Efficacy and safety of single-dose ivermectin in mild-to-moderate COVID-19: the double-blind, randomized, placebo-controlled CORVETTE-01 trial
Tatsuhiko Wada, Makoto Hibino, Hiromi Aono, Shunsuke Kyoda, Yosuke Iwadate, Eri Shishido, Keisuke Ikeda, Nana Kinoshita, Yasuki Matsuda, Sakiko Otani, Ryo Kameda, Kenta Matoba, Miwa Nonaka, Mika Maeda, Yuji Kumagai, Junya Ako, Masayoshi Shichiri, Katsuhiko Naoki, Masato Katagiri, Masashi Takaso, Masatsugu Iwamura, Kazuhiko Katayama, Takeshi Miyatsuka, Yasushi Orihashi, Kunihiro Yamaoka
Frontiers in Medicine, doi:10.3389/fmed.2023.1139046
Background: To investigate whether ivermectin inhibits SARS-CoV-2 proliferation in patients with mild-to-moderate COVID-19 using time to a negative COVID-19 reverse transcription-polymerase chain reaction (RT-PCR) test. Methods: CORVETTE-01 was a double-blind, randomized, placebo-controlled study (August 2020-October 2021) conducted in Japan. Overall, 248 patients diagnosed with COVID-19 using RT-PCR were assessed for eligibility. A single oral dose of ivermectin (200 μg/kg) or placebo was administered under fasting. The primary outcome was time to a negative COVID-19 RT-PCR test result for SARS-CoV-2 nucleic acid, assessed using stratified log-rank test and Cox regression models. Results: Overall, 112 and 109 patients were randomized to ivermectin and placebo, respectively; 106 patients from each group were included in the full analysis set (male [%], mean age: 68.9%, 47.9 years [ivermectin]; 62.3%, 47.5 years [placebo]). No significant difference was observed in the occurrence of negative RT-PCR tests between the groups (hazard ratio, 0.96; 95% confidence interval [CI] 0.70-1.32; p = 0.785). Median (95% CI) time to a negative RT-PCR test was 14.0
Ethics statement The studies involving human participants were reviewed and approved by the IRB of Kitasato University Shirokane Campus, affiliation: Kitasato University. The patients/participants provided their written informed consent to participate in this study.
Author contributions KY contributed towards conceptualization and drafting the work. YK contributed towards conceptualization, drafting the work, and revising it critically for important intellectual content. MS, TM, JA, KN, MI, MT, MM, MK, and KK contributed towards conceptualization, drafting the work, and revising it critically for important intellectual content. MH, HA, MN, KI, ES, YI, NK, SK, SO, RK, KM, and YM contributed towards acquisition, analysis, or interpretation of data for the work, drafting the work, and revising it critically for important intellectual content. TW contributed towards conceptualization, acquisition, analysis, or interpretation of data for the work, and drafting the work. YO contributed towards the data analysis, drafting the work, and revising it critically for important intellectual content. All authors provide approval for publication of the content and agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
Conflict of interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could..
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'abstract': '<jats:sec><jats:title>Background</jats:title><jats:p>To investigate whether ivermectin '
'inhibits SARS-CoV-2 proliferation in patients with mild-to-moderate COVID-19 using time to a '
'negative COVID-19 reverse transcription-polymerase chain reaction (RT-PCR) '
'test.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>CORVETTE-01 was a '
'double-blind, randomized, placebo-controlled study (August 2020–October 2021) conducted in '
'Japan. Overall, 248 patients diagnosed with COVID-19 using RT-PCR were assessed for '
'eligibility. A single oral dose of ivermectin (200\u2009 μg/kg) or placebo was administered '
'under fasting. The primary outcome was time to a negative COVID-19 RT-PCR test result for '
'SARS-CoV-2 nucleic acid, assessed using stratified log-rank test and Cox regression '
'models.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Overall, 112 and '
'109 patients were randomized to ivermectin and placebo, respectively; 106 patients from each '
'group were included in the full analysis set (male [%], mean age: 68.9%, 47.9 years '
'[ivermectin]; 62.3%, 47.5 years [placebo]). No significant difference was observed in the '
'occurrence of negative RT-PCR tests between the groups (hazard ratio, 0.96; 95% confidence '
'interval [CI] 0.70–1.32; <jats:italic>p</jats:italic>\u2009=\u20090.785). Median (95% CI) '
'time to a negative RT-PCR test was 14.0 (13.0–16.0) and 14.0 (12.0–16.0) days for ivermectin '
'and placebo, respectively; 82.1% and 84% of patients achieved negative RT-PCR tests, '
'respectively.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>In '
'patients with COVID-19, single-dose ivermectin was ineffective in decreasing the time to a '
'negative RT-PCR test.</jats:p></jats:sec><jats:sec><jats:title>Clinical Trial '
'Registration</jats:title><jats:p><jats:ext-link>ClinicalTrials.gov</jats:ext-link>, '
'NCT04703205.</jats:p></jats:sec>',
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