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risk of case with high viral load, 96.0% lower, RR 0.04, p < 0.001, treatment 4 of 200 (2.0%), control 99 of 199 (49.7%), NNT 2.1.
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risk of case, 71.6% lower, RR 0.28, p < 0.001, treatment 30 of 200 (15.0%), control 105 of 199 (52.8%), NNT 2.6, primary outcome.
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| Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates |
Introduction
Ivermectin (IVM) is currently used to treat several parasitic diseases and has a proven safety profile over many decades of exposure. It is one of the several drugs explored for its potential therapeutic and preventive role against SARS-CoV-2 infection. Previous studies had reported its antiviral effects on both RNA and DNA viruses. Caly et al. demonstrated that a single dose of IVM could control the in vitro replication of SARS-CoV-2. Several mechanisms of action have been suggested for its effect on SARS-CoV-2. Those mechanisms could lead to an efficient SARS-CoV-2 prevention, independently of virus mutations. Post-exposure prophylaxis (PEP) is a method of preventing SARS-CoV-2 infection after a known exposure to the virus that may limit the spread of infection.
Method
The SAIVE Trial (NCT05305560) is a randomized, double blind, multicenter, parallel group, placebo-controlled clinical trial, assessing the efficacy and safety of ivermectin in a post-exposure population, conducted in 11 clinical sites in Bulgaria between March and Oct. 2022. The primary objective of the SAIVE trial was to evaluate the efficacy of a continuous administration of oral ivermectin as post-exposure prophylaxis against SARS-CoV-2 infection in confirmed contact cases. Additionally, this study would further reinforce the safety of continuous exposure to ivermectin, as evaluated in a previous phase 1 study (NCT04632706). Out of 400 enrolled, 399 participants were randomized in a 1/1 ratio to ivermectin or matching placebo. Main inclusion criteria was confirmed contact within 5 days with a positive COVID-19 case (assessed by RT-PCR). Primary endpoint was the proportion of confirmed infections between groups from baseline to day 28.
Conclusion
This study demonstrated highly statistically significant evidence in a large, randomized, double-blind, placebo-controlled study that daily oral treatment with ivermectin reduced the risk of infection following exposure to SARS-CoV-2. Ivermectin was also shown to be safe in doses and duration higher than currently used in approved indications.
Discussion
Ivermectin demonstrated a significant efficacy in preventing COVID-19 infection in a post exposure setting as compared to placebo group. The lower viral loads observed with ivermectin could potentially indicate a lower risk of disease severity and a lower contagiousness. We can hypothesize that ivermectin would be a valuable tool in the protection of at-risk populations, in addition to vaccination. Efficacy of ivermectin administration was similar regardless of the subvariant during the trial (60% of infections were related to Omicron BA.5 and 40% to BA.1.1) and the significance of results is equivalent to overall RRR on the whole population in both subgroups.
