Ivermectin for preventing and treating COVID-19

Abstract

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...

Is the antiparasitic drug ivermectin a suitable candidate for the treatment of epilepsy?

“…A recent double‐blind, randomized, placebo‐controlled, adaptive platform trial involving >3000 symptomatic SARS‐CoV‐2–positive adults receiving either placebo or a relatively high dose (.4 mg/kg) of ivermectin once daily for 3 days did not result in a lower incidence of medical admission to a hospital due to progression of COVID‐19 in the ivermectin‐treated patients 117 . Several other randomized clinical trials and recent meta‐analyses showed similar findings 118,119 . Notwithstanding these findings, ivermectin is widely prescribed for COVID‐19 and is often used at high doses that may cause toxicity.…”

“…117 Several other randomized clinical trials and recent meta-analyses showed similar findings. 118,119 Notwithstanding these findings, ivermectin is widely prescribed for COVID-19 and is often used at high doses that may cause toxicity.…”

Evaluating Risk: Benefit Ratio of Fat-Soluble Vitamin Supplementation to SARS-CoV-2-Infected Autoimmune and Cancer Patients: Do Vitamin–Drug Interactions Exist?

“…Given that many of the suggested anti-COVID-19 drug agents are activated/metabolized by CYP3A4, this highlights the importance of studying the drug interactions related to vitamin D [ 202 ]. Ivermectin, for instance, has been suggested to have antiviral effect against COVID-19 and is metabolized via CYP3A4, hence a 2 h delay between the administration of ivermectin and vitamin D has been advised [ 203 ]. Another medication suggested in COVID-19 therapy due its anti-inflammatory effects is colchicine [ 204 ].…”

Pragmatic and open science-based solution to a current problem in the reporting of living systematic reviews

“…Since 2015 Cochrane and other journal publishers have been exploring the publication of LSRs using different updating and publishing approaches 5. Having been involved in the production of several LSRs on COVID-19 for Cochrane, we used an approach adopted by many other author teams, which consists of running searches and screening results on a regular basis and publishing an updated version of the review as new evidence is identified 6 7. However, details of the ongoing surveillance between published LSR updates are not reported, leaving readers in the dark about whether the review is up to date and which new underpinning evidence, for example, relevant new studies, has become available since the last publication.…”