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upstart writes in with an IRC submission for Bytram:

The Latest Hydroxychloroquine Data, As of April 11:

We have new data on hydroxychloroquine therapy to discuss. The numbers will not clear anything up.

The good news is that the HCQ/sulfasalazine comparison does not show any real differences in adverse events over one-month courses of treatment. I should note that sulfasalazine is not the most side-effect-free medication in the whole pharmacopeia, but it has not been associated with (for example) QT prolongation, which is one of the things you worry about with hydroxychloroquine. The paper concludes that short-term HCQ monotherapy does appear to be safe, but notes that long-term HCQ dosing is indeed tied to increased cardiovascular mortality.

The trouble comes in with the azithromycin combination. Like many antibiotics (although not amoxicillin), AZM is in fact tied to QT prolongation in some patients, so what happens when it's given along with HCQ, which has the same problem?

Worryingly, significant risks are identified for combination users of HCQ+AZM even in the short-term as proposed for COVID19 management, with a 15-20% increased risk of angina/chest pain and heart failure, and a two-fold risk of cardiovascular mortality in the first month of treatment.

That isn't good. I am very glad to hear that the Raoult group has observed no cardiac events in their studies so far, but I wonder how they have managed to be so fortunate, given these numbers.

Update: here is another new preprint from a multinational team lead out of Brazil. It enrolled 81 patients in a trial of high-dose hydroxychloroquine  (600 mg b.i.d. over ten days, total dose 12g) or low-dose (450mg b.i.d. on the first day, qd thereafter for the next four, total dose 2.7g). All patients also received azithromycin and ceftriaxone (a cephalosporin antibiotic). The high-dose patients showed more severe QT prolongation and there a trend toward higher lethality compared to the low dose. The overall fatality rate across both arms of the study was 13.5% (so far), which they say overlaps with the historical fatality rate of patients not receiving hydroxychloroquine. The authors actually had to stop recruiting patients for the high-dose arm of the study due to the cardiovascular events, but they're continuing to enroll people in the low-dose group to look at overall mortality. The paper mentions that HCQ has been mandated as the standard therapy in Brazil, so there is no way to run a non-HCQ control group, though.

Original Submission