Background
Ivermectin, an antiparasitic agent, inhibits the replication of viruses in vitro. The molecular hypothesis of ivermectin's antiviral mode of action suggests an inhibitory effect on severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) replication in early stages of infection. Currently, evidence on ivermectin for prevention of SARS‐CoV‐2 infection and COVID‐19 treatment is conflicting.
Objectives
To assess the efficacy and safety of ivermectin plus standard of care compared to standard of care plus/minus placebo, or any other proven intervention for people with COVID‐19 receiving treatment as inpatients or outpatients, and for prevention of an infection with SARS‐CoV‐2 (postexposure prophylaxis).
Search methods
We searched the Cochrane COVID‐19 Study Register, Web of Science (Emerging Citation Index and Science Citation Index), WHO COVID‐19 Global literature on coronavirus disease, and HTA database weekly to identify completed and ongoing trials without language restrictions to 16 December 2021. Additionally, we included trials with > 1000 participants up to April 2022.
Selection criteria
We included randomized controlled trials (RCTs) comparing ivermectin to standard of care, placebo, or another proven intervention for treatment of people with confirmed COVID‐19 diagnosis, irrespective of disease severity or treatment setting, and for prevention of SARS‐CoV‐2 infection. Co‐interventions had to be the same in both study arms.
For this review update, we reappraised eligible trials for research integrity: only RCTs prospectively registered in a trial registry according to WHO guidelines for clinical trial registration were eligible for inclusion.
Data collection and analysis
We assessed RCTs for bias, using the Cochrane RoB 2 tool. We used GRADE to rate the certainty of evidence for outcomes in the following settings and populations: 1) to treat inpatients with moderate‐to‐severe COVID‐19, 2) to treat outpatients with mild COVID‐19 (outcomes: mortality, clinical worsening or improvement, (serious) adverse events, quality of life, and viral clearance), and 3) to prevent SARS‐CoV‐2 infection (outcomes: SARS‐CoV‐2 infection, development of COVID‐19 symptoms, admission to hospital, mortality, adverse events and quality of life).
Main results
We excluded seven of the 14 trials included in the previous review version; six were not prospectively registered and one was non‐randomized. This updated review includes 11 trials with 3409 participants investigating ivermectin plus standard of care compared to standard of care plus/minus placebo. No trial investigated ivermectin for prevention of infection or compared ivermectin to an intervention with proven efficacy. Five trials treated participants with moderate COVID‐19 (inpatient settings); six treated mild COVID‐19 (outpatient settings). Eight trials were double‐bli...