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Efficacy of Ivermectin Treatment on Disease Progression Among Adults With Mild to Moderate COVID-19 and ComorbiditiesThe I-TECH Randomized Clinical Trial

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To identify the key insights or developments described in this article
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Key Points

Question  Does adding ivermectin, an inexpensive and widely available antiparasitic drug, to the standard of care reduce the risk of severe disease in patients with COVID-19 and comorbidities?

Findings  In this open-label randomized clinical trial of high-risk patients with COVID-19 in Malaysia, a 5-day course of oral ivermectin administered during the first week of illness did not reduce the risk of developing severe disease compared with standard of care alone.

Meaning  The study findings do not support the use of ivermectin for patients with COVID-19.

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

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Article Information

Accepted for Publication: January 22, 2022.

Published Online: February 18, 2022. doi:10.1001/jamainternmed.2022.0189

Correction: This article was corrected on April 18, 2022, to report the source of the study drug and to correct a missing minus sign in eTable 1 in Supplement 2.

Corresponding Author: Steven Chee Loon Lim, MRCP, Department of Medicine, Raja Permaisuri Bainun Hospital, Jalan Raja Ashman Shah, 30450 Ipoh, Perak, Malaysia (stevenlimcl@gmail.com).

Author Contributions: Dr S. Lim and Mr King had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: S. Lim, Tan, Chow, Cheah, Cheng, An, Low, Song, Chidambaram, Peariasamy.

Acquisition, analysis, or interpretation of data: S. Lim, Hor, Tay, Mat Jelani, Tan, Ker, Zaid, Cheah, H. Lim, Khalid, Mohd Unit, An, Nasruddin, Khoo, Loh, Zaidan, Ab Wahab, Koh, King, Lai.

Drafting of the manuscript: S. Lim, Hor, Tay, Mat Jelani, Tan, Zaid, H. Lim, An, Low, Ab Wahab, King, Peariasamy.

Critical revision of the manuscript for important intellectual content: S. Lim, Hor, Tan, Ker, Chow, Cheah, Khalid, Cheng, Mohd Unit, An, Nasruddin, Khoo, Loh, Zaidan, Song, Koh, King, Lai, Chidambaram.

Statistical analysis: S. Lim, Hor, Tan, King, Lai.

Administrative, technical, or material support: S. Lim, Hor, Tay, Mat Jelani, Tan, Ker, Chow, Zaid, Cheah, H. Lim, Khalid, Low, Khoo, Loh, Zaidan, Ab Wahab, Song, Koh, Chidambaram.

Supervision: S. Lim, Tan, Ker, Chow, Zaid, Cheng, Khoo, Loh, Song, Peariasamy.

Conflict of Interest Disclosures: None reported.

The I-TECH Study Group: Members of the I-TECH Study Group are listed in Supplement 3.

Data Sharing Statement: See Supplement 4.

Additional Contributions: The authors thank all the investigators at the 21 study sites and the Institute for Clinical Research, Ministry of Health Malaysia, for their immense contribution and support. In addition, we are grateful for the participation of the patients enrolled in this study. We also thank the members of the independent Data and Safety Monitoring Board, namely Petrick Periyasamy, MMed, National University Medical Centre, Malaysia; Lai Hui Pang, BPharm, Institute for Clinical Research, Malaysia; Mohamad Adam Bujang, PhD, Institute for Clinical Research, Malaysia; Wei Hong Lai, PhD, Institute for Clinical Research, Malaysia; and Nurakmal Baharum, BSc, Institute for Clinical Research, Malaysia. They did not receive compensation for their contribution to this study. We also thank Noor Hisham Abdullah, M Surg, Director-General of Health Malaysia, for his permission to publish this study.

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