METHODS: We included 446 SARS-CoV-2 RT-PCR-positive patients taking at least one treatment drug for COVID-19 within a period of one month (March-April 2020). In addition to COVID-19-related treatment (HCQ/PI), concomitant drugs with risks of QTc prolongation were considered. We defined QTc prolongation as QTc interval of ≥470 ms in postpubertal males, and ≥480 ms in postpubertal females.

RESULTS AND DISCUSSION: QTc prolongation events occurred in 28/446 (6.3%) patients with an incidence rate of 1 case per 100 person-days. A total of 26/28 (93%) patients who had prolonged QTc intervals received at least two pro-QT drugs. Multivariate analysis showed that HCQ and PI combination therapy had five times higher odds of QTc prolongation as compared to HCQ-only therapy after controlling for age, cardiovascular disease, SIRS and the use of concurrent QTc-prolonging agents besides HCQ and/or PI (OR 5.2; 95% CI, 1.11-24.49; p = 0.036). Independent of drug therapy, presence of SIRS resulted in four times higher odds of QTc prolongation (OR 4.3; 95% CI, 1.66-11.06; p = 0.003). In HCQ-PI combination group, having concomitant pro-QT drugs led to four times higher odds of QTc prolongation (OR 3.8; 95% CI, 1.53-9.73; p = 0.004). Four patients who had prolonged QTc intervals died but none were cardiac-related deaths.

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.