First up is this study from France. It’s another very small one, and all the usual warnings apply because of that. It’s from a team at the University of Paris and Saint-Louis Hospital there, and they evaluated 11 consecutive patients admitted there with the same course of treatment as the Marseilles group first reported (hydroxychloroquine 600mg/day and azithromycin, 500mg the first day and 250 mg/day thereafter).
…One patient died (and two others went on to the ICU) and of the ten remaining, 8 were still positive for the virus by nasal swab on days 5/6 after treatment. One patient had to discontinue therapy on day 4 because of QT prolongation, a known side effect of hydroxychloroquine that can lead to fatal heart arrhythmia.
So while this is a small study and not a perfect match, it provides no evidence to show that the HCQ/AZ combination had any benefit at all.
While we’re on the subject of QT prolongation, there’s this preprint from a medical team at NYU that was also treating patients with the same combination of drugs. In 84 patients, they found notable QT prolongation in about 30% of them, and another 11% were to a level (>500 milliseconds) that put them at a high risk for arrhythmia. This group’s mean age was 63, 74% male. No
But with that in mind, the authors report what looks like a bad interaction in that species between HCQ and metformin. And by “bad”, I mean about 30% mortality. If this translates at all to humans, it could be bad news, because (as mentioned above) diabetics look like a high-risk group and many patients may well have been taking metformin when they present at the hospital.
It’s weird and startling, though, if you haven’t had the opportunity to go back through clinical research (and even patient treatment) and seen how many things looked like they worked and really didn’t. It happens again and again. Alzheimer’s drugs, obesity drugs, cardiovascular drugs, osteoporosis drugs: over and over there have been what looked like positive results that evaporated on closer inspection. After you’ve experienced this a few times, you take the lesson to heart that the only way to be sure about these things is to run sufficiently powered controlled trials. No short cuts, no gut feelings – just data.
Learn More… A Really Bad Clinical Study on COVID-19
Worst of all, there is no evidence from this paper that these two drugs made any difference in the clinical outcomes of these patients. I understand that this was a pilot study and that it will require a much larger trial to determine if hydroxychloroquine has any effect on clinical outcomes, but the hype over this study is unconscionable. This is at best an uncertain result from a very preliminary study with very serious methodological shortcomings that looked only at viral positivity in nasopharyngeal aspirates….
Comparing HydroxyChloroquine Trials
One minor side effect of the pandemic is that perhaps more people will learn about what drug research and clinical trials can really be like.