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 is not logical, 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, reducing the potential benefit of additional treatments.
Authors have not responded to a request for data.
Angkasekwinai et al., 12 Jun 2022, Double Blind Randomized Controlled Trial, placebo-controlled, Thailand, peer-reviewed, mean age 38.4, 9 authors, study period August 2021 - November 2021, dosage 400μg/kg days 1-3, 400-600µg/kg.
Contact:
nasikarn@gmail.com (corresponding author), pinyo.rat@mahidol.ac.th, methee.cha@mahidol.ac.th, pakpoom.pho@mahidol.ac.th, pornpan.koo@mahidol.ac.th, walaiporn.wan@mahidol.ac.th, visanu.tha@mahidol.ac.th, sorawit.cha@mahidol.ac.th, varalak.sri@mahidol.ac.th, nasikarn.ang@mahidol.ac.th.
Safety and Efficacy of Ivermectin for the Prevention and Treatment of COVID-19: A Double-Blinded Randomized Placebo-Controlled Study
Nasikarn Angkasekwinai, Pinyo Rattanaumpawan, Methee Chayakulkeeree, Pakpoom Phoompoung, Pornpan Koomanachai, Sorawit Chantarasut, Walaiporn Wangchinda, Varalak Srinonprasert, Visanu Thamlikitkul
Antibiotics, doi:10.3390/antibiotics11060796
The safety and efficacy of ivermectin for the prevention and treatment of COVID-19 are still controversial topics. From August to November 2021, we conducted a double-blinded, randomized controlled trial at Siriraj Hospital, Thailand. Eligible participants were adults ≥ 18 years with suspected COVID-19 who underwent a SARS-CoV-2 RT-PCR test. After enrollment, the participants were randomized to receive either ivermectin (400-600 µg/kg/d) or placebo once daily for 3 days. Among 983 participants, 536 (54.5%) with a negative RT-PCR result were enrolled in the prevention study, and 447 (45.5%) with a positive RT-PCR result were enrolled in the treatment study. In the prevention study, the incidence of COVID-19 on Day 14 was similar between the ivermectin and the placebo group (4.7% vs. 5.2%; p = 0.844; ∆ = −0.4%; 95% CI; −4.3-3.5%). In the treatment study, there was no significant difference between the ivermectin and placebo group for any Day 14 treatment outcome: proportion with oxygen desaturation (2.7% vs. 1.9%; p = 0.75), change in WHO score from baseline (1 [−5, 1] vs. 1 [−5, 1]; p = 0.50), and symptom resolution (76% vs. 82.2%; p = 0.13). The ivermectin group had a significantly higher proportion of transient blurred vision (5.6% vs. 0.6%; p < 0.001). Our study failed to demonstrate the efficacy of a 3-day once daily of ivermectin for the prevention and treatment of COVID-19. The given regimen of ivermectin should not be used for either prevention or treatment of COVID-19 in populations with a high rate of COVID-19 vaccination.
Conflicts of Interest: The authors declare no conflict of interest.
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