke (it&#x27;s not clear how long after). She goes on to warn against the &quot;extreme&quot; (her word) side-effects she attributes to chloroquine: she was completely nauseous, she had vertigo, she could not walk and her muscles felt very weak. She then concludes that although her fever broke after been given chloroquine, she doesn&#x27;t know if it helped or if it was just time, which is fair. What do you imagine the headline for that story should be? Well, to save you the trouble, most read like this <i>Rita Wilson warns against &quot;extreme&quot; side-effects of chloroquine</i>.<p>Are HCQ&#x2F;CQ effective? We&#x27;re still sitting here like idiots not knowing. If they are, should they be taken carelessly? Definitely not, we already got that, thanks, but <i>that is not the point</i>. We can&#x27;t afford to have an &quot;all or nothing&quot; mindset with these drugs as we did with masks. Simply proclaiming that HCQ is useless because it is shown not to reduce viral load is just the best way to pass on some other ways it might be helping. If it is shown to have other palliative effects that actually help patients in their fight, such as reducing inflammation or helping cope with high fever long enough for your immune system to do the job, it&#x27;s not <i>nothing</i>. It&#x27;s information. It&#x27;s an option.

It&#x27;s important to note that this study did not evaluate or note that Hydroxychloroquine had no effect on all people in all situations with COVID-19.<p>This was a targeted study looking at a specific circumstance. The situation was &quot;all adults in 4 French hospitals with documented SARS-CoV-2 pneumonia and requiring oxygen ≥ 2 L&#x2F;min&quot;<p>So, adults who were not on oxygen are not included in the study. How does it pertain to them? That&#x27;s not covered by this.<p>It reads like it&#x27;s saying people who are in bad shape and on ventilators did not have a positive impact by Hydroxychloroquine.<p>This still leaves open questions like, can the use of Hydroxychloroquine lower the rate of needing to get on a ventilator.<p>I look forward to someone reproducing this study and looking into the other areas.

&quot;collected data to <i>emulate</i> a target trial&quot; I take it this means it&#x27;s not an actual clinical trial, just a virtual trial? What&#x27;s the point? Of all the people that died, none were saved by the drug. Sounds like an insurance ad.

The study is way underpowered (too small a sample). Based on the raw numbers, the HCQ group had less deaths and less ICU admissions, but the numbers we&#x27;re talking about are 3 vs. 4 deaths and 16 vs. 21 ICU admissions (group sizes were different).<p>These numbers simply aren&#x27;t enough to make a determination one way or the other. On mortality, the 95% confidence interval allows for a range of HCQ reducing death rates by 87% up to it increasing death rates by 2.9x.

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

A useful compilation of information on HCQ and COVID-19:<p><a href="https:&#x2F;&#x2F;docs.google.com&#x2F;document&#x2F;d&#x2F;1O6Cls-Oz2ZAgJuyDbnICEGjMvQPEyM-aaXARUomR9Ww&#x2F;edit" rel="nofollow">https:&#x2F;&#x2F;docs.google.com&#x2F;document&#x2F;d&#x2F;1O6Cls-Oz2ZAgJuyDbnICEGjM...</a>

This study is basically garbage. It applies to people who&#x27;re so damaged from Covid they need at least 2 liters of oxygen per minute. It studies treatment with pure hydroxychloroquine--no zinc, no azithromycin&#x2F;doxycycline&#x2F;ivermectin. Hydroxychloroquine.<p>Patients who get their treatment from doctors less fraudulent than the authors of this study almost certainly see better outcomes.

