A group of researchers from prominent institutions, including Mayo Clinic, Rochester and Government Medical College in India, recently conducted a comprehensive meta-analysis evaluating the benefits and possible risks associated with the use of ivermectin as a treatment option targeting SARS-CoV-2, the virus behind COVID-19. The authors recently shared the results with medRxiv. Although not peer reviewed nor published as of yet, the findings were of interest and are now available on the preprint server medRxiv. Their efforts are premised on the challenge that despite over a year of intensive R&D spend in the billions of dollars, there is still no effective therapy for the COVID-19 virus. The authors acknowledge that ivermectin has demonstrated positive results in several observational studies and after a review of 38 studies covering 15,002 patients, the research team came to the conclusion that their analysis points to ivermectin as a possibly effective adjuvant therapy in helping to reduce mortality—only in those patients with mild-to-moderate clinical presentation of COVID-19 based on high certainty of evidence from RCTs subgroup analysis. However, certainty of evidence was very low in observational studies. Decreased need for ICU admissions and mechanical ventilation were observed, however the findings were not statistically significant. An analysis of adverse events was inconclusive. Due to high heterogeneity in analysis and low to moderate level of certainty of evidence, they suggest use of Ivermectin in COVID-19 patients should depend on bedside clinician’s judgement.
Led by corresponding author Vikas Bansal, MBBS, MPH, Assistant Professor of Medicine, Division of Pulmonary Medicine and Critical Care at Mayo Clinic (Rochester, MN), the team reviewed a total of 38 clinical trials involving 15,002 patients. Apparently, ivermectin influenced a lower mortality rate: those in the ivermectin arms of study experienced lower mortality as compared to the non-ivermectin arms (OR 0.39, 95% CI 0.22-0.70; I2 84=81%). A subgroup analysis of 12 clinical trials based on severity-based data revealed that the ivermectin arm showed morality benefit (OR 0.33, 95% CK 0.15-0.72; 12 85 = 53%) as well as benefit in the mild/moderate subgroup (OR 0.10, 95% CI 0.03-0.33; I2 86 =0%).
Moreover, the team uncovered that the benefit of ivermectin in lowering the need for ICU admission (OR 0.48, 95% CI 0.17-1.37; I2 87 =59%) as well as mechanical ventilation (OR 0.64, 95% CI 0.40-1.04; I2 88 =17%), however, it was not statistically significant.
They concluded that this meta-analysis revealed that Ivermectin may in fact represent an effective adjuvant therapy in reducing mortality, especially in those patients classified in the mild-to-moderate stage. They proposed that there is a need of pragmatic practice embedded platform trials to test Ivermectin and other re-purposed and novel therapies specifically in severe COVID-19 patients. TrialSite notes that in most places around the world, about 90% of the COVID-19 infections fall into this category.
TrialSite briefly spoke with corresponding author Vikas Bansal who shared that this was an investigator-initiated study as he and colleagues sought to better understand the efficacy of ivermectin given the pandemic and the fact that in countries like India, wide-spread vaccination may take longer and hence low cost therapies can be of great public health benefit.
Dr. Bansal shared with TrialSite that the team has submitted the manuscript to the Critical Care Medicine Journal, which is the premier peer-reviewed, scientific publication of Society of Critical Care Medicine’s official Journal for peer review and publishing.
Vikas Bansal, MBBS, MPH, Assistant Professor of Medicine, Division of Pulmonary Medicine and Critical Care at Mayo Clinic, Rochester
Smruti Karale, MBBS, Department of Internal Medicine, Government Medical College-Kolhapur, Kolhapur, Maharashtra, India
Rahul Kashyap, MBBS, MBA, Assistant Professor of Anesthesiology, Department of Anesthesiology and Critical Care Medicine at Mayo Clinic, Rochester
@VikasBa23474580, @Dr_SRKashyap, @romilsingh1892, @AyssTekin