Low-risk RCT in Thailand with zero mortality, reporting no significant differences with the addition of ivermectin to favipiravir treatment, however the study as reported does not make sense as detailed below.
All participants were suspected of having COVID-19 and authors assigned 536 PCR- at baseline to a “prevention” study where the only outcome tested was cases. However 62% of these patients were already symptomatic at baseline. Since PCR has a high false negative rate in the first few days, patients may already have COVID-19. It doesn’t make sense to study prevention of cases with already symptomatic patients - studying progression and clinical outcomes would make sense, however authors report only case results. The reported time to PCR+ is also not informative because patients were instructed to do an antigen test only if there were new symptoms (followed by a PCR test).
For both “prevention” and treatment, authors note:“All participant without evaluable outcomes and drop-out participant were considered as having a poor outcome”
, and “…assumed all participants who withdraw or do not take the study drug, and those in the prevention study who do not perform the second NP swab, have a poor outcome.”
This makes no sense, participants that recover quickly are more likely to drop out.
Notably, 100% of the 4 ivermectin patients that did not receive the treatment (which may be because they dropped out) were reported as hospitalized (compared to 2% overall). Authors do not report how many patients dropped out or did not have evaluable outcomes.
We are unable to find protocol registration. The study protocol published with the paper unusually uses past tense in a few places, e.g., “290 patients … were needed”
, “The ITT population comprised…”
, and “applied a worst-case scenario”
, as if it was written after the study. The study protocol file metadata indicates creation June 2022 by Pakpoom Phoompoung. The supplementary figure file shows creation April 2022 by Noppasit Musiwiraphat (not a listed author).
Treatment and placebo were labeled as A and B, meaning any indication of treatment assignment results in a total loss of blinding (e.g., if an investigator observes typical treatment side effects, blinding is lost).
The same hospital has an ivermectin vs. HCQ trial which was registered, was due for completion November 2021, but has not reported results [clinicaltrials.gov]
Dyspnea was ~2x more prevalent in the ivermectin group (9.2% vs. 4.7%), suggesting incomparable groups for serious outcomes.
Studies show that favipiravir is effective, limiting the benefit of additional treatments.
Authors have not responded to a request for the data to date.
Angkasekwinai et al., 6/12/2022, Double Blind Randomized Controlled Trial, placebo-controlled, Thailand, South Asia, peer-reviewed, mean age 38.4, 9 authors, study period August 2021 - November 2021, dosage 400μg/kg days 1-3, 400-600µg/kg.
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