A Pilot, Randomised, Placebo-Controlled, Double-Blind Trial of a Single Oral Dose of Ivermectin for Post-Exposure Prophylaxis of SARS-CoV-2.

Abstract

Background: The efficacy of a single oral dose of Ivermectin as prophylaxis for SARS-CoV-2 is uncertain. This trial sought to evaluate the effectiveness of a single oral low dose of Ivermectin to prevent SARS-CoV-2 infection or reduce symptoms if infection did occur. Methods: Asymptomatic community-dwelling adults were enrolled in this study within 72 h of close contact with a case of SARS-CoV-2. Participants were randomised, stratified by vaccination status and exposure site, to a single oral 200 µg/kg dose of Ivermectin or placebo. The primary outcome was conversion to a positive polymerase chain reaction (PCR) or rapid antigen test (RAT) for SARS-CoV-2 within 14 days of close contact. Secondary outcomes were restricted to those who met the primary outcome. They included the following: days alive free of symptoms in the 14 (DAFS1-14) and 28 (DAFS1-28) days following intervention and days from close contact until a positive PCR or RAT for SARS-CoV-2. Results: A total of 536 participants registered for this trial. Of these, 86 met inclusion criteria and were randomised. 68 adhered to the trial protocol and were included in the analysis. A total of 11/36 (Ivermectin arm) and 11/32 (placebo arm) met the primary outcome. After controlling for age and prior SARS-CoV-2 infection, the estimate (95% confidence interval (95% CI)) of the effect of Ivermectin (compared to placebo) on the absolute value of the proportion of participants converting to a positive PCR or RAT was -0.051 (-0.26 to 0.16), p = 0.63. After controlling for prior SARS-CoV-2 infection, age, body mass index, hypertension and lung disease, the average treatment effect (Ivermectin versus placebo) on DAFS1-14 was 2.5 days (95%CI 1.1 to 4.5), p = 0.036, and for DAFS1-28, was 2.3 days (95% CI 0.7 to 3.3), p = 0.35. The mean (standard deviation) number of days from close contact until a positive PCR or RAT was 5.0 (4.1) days for the Ivermectin group versus 2.6 (0.8) days for the placebo group. After controlling for age and prior SARS-CoV-2 infection, the average treatment effect (95%CI), Ivermectin versus placebo, on days from close contact until a positive PCR or RAT was 2.3 days (95% CI 1.1 to 3.4), p = 0.033. Conclusions: We did not demonstrate that a single oral low dose of Ivermectin administered to asymptomatic adults within 72 h of close contact with a case of SARS-CoV-2 prevents conversion to a positive PCR or RAT. However, the trial had a small sample size and does not exclude a clinically meaningful effect of Ivermectin on conversion to a positive PCR or RAT. Amongst those who did convert to a positive PCR or RAT, the use of Ivermectin significantly lengthened the time from close contact to conversion and increased the number of days alive free of symptoms following intervention.