I-TECH: Ivermectin found not effective against severe COVID-19 progression

Ivermectin did not prevent progression to severe COVID-19 in high-risk patients with mild-to-moderate COVID-19, according to a nationwide study.

The I-TECH* open-label randomized clinical trial, involving 490 patients across 20 Malaysian public hospitals and one COVID-19 quarantine centre, found no significant difference in disease progression between patients randomized to a group receiving 5-day course of daily oral ivermectin 0.4 mg/kg body weight plus standard of care (n=241), versus a control group receiving standard of care alone (n=249). [JAMA Intern Med doi:10.1001/jamainternmed.2022.0189]

The study enrolled patients aged ≥50 years between May and October 2021 with at least one comorbidity, presenting with COVID-19 clinical severity stage 2 or 3 (WHO clinical progression scale 2–4) within 7 days of symptom onset. The primary outcome was progression to severe disease, defined in the study as hypoxia requiring supplementary oxygen to maintain pulse oximetry oxygen saturation (SpO₂) ≥95 percent.

Overall, 21.6 percent (n=52) of patients in the ivermectin group progressed to severe disease, versus 17.3 percent (n=43) of patients in the control group. Among patients who progressed to severe disease, the mean time from enrollment to onset was similar between both groups (mean [standard deviation, SD], ivermectin 3.2 [2.4] days vs control 2.9 [1.8] days; mean difference, 0.3; 95 percent confidence interval [CI], -0.6–1.2; p=0.51).

By day 5 of enrollment, both groups also had similar proportions of patients achieving complete symptom resolution (risk ratio, RR 0.97; 95 percent CI, 0.82–1.15; p=0.72). There were no significant differences in secondary outcomes (ie, mechanical ventilation, ICU admission, and 28-day hospital mortality) between the two groups.

Furthermore, adverse events (AEs) occurred more frequently in the ivermectin group (13.7 percent) versus the control group (4.4 percent), with diarrhea being the most common in both (5.8 percent vs 1.6 percent).

“We found no evidence that ivermectin was efficacious in reducing the risk of severe disease,” said the study authors. “Our findings are consistent with the results of the IVERCOR-COVID19 trial, which found that ivermectin was ineffective in reducing the risk of hospitalization.” [BMC Infect Dis 2021;21(1):635]

They added that while prior RCTs of ivermectin involving 400 or more patients were focused on outpatient treatment, the I-TECH study, which involved hospitalized patients, allowed for better adherence to ivermectin treatment and observation of the results.

The mean duration of symptoms at enrollment was 5.1 days (SD 1.3 days). Oral ivermectin was administered to the study group during the first week of illness. In total, 232 patients completed all five doses, with others receiving less or withdrawing due to adverse events.

Thirteen deaths occurred during the study, with nine attributed to severe COVID-19 pneumonia and four to nosocomial sepsis. No deaths were attributed to ivermectin treatment.

Study limitations acknowledged by the authors included the open-label design, which might have caused AE underreporting in the control group and overreporting in the ivermectin group. Furthermore, the study was not designed to assess ivermectin’s effect on COVID-19 mortality.

Overall, the authors concluded that the I-TECH findings did not support ivermectin use in high risk hospitalized patients with mild to moderate COVID-19.