Ivermectin reduces the risk of death from COVID-19 – a rapid review and meta-analysis in support of the recommendation of the Front Line COVID-19 Critical Care Alliance.
Recently a group of expert critical care physicians, called the Front Line COVID-19 Critical Care Alliance (FLCCC), reviewed the evidence on the effects of ivermectin on SARS-CoV-2 virus and COVID-19 infections.1 They concluded that the evidence on ivermectin “demonstrates a strong signal of therapeutic efficacy” and recommended that ivermectin is adopted globally and systematically for the prophylaxis and treatment of COVID-19.1 Ivermectin is an anti-parasitic medication widely used in low- and middle-income countries to treat parasitic worm infections in adults and children. 1,2 Having been used for decades for this purpose, it is considered extremely safe and effective2,3 and has an increasing list of indications due to its antiviral and anti-inflammatory properties.4 On the WHO’s Model List of Essential Medicines it is retained in the form of a 3 mg tablet.5 For parasitic infections in adults, ivermectin is commonly administered as a single 12 mg oral dose (0.2mg/kg).
Description of studies Fifteen study reports were included, nine of RCTs and six of OCTs. One RCT (Elgazzar 2020) reported findings of a prophylaxis study and a treatment study within the same paper and these were regarded as separate studies. Similarly, one OCT (Carvallo 2020) reported findings of a pilot study and a further multicentre study and these were treated separately. Eleven studies were excluded with reasons (see supplementary file). Five of the included studies involving 2045 participants were of COVID-19 prophylaxis among health care workers and patient contacts; the remaining 13 involving 1835 participants were of COVID19 treatment. Study sample sizes ranged from 24 to 1195 participants and studies were conducted in Argentina (2), Bangladesh (6), Egypt (3) India (1), Iran (2), Pakistan (1), Spain (1), and the USA (1) (Table 1). Fifteen studies were at low or moderate risk of bias and two studies were at high risk of bias. Eight were registered on clinical trial registries; most 4 appeared to be self-funded, undertaken by clinicians working in the field not by dedicated research teams. There were no apparent conflicts of interest.
OCT, observational controlled trial; RCT, randomised controlled trial *Also administered doxycycline. Note: 0.2 mg/kg is equivalent to giving 12 mg and 0.4 mg/kg is equivalent to giving 24 mg for a 60 kg person.
Comparison 1: Ivermectin treatment versus control Analysis 1.1: Death Moderate certainty evidence indicates that ivermectin probably reduces deaths by an average 83% (95% CI, 65% to 92%) compared with no ivermectin treatment (5 RCTs, 1107 participants; RR 0.17, 95% 0.08 to 0.35; risk of death 1.4% versus 8.4% among participants in this analysis).
A second analysis, which includes OCTs can be found in the Appendix at the end of this document. Findings from the latter analysis which included nine studies and 1735 participants are consistent with the above analysis and suggest a probable reduction in deaths of about 69% on average (RR 0.31, 95% CI 0.16 to 0.61; risk of death was 3.9% vs 9.9 %), a slightly more modest effect estimate than the analysis above that includes RCTs only.
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