Effect of Early Treatment with Ivermectin among Patients with Covid-19
New study in Brazil, high quality.
From the abstract:
Background
The efficacy of ivermectin in preventing hospitalization or extended observation in an emergency setting among outpatients with acutely symptomatic coronavirus disease 2019 (Covid-19), the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is unclear.
Methods
We conducted a double-blind, randomized, placebo-controlled, adaptive platform trial involving symptomatic SARS-CoV-2–positive adults recruited from 12 public health clinics in Brazil. Patients who had had symptoms of Covid-19 for up to 7 days and had at least one risk factor for disease progression were randomly assigned to receive ivermectin (400 μg per kilogram of body weight) once daily for 3 days or placebo. (The trial also involved other interventions that are not reported here.) The primary composite outcome was hospitalization due to Covid-19 within 28 days after randomization or an emergency department visit due to clinical worsening of Covid-19 (defined as the participant remaining under observation for >6 hours) within 28 days after randomization.
Results
A total of 3515 patients were randomly assigned to receive ivermectin (679 patients), placebo (679), or another intervention (2157). Overall, 100 patients (14.7%) in the ivermectin group had a primary-outcome event, as compared with 111 (16.3%) in the placebo group (relative risk, 0.90; 95% Bayesian credible interval, 0.70 to 1.16). Of the 211 primary-outcome events, 171 (81.0%) were hospital admissions. Findings were similar to the primary analysis in a modified intention-to-treat analysis that included only patients who received at least one dose of ivermectin or placebo (relative risk, 0.89; 95% Bayesian credible interval, 0.69 to 1.15) and in a per-protocol analysis that included only patients who reported 100% adherence to the assigned regimen (relative risk, 0.94; 95% Bayesian credible interval, 0.67 to 1.35). There were no significant effects of ivermectin use on secondary outcomes or adverse events.
Conclusions
Treatment with ivermectin did not result in a lower incidence of medical admission to a hospital due to progression of Covid-19 or of prolonged emergency department observation among outpatients with an early diagnosis of Covid-19.
Reference: Reis, G., Silva, E., Silva, D., Thabane, L., Milagres, A., & Ferreira, T. et al. (2022). Effect of Early Treatment with Ivermectin among Patients with Covid-19. New England Journal Of Medicine. https://doi.org/10.1056/nejmoa2115869
This is the sort of quality study that gives verifiable results, and it's clear now that ivermectin does not live up to the hopes that many people had.
Within the study a careful explanation of ivermectin trials is made that lays out the problems thus far with ivermectin being used clinically in this way:
More than 60 randomized trials of ivermectin for the treatment of Covid-19 have been registered, and findings have been reported for as many as 31 clinical trials. The results have been discordant, and various review groups interpret the evidence differently — some advocating for benefits of ivermectin, and others reticent to conclude a benefit. However, most trials have been small, and several have been withdrawn from publication owing to concerns about credibility.
As stated in the study:
We conducted this randomized, adaptive platform trial for the investigation of the efficacy of repurposed treatments for Covid-19 among adult outpatients at high risk for hospitalization. The trial was designed and conducted in partnership with local public health authorities from 12 cities in Brazil in order to simultaneously test potential treatments for early Covid-19 with the use of a master protocol. A master protocol defines prospective decision criteria for discontinuing interventions for futility, stopping owing to superiority of an intervention over placebo, or adding new interventions. Interventions that have been evaluated in this trial thus far include hydroxychloroquine and lopinavir–ritonavir (both in protocol 1) and metformin, ivermectin administered for 1 day, ivermectin administered for 3 days, doxazosin, pegylated interferon lambda, and fluvoxamine (all in protocol 2), as compared with matching placebos. The full trial protocol with the statistical analysis plan has been published previously and is available with the full text of this article at NEJM.org.
It was very carefully randomised.
An independent pharmacist conducted the randomization at a central trial facility, from which the trial sites requested randomization by means of text message. Patients underwent randomization by means of a block randomization procedure for each participating site, with stratification according to age (<50 years or ≥50 years). The trial team, site staff, and patients were unaware of the randomized assignments. The active-drug and placebo pills were packaged in identically shaped bottles and labeled with alphabetic letters corresponding to ivermectin or placebo. Participants who were randomly assigned to receive placebo were assigned to a placebo regimen (ranging from 1 day to 14 days) that corresponded with that of a comparable active-treatment group in the trial. Only the pharmacist who was responsible for randomization was aware of which letter referred to which assignment.
Between the placebo group and ivermectin group, there were no significant differences with regard to viral clearance, risk of hospitalisation, time to hospitalisation, number of days in hospital, time to clinical recovery, risk of death, time to death, number of days with mechanical ventilation, or incidence of adverse events during the treatment period.
Early treatment (treatment regime beginning within 3 days of symptoms onset) showed no observed benefit.
