Ongoing Living Update of Potential COVID-19 Therapeutics: summary of rapid systematic reviews - 11 August 2020

    Publication year: 2020

    More than 200 therapeutic options or their combinations are being investigated in more than 1,700 clinical trials. In this review we examined 30 therapeutic options. Findings from the RECOVERY Trial showed that low doses of dexamethasone (6 mg of oral or intravenous preparation once daily for 10 days) significantly reduced mortality by one-third in ventilated patients and by one fifth in patients receiving oxygen only. The anticipated RECOVERY. Trial findings and WHO’s SOLIDARITY Trial findings both show no benefit via use of hydroxychloroquine and lopinavir/ritonavir in terms of reducing 28-day mortality or reduced time to clinical improvement or reduced adverse events. Currently, there is no evidence of benefit in critical outcomes (i.e. reduction in mortality) from any therapeutic option (though remdesivir is revealing promise as one option based on 2 randomized controlled trials) and that conclusively allows for safe and effective use to mitigate or eliminate the causative agent of COVID-19. Currently, as to ivermectin, we found 1 in vitro study and 4 observational studies that were largely confounded (nonrandomized), and lacked the methodological rigor to allow much confidence in the results. They were pre-print and non-peer reviewed and were judged to be of high risk of bias and very low quality of evidence. The researchers concluded in large part that the findings could be considered hypothesis testing and urged the conduct of large sample sized RCTs to assess any clinical benefit. Currently, as to favipiravir, we found 1 RCT and 2 observational studies. The results were inconclusive for benefits of favipiravir, and sample sizes were small and results came via largely preprints and non-peer reviewed publications. The 2 nonrandomized observational designs revealed sub-optimal methods with no optimal adjustments, masking, or stratification. A recent release by Glenmark announced promising results from a Phase 3 Clinical Trial of favipiravir in patients with mild to moderate COVID-19. A Phase 3 RCT demonstrates statistically significant faster time to clinical improvement with favipiravir treatment compared to control (n=150 patients).