Efficacy of Ivermectin Treatment on Disease Progression Among Adults With Mild to Moderate COVID-19 and Comorbidities
Steven Lim, Chee Peng Hor, Kim Heng Tay, Anilawati Mat Jelani, W. Tan, Hong Bee Ker, Ting Soo Chow, Masliza Zaid, Wee Kooi Cheah, Han Hua Lim, Khairil Erwan Khalid, Joo Thye Cheng, Hazfadzila Mohd Unit, Noralfazita An, Azraai Bahari Nasruddin, Lee Lee Low, Song Weng Ryan Khoo, Jia Hui Loh, Nor Zaila Binti Zaidan, Suhaila Ab Wahab, L Song, Hui Moon Koh, Teck Long King, Nai Ming Lai, Suresh Kumar Chidambaram, Kalaiarasu M. Peariasamy, I-TECH Study Group, Wen Yea Hwong, Ee Vien Low, Mohan Dass Pathmanathan, Muhammad Luqman Hamzah, Yew Chung Chan, James Yau Hon Voo, Chun Fei Yap, Yon Quan Chan, Lee Kuen Vun, Kian K. Kong, Yi Fang Lim, Yee Jie Teoh, Ammar Rashidi Abdullah, Anitha Ramadas, Chee Loon Leong, Noor Hidayu Wahab, Nadiah Ismail, Ismaliza Ismail, Tung Meng Lee, Pei Jie Khoo, Sook Hui Phua, Prethivan Pillai Gopalakrishnan, Sangeetha Jaya Selan, Iswaran Ampalakan, Jen Fai Khuan, Wan Nur Farra’Ain Abdul Rashid, Siti Sha’ada Zakaria, Kalaiarasan Gemini, Haslina Burahan, Thaanveer Singh Santokh Singh, Noorfarzlina Jaafar, Nor Atikah Mohd Shukri, Syaza Izhar Hisham, Sheng Hao Teow, Chit Yeh Lim, Shageetha Rajantran, Siti Izzatul Annis Kamaruddin, Izarin Izmir Izhar, N Mustapha, Zulkefli Mohamad, Seri Rabiatul Nur Abu Salim, Delarina Frimawati Othman Andu, Nurnadiah Kamarudin, Karamjit Kaur Sarban Singh, Eek Poei Tay, Siti Hir Huraizah Md Tahir, Shalini Vijayasingham, Yik Zhi Kum, Peter Andrew Natarajan, Yih Harng Soh, Syed Omar Farouk Syed Alwi, Hemaarubeni Murugan, Chuan Huan Chuah, Shin Wuei Tan, Kar Nim Leong, Peng Shyan Wong, Wendy Tyng Tyng Chen, R. Ng, Yen Li Lim, Farah Nadiah Bidin, Mann Leon Chin, Han Lin Guan, Mohd Hafiz Mohamad Rasli, Rafidah Abdullah, Mohd Akmal Jamaludin, Nabilah Mohd Shohaime, Syafiqah Mohd Mansor, Ruhaizad Rasliza, Lisa Mohamed Nor, Kah Mean Thong, Balasurindiran Muniandy, Pamela Varn Teing Saw, Kah Shuen Thong
Abstract
Importance: Ivermectin, an inexpensive and widely available antiparasitic drug, is prescribed to treat COVID-19. Evidence-based data to recommend either for or against the use of ivermectin are needed. Objective: To determine the efficacy of ivermectin in preventing progression to severe disease among high-risk patients with COVID-19. Design, Setting, and Participants: The Ivermectin Treatment Efficacy in COVID-19 High-Risk Patients (I-TECH) study was an open-label randomized clinical trial conducted at 20 public hospitals and a COVID-19 quarantine center in Malaysia between May 31 and October 25, 2021. Within the first week of patients' symptom onset, the study enrolled patients 50 years and older with laboratory-confirmed COVID-19, comorbidities, and mild to moderate disease. Interventions: Patients were randomized in a 1:1 ratio to receive either oral ivermectin, 0.4 mg/kg body weight daily for 5 days, plus standard of care (n = 241) or standard of care alone (n = 249). The standard of care consisted of symptomatic therapy and monitoring for signs of early deterioration based on clinical findings, laboratory test results, and chest imaging. Main Outcomes and Measures: The primary outcome was the proportion of patients who progressed to severe disease, defined as the hypoxic stage requiring supplemental oxygen to maintain pulse oximetry oxygen saturation of 95% or higher. Secondary outcomes of the trial included the rates of mechanical ventilation, intensive care unit admission, 28-day in-hospital mortality, and adverse events. Results: Among 490 patients included in the primary analysis (mean [SD] age, 62.5 [8.7] years; 267 women [54.5%]), 52 of 241 patients (21.6%) in the ivermectin group and 43 of 249 patients (17.3%) in the control group progressed to severe disease (relative risk [RR], 1.25; 95% CI, 0.87-1.80; P = .25). For all prespecified secondary outcomes, there were no significant differences between groups. Mechanical ventilation occurred in 4 (1.7%) vs 10 (4.0%) (RR, 0.41; 95% CI, 0.13-1.30; P = .17), intensive care unit admission in 6 (2.4%) vs 8 (3.2%) (RR, 0.78; 95% CI, 0.27-2.20; P = .79), and 28-day in-hospital death in 3 (1.2%) vs 10 (4.0%) (RR, 0.31; 95% CI, 0.09-1.11; P = .09). The most common adverse event reported was diarrhea (14 [5.8%] in the ivermectin group and 4 [1.6%] in the control group). Conclusions and Relevance: In this randomized clinical trial of high-risk patients with mild to moderate COVID-19, ivermectin treatment during early illness did not prevent progression to severe disease. The study findings do not support the use of ivermectin for patients with COVID-19. Trial Registration: ClinicalTrials.gov Identifier: NCT04920942.