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

Ravikirti et al., Journal of Pharmacy & Pharmaceutical Sciences, doi:10.18433/jpps32105

Jan 2021

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RCT with 112 mild and moderate COVID-19 patients in India, showing lower mortality, ventilation, and ICU admission, although not statistically significant due to the small number of events. There was no mortality in the treatment arm (55 patients) versus 7% (4 of 57) in the control arm. The PCR result is subject to confounding by biased loss of followup, with 23 lost in the treatment group and 13 in the control group, and 8 more people in the treatment group discharged before day 6.

Viral load measured by PCR may not accurately reflect infectious virus measured by viral culture. Porter show that viral load early in infection was correlated with infectious virus, but viral load late in infection could be high even with low or undetectable infectious virus. Assessing viral load later in infection may underestimate reductions in infectious virus with treatment.

This is the 11th of 46 COVID-19 RCTs for ivermectin, which collectively show efficacy with p=0.00000014.

This is the 30th of 99 COVID-19 controlled studies for ivermectin, which collectively show efficacy with p<0.0000000001 (1 in 2 sextillion).

1. Porter et al., The ratio between SARS-CoV-2 RNA viral load and culturable viral titer differs depending on stage of infection, medRxiv, doi:10.1101/2023.07.06.23292300.medrxiv.org, doi.org.

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risk of death, 88.7% lower, RR 0.11, p = 0.12, treatment 0 of 55 (0.0%), control 4 of 57 (7.0%), NNT 14, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm).

risk of mechanical ventilation, 79.3% lower, RR 0.21, p = 0.10, treatment 1 of 55 (1.8%), control 5 of 57 (8.8%), NNT 14.

risk of ICU admission, 13.6% lower, RR 0.86, p = 0.80, treatment 5 of 55 (9.1%), control 6 of 57 (10.5%), NNT 70.

risk of no hospital discharge, 88.7% lower, RR 0.11, p = 0.12, treatment 0 of 55 (0.0%), control 4 of 57 (7.0%), NNT 14, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm).

risk of no viral clearance, 11.6% higher, RR 1.12, p = 0.35, treatment 42 of 55 (76.4%), control 39 of 57 (68.4%).

Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates

Ravikirti et al., 9 Jan 2021, Double Blind Randomized Controlled Trial, India, peer-reviewed, 11 authors, study period 1 August, 2020 - 31 October, 2020, average treatment delay 6.1 days, dosage 12mg days 1, 2.

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Evaluation of Ivermectin as a Potential Treatment for Mild to Moderate COVID-19: A Double-Blind Randomized Placebo Controlled Trial in Eastern India

Ranjini Roy, Chandrima Pattadar, Rishav Raj, Neeraj Agarwal, Dr Bijit Biswas, Pramod Kumar Manjhi, Deependra Kumar Rai, Anjani Kumar, Asim Sarfaraz, Ranjini Ravikirti, Chandrima Roy, Rishav Pattadar, Bijit Raj, Neeraj Biswas, Pramod Kumar Agarwal, Manjhi, Kumar Deependra, Rai, Anjani Shyama, Asim Kumar, Sarfaraz

There has been a growing interest in ivermectin ever since it was reported to have an in-vitro activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This trial was conducted to test the efficacy of ivermectin in mild and moderate coronavirus disease 19 . Methods: A double blind, parallel, randomised, placebo-controlled trial conducted among adult COVID-19 patients with mild to moderate disease severity on admission in a COVID dedicated tertiary healthcare of eastern India. Enrolment was done between 1 st August and 31 st October 2020. On day 1 and 2 post enrolment, patients in the intervention arm received ivermectin 12 mg while the patients in the non-interventional arm received placebo tablets. Results: About one-fourth (23.6%) of the patients in the intervention arm and onethird (31.6%) in the placebo arm were tested reverse transcriptase polymerase chain reaction (RTPCR) negative for SARS-CoV-2 on 6 th day. Although this difference was found to be statistically insignificant [rate ratio (RR): 0.8; 95% confidence interval (CI): 0.4-1.4; p=0.348]. All patients in the ivermectin group were successfully discharged. In comparison the same for the placebo group was observed to be 93%. This difference was found to be statistically significant (RR: 1.1; 95% CI; 1.0-1.2; p=0.045). Conclusions: Inclusion of ivermectin in treatment regimen of mild to moderate COVID-19 patients could not be said with certainty based on our study results as it had shown only marginal benefit in successful discharge from the hospital with no other observed benefits.

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