High Dose Ivermectin for the Early Treatment of COVID-19 (COVIER Study): A Randomised, Double-Blind, Multicentre, Phase II, Dose-Finding, Proof of Concept Clinical Trial
Early terminated 89 patient RCT with 29 high dose and 32 very high dose ivermectin patients, showing dose dependent viral load reduction, although not reaching statistical significance due to early termination. Since most patients have low viral load at day 7, there is little room for improvement with a treatment at day 7. Intermediate results may show significantly greater improvement, but are not provided. Authors note that ivermectin remained safe even at the very high dose used, although tolerability was reduced. 3 patients were hospitalized in the very high dose ivermectin arm (and 1 in the high dose arm) versus 0 in the control arm. While this result is not statistically significant, it may be in part due to randomization failure because 9 patients were randomized at the hospital for very high dose ivermectin versus 4 in the control arm, suggesting higher baseline severity. Supplementary data is not currently available. COVIER. NCT04438850
Buonfrate et al., 9/6/2021, Double Blind Randomized Controlled Trial, Italy, Europe, preprint, 18 authors, dosage 1200μg/kg days 1-5, arm B 600µg/kg, arm C 1200µg/kg.
risk of hospitalization, 600.0% higher, RR 7.00, p = 0.30, treatment 4 of 58 (6.9%), control 0 of 29 (0.0%), continuity correction due to zero event (with reciprocal of the contrasting arm).
relative change in viral load, RR 0.69, p = 0.10, treatment 30, control 29, day 7, arm C.
relative change in viral load, RR 0.86, p = 0.12, treatment 28, control 29, day 7, arm B.
Effect extraction follows pre-specified rules
prioritizing more serious outcomes. For an individual study the most serious
outcome may have a smaller number of events and lower statistical signficance,
however this provides the strongest evidence for the most serious outcomes
when combining the results of many trials.