A randomized double-blind placebo-controlled clinical trial of nitazoxanide for treatment of mild or moderate COVID-19
Rossignol et al.,
A randomized double-blind placebo-controlled clinical trial of nitazoxanide for treatment of mild or moderate..,
eClinicalMedicine, doi:10.1016/j.eclinm.2022.101310 (date from earlier preprint), NCT04486313
RCT with 184 outpatients treated with an extended release formulation of nitazoxanide, and 195 controls, showing lower hospitalization and progression to severe disease with treatment. There was one COVID-19 related death in the treatment arm. 600mg twice daily for five days.
NCT04486313 (history).
risk of death, 206.0% higher, RR 3.06, p = 0.49, treatment 1 of 184 (0.5%), control 0 of 195 (0.0%), continuity correction due to zero event (with reciprocal of the contrasting arm), COVID-19 deaths.
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risk of hospitalization, 78.8% lower, RR 0.21, p = 0.22, treatment 1 of 184 (0.5%), control 5 of 195 (2.6%), NNT 49.
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risk of severe case, 84.9% lower, RR 0.15, p = 0.07, treatment 1 of 184 (0.5%), control 7 of 195 (3.6%), NNT 33.
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risk of severe case, 83.9% lower, RR 0.16, p = 0.07, treatment 1 of 112 (0.9%), control 7 of 126 (5.6%), NNT 21, high-risk subgroup.
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time to sustained recovery, 7.3% higher, relative time 1.07, p = 0.88, treatment 184, control 195, primary outcome.
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Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
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Rossignol et al., 31 Mar 2022, Double Blind Randomized Controlled Trial, USA, peer-reviewed, 5 authors, study period August 2020 - February 2021, average treatment delay 1.83 days, trial
NCT04486313 (history).
Abstract: Articles
A randomized double-blind placebo-controlled clinical
trial of nitazoxanide for treatment of mild or moderate
COVID-19
Jean-François Rossignol,a Matthew C. Bardin,a Jessica Fulgencio,a Dena Mogelnicki,a and Christian Brechot a,b,c*, for the Vanguard Study Group 1
a
Romark Institute of Medical Research, Tampa, FL, United States
University of South Florida, College of Medicine, Tampa, FL, United States
c
Global Virus Network, United States
b
Summary
Background There is an urgent need for treatments of mild or moderate COVID-19 in an outpatient setting.
Methods A randomized double-blind placebo-controlled clinical trial in 36 centers in the U.S. between August 2020
and February 2021 investigated the safety and effectiveness of oral nitazoxanide 600 mg twice daily for five days in
outpatients with symptoms of mild or moderate COVID-19 enrolled within 72 h of symptom onset (ClinicalTrials.
gov NCT04486313). Efficacy endpoints were time to sustained clinical recovery (TSR, a novel primary endpoint) and
proportion of participants progressing to severe illness within 28 days (key secondary).
eClinicalMedicine
2022;45: 101310
Published online xxx
https://doi.org/10.1016/j.
eclinm.2022.101310
Findings 1092 participants were enrolled. 379 with laboratory-confirmed SARS-CoV-2 infection were analyzed. In
the primary analysis, median (IQR) TSR were 13¢3 (6¢3, >21) and 12¢4 (7¢2, >21) days for the nitazoxanide and placebo groups, respectively (p = 0¢88). 1 of 184 (0¢5%) treated with nitazoxanide progressed to severe illness compared
to 7 of 195 (3¢6%) treated with placebo (key secondary analysis, odds ratio 5¢6 [95% CI 0¢7 - 46¢1], relative risk reduction 85%, p = 0¢07). In the pre-defined stratum with mild illness at baseline, nitazoxanide-treated participants experienced reductions in median TSR (3¢1 days, p = 0¢09) and usual health (5¢2 days, p < 0¢01) compared to placebo.
Nitazoxanide was safe and well tolerated.
Interpretation Further trials with larger numbers are warranted to evaluate efficacy of nitazoxanide therapy in preventing progression to severe illness in patients at high risk of severe illness and reducing TSR in patients with mild
illness.
Copyright Published by Elsevier Ltd. This is an open access article under the CC BY license (http://
creativecommons.org/licenses/by/4.0/)
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