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

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.

Figure.. Screening, Enrollment, Randomization, and Treatment Assignment

^aThe study inclusion and exclusion criteria were made known to physicians at study sites to facilitate prescreening of patients. ^bThe number of patients counseled by study investigators was not collected. ^cOne patient had onset of COVID-19 symptoms 8 days prior to randomization, which exceeded the first 7 days of illness inclusion criterion. Another patient had a COVID-19 rapid test antigen positive result but polymerase chain reaction negative result. This was before a protocol amendment that included positive COVID-19 antigen test result as alternative inclusion criteria if polymerase chain reaction testing was not done or was negative. ^dPatient was found to have acute coronary syndrome after randomization but before commencement of ivermectin therapy. Acute medical emergency was an exclusion criterion. ^ePatient was diagnosed of dengue fever with NS-1 antigen positive. Concomitant viral infection was an exclusion criterion. ^fIn the intervention arm, only patients who received at least 1 dose of ivermectin were included in the modified intention-to-treat analysis.