When the Covid crisis is over, one of the strangest sub- plots will have been the fracas around Hydroxychloroquine. Starting from medical practitioners worldwide adopting its usage in a ‘cargo cult’ way, mimicking what other doctors were doing, to Raoult’s low- quality study. Then people in Silicon Valley (notably Elon Musk) picking up the idea. Followed by the explosion in the political sphere, from Trump pushing it at the White House podium, to Indian PM Modi reversing an HCQ export ban for Trump, to French PM Macron talking it up.<p>All the while HCQ remained unproven for Covid use, while people trying it got hurt by cardiac side- effects (and one couple in a prominent incident mistakenly took different chemicals with a similar name), and patients with other conditions ran out of HCQ due to shortages.<p>Maybe HCQ will be part of the standard of care for Covid- 19 in the future, but it’s seeming less and less likely. Meanwhile it’s definitely not a miracle cure, so the frenzied advocacy and adoption of this medicine will turn out to have been a bizarre story.<p>(I wrote this up here <a href="https:&#x2F;&#x2F;twitter.com&#x2F;firasd&#x2F;status&#x2F;1250125344469708801" rel="nofollow">https:&#x2F;&#x2F;twitter.com&#x2F;firasd&#x2F;status&#x2F;1250125344469708801</a>)

I don’t understand who gets to decide and how, which of these people receive &#x2F; don’t receive a specific treatment. I’ve always loved medical studies, but now the crisis got me to thinking about the moral decision (playing god?)

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

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

That&#x27;s because it&#x27;s not hydroxychloroquine that helps them. It&#x27;s Zinc. It just allows for much better absorption of the Zinc. Same can be achieved by combining Quercetin and Zinc.

I know this study doesn’t put anything to bed, but one has to understand that the basis for the HCQ and CQ (+&#x2F;- zinc) thing is the same as x kills cancer in vitro. Then, you get a motivated researcher who publishes a single arm study of essentially OK patients claiming zero deaths. Game changer? We’ll see. But I imagine there are hospitals that are already using this as a first line treatment and there’s no positive reviews from the front line.<p>Beyond that, we do have the ability to perform small sample studies (cf. Student) and decide whether we’re headed in the right direction. Are we in a lull in statistics where we can’t even use statistics to guide future research?

See also <a href="https:&#x2F;&#x2F;news.ycombinator.com&#x2F;item?id=22851998" rel="nofollow">https:&#x2F;&#x2F;news.ycombinator.com&#x2F;item?id=22851998</a>

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

full title &quot;No evidence of clinical efficacy of hydroxychloroquine in patients hospitalised for COVID-19 infection and requiring oxygen:...&quot;<p>from the article:<p><i>&quot;We used data collected from routine care of all adults in 4 French hospitals with documented SARS-CoV-2 pneumonia and requiring oxygen ≥ 2 L&#x2F;min to emulate a target trial aimed at assessing the effectiveness of HCQ at 600 mg&#x2F;day...<p>This study included 181 patients with SARS-CoV-2 pneumonia; 84 received HCQ within 48 hours of admission (HCQ group) and 97 did not (no-HCQ group).<p>The median age of patients was 60 years ...&quot;</i><p><i>&quot;...[Patients were from] four French tertiary care centres providing care to patients with COVID-19 pneumonia. Adult patients were eligible in this study if they were aged between 18 years and 80 years, had PCR-confirmed SARS-CoV-2 infection, and required oxygen by mask or nasal prongs (corresponding to a WHO progression score of 5).&quot;</i><p><i>&quot;Among the 181 patients eligible for analysis, 84 received HCQ within 48 hours of admission and 97 did not (although 8 of them did receive HCQ later on).&quot;</i><p>So, first of all, these patients were infected with Covid-19 _days_ prior and now had progressed to pneumonia. The up to two-day delay in the administration of HCQ after admittance to the study is disheartening.<p>I am surprised that, despite the experimentors selecting an elderly, pneumonic, oxygen-dependent cohort in advanced stages of the disease, these patients did as well as they did. Its a credit to the human body.<p>But timing is everything...<p>Once a Covid-19 patient has developed pneumonia, it is too late for hydroxychloroquine to affect the Covid-19 virus&#x27; replication process significantly. The patient&#x27;s body is saturated with the virus.<p>In a patient who has developed pneumonia the disease has progressed to a second phase wherein the virus <i>and other opportunistic pathogens (e.g., bacteria)</i> attack the lungs and other tissue. Antibiotics may help at this point. But it is quite clear that the patients in this study arrived too late to gain any benefit from hydroxychloroquine which, when coupled with zinc sulfate, slows or halts viral replication _early_ in the disease, delays or halts the virus&#x27; progress and allows the body time to develop an immunological response to the virus.<p>The study&#x27;s conclusion states explicitly that &quot; These results ... do not support the use of HCQ in patients hospitalised for a documented SARS-CoV-2 pneumonia.&quot;<p>So, the trick is to treat _early_ with HCQ+zinc sulfate+azithromycin.

