Ivermectin as a potential treatment for mild to moderate COVID-19 – A double blind randomized placebo-controlled trial

Abstract

ObjectiveIvermectin has been suggested as a treatment for COVID-19.This randomised control trial was conducted to test the efficacy of Ivermectin in the treatment of mild and moderate COVID-19.DesignParallel, double blind, randomised, placebo controlled trial Setting: A tertiary care dedicated COVID-19 hospital in Bihar, IndiaParticipantsAdult patients (> 18 years) admitted with mild to moderate COVID 19 disease (saturation > 90% on room air, respiratory rate < 30 and no features of shock) with no contraindications to ivermectin and willing to participate in the studyInterventionPatients in the intervention arm were given ivermectin 12 mg on day 1 and day 2 of admission. Patients in the placebo arm were given identical looking placebo tablets. Rest of the treatment was continued as per the existing protocol and the clinical judgment of the treating teams.Outcome MeasuresThe primary outcome measure was a negative RT-PCR test for SARS-CoV-2 on day 6 of admission. The secondary outcome measures were symptom status on day 6, discharge status on day 10, admission to ICU, need for invasive mechanical ventilation and in-hospital mortality.ResultsA total of 115 patients were enrolled for the study of which 112 were included in the final analysis. Of them, 55 were randomised to the intervention arm while 57 were randomised to the placebo arm. There was no significant difference in the baseline characteristics of the two arms. There was no significant difference in the primary outcome, i.e. negative RT-PCR status on day 6 between the two groups. Similarly, there was no significant difference between the two groups in most of the secondary outcome measures, viz. symptom status on day 6, discharge status on day 10, admission to ICU, and need for invasive mechanical ventilation. However, while there was no in-hospital mortality in the intervention arm, there were 4 deaths in the placebo arm. As a result, all patients in the intervention arm (n=56) were successfully discharged as compared to 93.1% (n=54/58) in the placebo arm (RR 1.1, 95% CI 1.0 to 1.2, p=0.019).ConclusionThere was no difference in the primary outcome i.e. negative RT-PCR status on day 6 of admission with the use of ivermectin. However, a significantly higher proportion of patients were discharged alive from the hospital when they received ivermectin.Strengths and Limitations of the StudyThis study was randomised and double blind, thereby minimizing the chance of bias.All outcome measures except symptom status on day 6 were objective and placebo control was used for comparison.Only single repeat RT-PCR was done. So median time to viral clearance in the two groups could not be calculated.Severe cases were not included in the study.

Proxalutamide Significantly Accelerates Viral Clearance and Reduces Time to Clinical Remission in Patients with Mild to Moderate COVID-19: Results from a Randomized, Double-Blinded, Placebo-Controlled Trial

“…Nevertheless, almost three times as many subjects in the Proxalutamide group compared to those from the placebo group tested negative for SARS-CoV-2 on Day 7. Compared to other treatments with in-vitro anti-SARS-CoV-2 activity or preliminary clinical data, to date, no other drug has demonstrated the ability to enhance viral clearance to the extent observed for Proxalutamide [12,14]. Similarly, time to clinical remission was vastly improved in the subjects given Proxalutamide versus the placebo.…”

Meta-analysis of randomized trials of ivermectin to treat SARS-CoV-2 infection

“…Three different endpoints were used to analyze viral clearance: the percentage of patients undetectable on a set day (Table 3A), the number of days from randomization to negativity (Table 3B), and other measures such as cycle time (Ct) values and dose-response correlations (Table 3C). The Kirti [26] and Okumus [23] trials included viral load analysis only in a subset of patients. The effects of ivermectin on viral clearance were generally smaller when dosed on only one day.…”

Key summary of German national treatment guidance for hospitalized COVID-19 patients

“…Evidence : Numerous preprints are available online reporting solely on viral load reduction rather than clinically relevant endpoints or with significant methodological issues and a high risk of bias (exemplary [ 57 – 59 ]). At the time of consensus for this recommendation, February 2021, only one peer-reviewed publication of a randomized controlled trial with a total of 72 patients was available for consideration [ 60 ].…”