OK. I read the high vs. low-dose CQ paper from Amazonas.
I'll start with the money shot and then review the paper. It's got a lot of moving parts and doesn't have the full data it's hoping to report. In the biased subgroup that had EKG pre and post (all got azithro), QT up ~30ms.
I'll start with the money shot and then review the paper. It's got a lot of moving parts and doesn't have the full data it's hoping to report. In the biased subgroup that had EKG pre and post (all got azithro), QT up ~30ms.
Stepping back, it's a complex study. They used Chinese cohorts to "increase" their efficiency and basically ran two compassionate use protocols in parallel, with entry into the compassionate use randomized. They enrolled pending results, and about half had COVID+. The trial
stopped after enrolling 81, but the inferences were drawn on only about 56 patients, with the most important inferences on 25-28 patients. I think the DSMB made a good call--they had clear hits on the QTc and had 2 ventricular arrhythmias in the high dose group, none in low-dose,
in the absence of any compelling data for efficacy and with good biological plausibility for the harm. I think you stop the trial. This suggests that it will be a simple compassionate use protocol hereafter. The discussions about mortality are methodologically meaningless.
So, in summary: (1) Good on them for moving so nimbly and for watching safety so closely when they were forced by social pressures into compassionate use only. (2) high-dose CQ seems like a bad idea; when combined with Azithro it probably leads to a 20-30msec increase in QTc;
(3) there wasn't a similar picture with low-dose CQ, although numbers are tiny. (4) a post-load EKG probably does make sense with CQ/HCQ inside and outside trials, especially if azithromycin is administered concomitantly (4) keep enrolling in trials! We need them desperately.
This is the paper: medrxiv.org/content/10.110… Thanks to @otavio_ranzani for posting the paper.
