Efficacy and safety of ivermectin in patients with mild COVID-19 in Japan and Thailand
M.D Hiroshige Mikamo, M.D Satoshi Takahashi, M.D Yuka Yamagishi, Ph.D Akihiro Hirakawa, M.D Toshiyuki Harada, M.D Hirotaka Nagashima, M.D Chiaki Noguchi, M.D Kentaro Masuko, M.D Hiromitsu Maekawa, M.D Tatsuhiko Kashii, Hiroyuki Ohbayashi, Shinichiro Hosokawa, Katsuyuki Maejima, Masaya Yamato, Weerawat Manosuthi, Supachai Paiboonpol, Hideki Suganami, Ryohei Tanigawa, Hitoshi Kawamura
Journal of Infection and Chemotherapy, doi:10.1016/j.jiac.2023.12.012
Background: Ivermectin is an antiparasitic drug administered to hundreds of millions of people worldwide. Fundamental research suggests that ivermectin is effective against coronavirus disease 2019 (COVID-19); therefore, we investigated the efficacy and safety of ivermectin as a COVID-19 treatment option.
Methods: This multi-regional (Japan and Thailand), multicenter, placebo-controlled, randomized, double-blind, parallel-group, Phase III study evaluated the efficacy and safety of ivermectin in patients with mild COVID-19 (IVERMILCO Study). The participants took a specified number of the investigational product (ivermectin or placebo) tablets of, adjusted to a dose of 0.3-0.4 mg/kg, orally on an empty stomach once daily for three days. The primary efficacy endpoint was the time at which clinical symptoms first showed an improving trend by 168 h after investigational product administration.
Results: A total of 1,030 eligible participants were assigned to receive the investigational product; 502 participants received ivermectin and 527 participants received a placebo. The primary efficacy endpoint was approximately 96 h (approximately four days) for both ivermectin and placebo groups, which did not show statistically significant difference (stratified log-rank test, p=0.61). The incidence of adverse events and adverse drug reactions did not show statistically significant differences between the ivermectin and placebo groups (chi-square test, p=0.97, p=0.59).
Conclusions: The results show that ivermectin(0.3-0.4 mg/kg), as a treatment for patients with mild COVID-19, is ineffective; however, its safety has been confirmed for participants, J o u r n a l P r e -p r o o f Confidential including minor participants of 12 years or older. (IVERMILCO Study ClinicalTrials.gov number, NCT05056883.
Conflict of Interest assistance with an earlier version of the manuscript and Kowa employees, Masaya Tanahashi and Tatsuya Muto for statistical analysis and interpretation of this study results. We also thank to Editage (www.editage.com) for English language editing.
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