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

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

Sample size is far too small.<p>If anything this study shows (albeit with small numbers) that HCQ doesn&#x27;t make things worse.<p>But I have a feeling HCQ will be found to be effective. Big pharma have a lot of $$$ to make from their vaccine though.

There is an obvious pushback on hydroxychloroquine. Not enough money to be made so other &quot;solutions&quot; are preferred. Something that was used for more than 50 years is being tested for safety? What a joke. I&#x27;m sure when vaccines arrive they&#x27;ll be &quot;safe and effective&quot; and used all around the world from day one...

There is an obvious pushback for hydroxychloroquine. Something that was used for more than 50 years should&#x27;ve been widely adopted by now but there is not enough money to be made (and let&#x27;s not forget political issues). I&#x27;m sure when vaccine arrives it&#x27;ll be &quot;safe and effective&quot; and widely used around the world from day one - no questions asked.

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

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

It <i>really</i> bothers me how hard both citizens and officials seem to be wanting Chloroquine to fail all because somebody they didn&#x27;t like endorsed it publicly. Can&#x27;t let him have that win, right? Like children.<p>The original studies that showed promise used combinations of Chloroquine, Azithromycin, and or zinc, and there is a speculated pathway by which these drugs interact to interfere with COVID replication. This study only looked at HCQ.<p>This kind of partisan, childlike pettiness is dangerous to all of us - what if Chloroquine works but we overlooked it because a couple shitty papers told us what we wanted to hear?<p>Was it appropriate to tweet about? Debatable. It is a presidents job to keep his people hopeful when possible, and this drug cocktail was in multiple (admittedly not perfect) papers at the time of the tweet. People need to be more objective when evaluating statements made by the president. That doesn&#x27;t mean you have to like him.

Wow, several HCQ stories on the front page. Means it&#x27;s probably going to be proven effective soon.

Totally out of my depth here. I&#x27;ve been following Dr. Chris Martenson&#x27;s daily covid-19 updates since late January. He is adamant this treatment is only effective in combination with zinc supplements.

While we&#x27;re here,<p>&quot;Traditional Chinese Medicine in the Treatment of Patients Infected with 2019-New Coronavirus (SARS-CoV-2): A Review and Perspective&quot; (<a href="https:&#x2F;&#x2F;www.ncbi.nlm.nih.gov&#x2F;pmc&#x2F;articles&#x2F;PMC7098036&#x2F;" rel="nofollow">https:&#x2F;&#x2F;www.ncbi.nlm.nih.gov&#x2F;pmc&#x2F;articles&#x2F;PMC7098036&#x2F;</a>)<p>Hey, it can&#x27;t hurt and it might help. China has had one of the best recoveries from the pandemic.

What a joke. An emulated trial only in patients already requiring oxygen. How about this <a href="http:&#x2F;&#x2F;covexit.com&#x2F;professor-didier-raoult-releases-the-results-of-a-new-hydroxychloroquine-treatment-study-on-1061-patients&#x2F;" rel="nofollow">http:&#x2F;&#x2F;covexit.com&#x2F;professor-didier-raoult-releases-the-resu...</a><p>I&#x27;m taking the HQZ cocktail at first diagnosis even if I have to doctor shop.

&gt; documented SARS-CoV-2 pneumonia and requiring oxygen ≥ 2 L&#x2F;min to emulate a target trial aimed at assessing the effectiveness of HCQ at 600 mg&#x2F;day<p>Well hydroxychoroquine is only useful before ventilators are needed (it attacks the full lungs) and is actually detrimental - we know that - after by its nature.<p>What kind of bad science is this study where you actually push patients through a known dangerous path to try to prove the non efficiency of a potential treatment.