Journal des maladies infectieuses et de la thérapie

Abstrait

Ivermectin for Patients with Coronavirus Disease 2019: A Systematic Review and Meta-Analysis of Randomised Controlled Trials with Trial Sequential Analysis

Christopher Jer Wei Low, Ryan Ruiyang Ling, Gabriel Yiqin Tham, Ashwin Subramaniam, Bee Choo Tai, Kiran Shekar, Kollengode Ramanathan

Background: Studies evaluating the effectiveness of ivermectin in reducing time to recovery in patients with COVID-19 have yielded mixed results. We conducted a systematic review and meta-analysis to determine if ivermectin was effective in patients with COVID-19.

Methods: Six databases were searched for Randomised Controlled Trials (RCTs), assessing ivermectin in adults hospitalised with COVID-19 up till December 15th, 2021. Random effects meta-analyses (DerSimonian and Laird) were conducted. The risk of bias was evaluated using the Cochrane Risk-ofBias 2 tool, with certainty of evidence rated using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach. Trial sequential analysis (TSA) was conducted on the reduction in time-to-recovery, as well as mortality.

Results: Twenty-three RCTs (3087 patients, 1601 ivermectin and 1486 control) were included in the meta-analysis; 5 with high risk of bias, 13 with moderate risk and 5 with low risk. Ivermectin reduced overall time-to-recovery (Hedges’ g: -0.65, 95%-CI: -1.04 to -0.27, p=0.0009, low certainty), and inhospital mortality (Risk Ratio [RR]: 0.62, 95%-CI: 0.39-0.99, p=0.046, low certainty). There were no differences in hospital length of stay (Hedges’ g: -0.49, 95%-CI: -1.16 to 0.18, p=0.15, low certainty), or the final proportion of patients with negative SARS-CoV-2 PCR (RR: 1.04, 95%-CI: 0.98-1.10, p=0.18, low certainty). TSA found that the cumulative Z-curve passed the TSA-adjusted boundary for benefit for time to recovery. The cumulative Z-curve did not pass the boundaries for benefit or futility for reduction in mortality.

Conclusion: Our meta-analysis revealed ivermectin may reduce time-to-recovery in patients with COVID-19. However, most RCTs included were limited by risk of bias in the randomisation process, reporting of outcomes and deviations from intended interventions. There was also significant heterogeneity in terms of timing, duration, and dosing of ivermectin. Thus, the apparent benefit seen in this analysis should be interpreted in this context.