Ivermectin for the treatment of COVID-19: A systematic review and meta-analysis of randomized controlled trials
Roman et al.
, Ivermectin for the treatment of COVID-19: A systematic review and meta-analysis of randomized controlled..
, Clinical Infectious Diseases, doi:10.1093/cid/ciab591 (date from earlier preprint) (meta analysis)
This is a severely flawed meta analysis. An open letter signed
by 40 physicians detailing errors and flaws, and requesting retraction, can
be found at [trialsitenews.com]
See also [bird-group.org]
Authors cherry-pick to include only 4 studies reporting
non-zero mortality and they initially claimed a mortality RR of 1.11
[0.16-7.65]. However, they reported incorrect values for Niaee et al.,
claiming an RR of 6.51 [2.18-19.45], when the correct RR for Niaee et al. is
0.18 [0.06-0.55]. After correction, their cherry-picked studies show >60%
mortality reduction, however authors did not correct the conclusion.
Similarly, for viral clearance and NCT04392713 (history)
, they report
20/41 treatment, 18/45 control, whereas the correct day 7 clearance numbers
are 37/41 and 20/45 (sum of clearance @72hrs and @7 days), or 17/41 and
2/45 @72 hrs.
The duration of hospital stay for Niaee et al. is also
incorrectly reported, showing a lower duration for the control group.
All of the errors are in one direction - incorrectly reporting
lower than actual efficacy for ivermectin. Authors claim to include all RCTs
excluding prophylaxis, however they only include 10 of the 24 non-prophylaxis
RCTs (28 including prophylaxis at the time of publication). Authors actually
reference meta analyses that do include the missing RCTs, so they should be
aware of the missing RCTs.
The authors state that they have no conflicts of interest on
medRxiv, however Dr. Pasupuleti’s affiliation is Cello Health, whose website
notes that they provide services such as
“brand and portfolio commercial strategy for biotech and pharma”
that their clients are "24 of the top 25 pharmaceutical
Only one of these errors has been partially fixed as of 5/29 -
the Niaee RR was corrected, but the associated conclusion was not. Other
errors have not been corrected. Comments on this article appear to be
censored, with zero comments posted as of July 5.
Roman et al., 28 Jun 2021, peer-reviewed, 6 authors.
Abstract: Clinical Infectious Diseases
Ivermectin for the Treatment of Coronavirus Disease 2019:
A Systematic Review and Meta-analysis of Randomized
Health Outcomes, Policy, and Evidence Synthesis (HOPES) Group, University of Connecticut School of Pharmacy, Storrs, Connecticut, USA; 2Universidad Científica del Sur, Lima, Peru; 3Centro
de Investigación, Instituto Peruano de Oncología y Radioterapia, San Isidro, Lima, Peru; 4Cello Health, Yardley, Pennsylvania, USA; 5Unidad de Revisiones Sistemáticas y Meta-análisis, Guías de
Práctica Clínica y Evaluaciones de Tecnologías Sanitarias (URSIGET), Vicerrectorado de Investigación, Universidad San Ignacio de Loyola, La Molina, Lima, Peru; 6Division of Infectious Diseases,
Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil; 7Department of Neurology, Instituto de Infectologia Emílio Ribas, São Paulo, Brazil; and 8Laboratory
of Medical Investigation, Unit 49, Hospital das Clinicas, Universidade de São Paulo, São Paulo, Brazil
Background. We systematically assessed benefits and harms of the use of ivermectin (IVM) in patients with coronavirus disease
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
Keywords. ivermectin; SARS-CoV-2; COVID-19; mortality; meta-analysis.
The coronavirus disease 2019 (COVID-19) pandemic represents a
global sanitary, social, and economic challenge. However, scientific
advances have also amplified deficiencies and misinformation .
Biological plausibility, pathophysiological considerations, in vitro
research, observational studies, and/or clinical trials with heterogeneous quality were used to evaluate several repurposed drugs repurposed for indications different from the approved ones. Some
policy makers and regulatory institutions authorized emergency
use of unproven COVID-19 treatments; the use of some of these
treatments has been heavily politicized in some regions [2, 3].
Ivermectin (IVM) is a semisynthetic,..
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