Data is starting to come out from big trials testing hydroxychloroquine as experimental therapy to fight #covid19. So where are we at on the question of whether it works? It’s not looking good. At all. Here is my @NewsfromScience story. Thread to follow. sciencemag.org/news/2020/06/t…
@NewsfromScience The earliest data on chloroquine (CQ) and hydroxychloroquine (HCQ) came from test tube experiments showing the compounds can keep cells from being infected by #SARSCoV2. But high dose needed and the therapeutic window (the margin between an effective and a toxic dose) is small.
@NewsfromScience So from the beginning CQ and HCQ were seen as long shots by most researchers. For instance, Susanne Herold told me back in March: “Researchers have tried this drug on virus after virus, and it never works out in humans. The dose needed is just too high.” (sciencemag.org/news/2020/03/w…)
@NewsfromScience In fact, HCQ was originally not included in WHO’s trial plans. The expert advisors revised that decision because of the “significant attention” it got, ”prompting the need to examine emerging evidence to inform a decision on its potential role“. (who.int/blueprint/prio…)
@NewsfromScience That "significant attention” was based on case several small studies and case series (some of which had major flaws) plus the hype fuelled by Raoult, Trump and others. And doctors and patients of course were desperate for anything that might help.
@NewsfromScience A meta-analysis of smaller trials recently concluded there was “insufficient and often conflicting evidence on the benefits and harms of using hydroxychloroquine or chloroquine to treat COVID-19.” acpjournals.org/doi/10.7326/M2…
@NewsfromScience So we have all been waiting for data from large, randomised trials that can rule the compounds in or out definitively. Those results are starting to come out and it is not looking good:
@NewsfromScience 1. A post-exposure prophlyaxis study from @boulware_dr published last week: 821 people who had been in contact with a #covid19 patient randomised to placebo or HCQ. 12% on HCQ developed symptoms vs. 14% on placebo. No statistically significant difference. nejm.org/doi/full/10.10…
@NewsfromScience @boulware_dr The study has many limitations. For instance, participants were mailed the drugs, so hard to know if they really took them, cases were diagnosed through symptoms not lab tests, etc. I spoke to @boulware_dr about his trial here: sciencemag.org/news/2020/06/i…
@NewsfromScience @boulware_dr 2. Then the largest study, the UK’s Recovery trial, ended its HCQ arm early. Full data is not out yet, but researchers released the bottom-line: 1542 patients got HCQ, 3132 patients usual care. After 28 days, 25.7% died in HCQ arm and 23.5% in control arm. recoverytrial.net/files/hcq-reco…
@NewsfromScience @boulware_dr This was a really big study with robust results and very high doses of HCQ and the principal investigators are not holding back: "If you, your spouse, your mother gets admitted to hospital and is offered hydroxychloroquine, don’t take it”, @MartinLandray told me.
@NewsfromScience @boulware_dr @MartinLandray 3. Another PEP trial in Barcelona run by @oriolmitja with more than 2000 participants also found that HCQ does not prevent #covid19. There was no significant difference between contacts that took HCQ and contacts that didn’t. Data is not yet published but shared with @WHO etc.
@NewsfromScience @boulware_dr @MartinLandray @oriolmitja @WHO Taken together all this data (gathered in a rush in the middle of a pandemic!) suggests to many researchers that it is time to move on. As @EricTopol told me: "We’d be better off shifting our attention to drugs that might actually work”.
@NewsfromScience @boulware_dr @MartinLandray @oriolmitja @WHO @EricTopol But there are literally hundreds of studies of CQ and HCQ planned or already running: low and high doses; alone and combined with other drugs; in patients with mild or severe disease, health care workers, pregnant women, elderly, HIV+, etc,.. Will they stop?
@NewsfromScience @boulware_dr @MartinLandray @oriolmitja @WHO @EricTopol Will be interesting to watch @WHO make a decision on Solidarity trial which is quite similar to the Recovery trial. They may well decide to end HCQ arm soon and that could be a signal for many researchers to move on too. We will see.
@NewsfromScience @boulware_dr @MartinLandray @oriolmitja @WHO @EricTopol One important exception are Pre-exposure prophylaxis PrEP trials (giving the drug prophylactically to health-care workers etc). Most researchers agree that those should go ahead, since the drug might still be able to prevent disease given that early (and there is little else).
@NewsfromScience @boulware_dr @MartinLandray @oriolmitja @WHO @EricTopol Of course, the uproar around HCQ, reports on the retracted Lancet paper etc. may make it difficult even for those trials to go ahead. “I just think these trials have been really badly damaged and some of them may never restart”, says Nick White, who is running one of them.
@NewsfromScience @boulware_dr @MartinLandray @oriolmitja @WHO @EricTopol For now, it looks like the #covid19 chapter in the tumultuous saga of chloroquine and hydroxychloroquine may be nearing its (scientific) end.
Though, of course: if this drug has proven anything in its history it’s that it is always good for a late comeback...
Though, of course: if this drug has proven anything in its history it’s that it is always good for a late comeback...
