Ivermectin for the Treatment of Coronavirus Disease 2019: A Systematic Review and Meta-analysis of Randomized Controlled Trials
Yuani M Roman, Paula Alejandra Burela, Vinay Pasupuleti, Alejandro Piscoya, Jose E Vidal, Adrian V Hernandez
Clinical Infectious Diseases, doi:10.1093/cid/ciab591
Background. We systematically assessed benefits and harms of the use of ivermectin (IVM) in patients with coronavirus disease 2019 . Methods. Published and preprint randomized controlled trials (RCTs) assessing the effects of IVM on adult patients with COVID-19 were searched until 22 March 2021 in 5 engines. Primary outcomes were all-cause mortality rate, length of hospital stay (LOS), and adverse events (AEs). Secondary outcomes included viral clearance and severe AEs (SAEs). The risk of bias (RoB) was evaluated using the Cochrane Risk of Bias 2.0 tool. Inverse variance random effect meta-analyses were performed, with quality of evidence (QoE) evaluated using GRADE methods. Results. Ten RCTs (n = 1173) were included. The controls were the standard of care in 5 RCTs and placebo in 5. COVID-19 disease severity was mild in 8 RCTs, moderate in 1, and mild and moderate in 1. IVM did not reduce all-cause mortality rates compared with controls (relative risk [RR], 0.37 [95% confidence interval, .12-1.13]; very low QoE) or LOS compared with controls (mean difference, 0.72 days [95% confidence interval, −.86 to 2.29 days]; very low QoE). AEs, SAEs, and viral clearance were similar between IVM and control groups (low QoE for all outcomes). Subgroups by severity of COVID-19 or RoB were mostly consistent with main analyses; all-cause mortality rates in 3 RCTs at high RoB were reduced with IVM. Conclusions. Compared with the standard of care or placebo, IVM did not reduce all-cause mortality, LOS, or viral clearance in RCTs in patients with mostly mild COVID-19. IVM did not have an effect on AEs or SAEs and is not a viable option to treat patients with COVID-19.
Supplementary Data Supplementary materials are available at Clinical Infectious Diseases online. Consisting of data provided by the authors to benefit the reader, the posted materials are not copyedited and are the sole responsibility of the authors, so questions or comments should be addressed to the corresponding author.
Note Potential conflicts of interest. All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.
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'abstract': '<jats:title>Abstract</jats:title>\n'
' <jats:sec>\n'
' <jats:title>Background</jats:title>\n'
' <jats:p>We systematically assessed benefits and harms of the use of '
'ivermectin (IVM) in patients with coronavirus disease 2019 (COVID-19).</jats:p>\n'
' </jats:sec>\n'
' <jats:sec>\n'
' <jats:title>Methods</jats:title>\n'
' <jats:p>Published and preprint randomized controlled trials (RCTs) '
'assessing the effects of IVM on adult patients with COVID-19 were searched until 22 March '
'2021 in 5 engines. Primary outcomes were all-cause mortality rate, length of hospital stay '
'(LOS), and adverse events (AEs). Secondary outcomes included viral clearance and severe AEs '
'(SAEs). The risk of bias (RoB) was evaluated using the Cochrane Risk of Bias 2.0 tool. '
'Inverse variance random effect meta-analyses were performed, with quality of evidence (QoE) '
'evaluated using GRADE methods.</jats:p>\n'
' </jats:sec>\n'
' <jats:sec>\n'
' <jats:title>Results</jats:title>\n'
' <jats:p>Ten RCTs (n\u2005=\u20051173) were included. The controls were the '
'standard of care in 5 RCTs and placebo in 5. COVID-19 disease severity was mild in 8 RCTs, '
'moderate in 1, and mild and moderate in 1. IVM did not reduce all-cause mortality rates '
'compared with controls (relative risk [RR], 0.37 [95% confidence interval, .12–1.13]; very '
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'and control groups (low QoE for all outcomes). Subgroups by severity of COVID-19 or RoB were '
'mostly consistent with main analyses; all-cause mortality rates in 3 RCTs at high RoB were '
'reduced with IVM.</jats:p>\n'
' </jats:sec>\n'
' <jats:sec>\n'
' <jats:title>Conclusions</jats:title>\n'
' <jats:p>Compared with the standard of care or placebo, IVM did not reduce '
'all-cause mortality, LOS, or viral clearance in RCTs in patients with mostly mild COVID-19. '
'IVM did not have an effect on AEs or SAEs and is not a viable option to treat patients with '
'COVID-19.</jats:p>\n'
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