By Neha MathurJan 3 2023Reviewed by Danielle Ellis, B.Sc. In a recent study published in the NEJM, researchers presented the results of a phase III randomized controlled trial of oral severe acute respiratory syndrome coronavirus 2 antiviral VV116. They conducted this trial during the recent outbreak caused by the new SARS-CoV-2 variant Omicron , which had a higher immunity-evading potential.
Currently, available oral analogs of remdesivir are GS-621763, VV116, and ATV006. VV116, a deuterated remdesivir hydrobromide, showed good oral bioavailability and anti-SARS-CoV-2 activity in preclinical trials. The trial executioners ensured that all the site staff, including researchers involved in endpoint drug assessments except those who dispensed the trial drugs directly, remained blinded to drug assignment groups until unblinding in May 2022. However, study participants remained blinded to their drug assignment throughout the study.
The WHO clinical progression scale had scores ranging between zero to 10, whereas total symptom scores ranged between zero and 33, with higher scores indicating greater severity for all 11 targeted COVID-19 symptoms. The study investigators assessed these scores before the trial-drug dispensation. They continued these assessments until Day 28 of the study or resolution of targeted symptoms , whichever was earlier.
They maintained the lower boundary while doing the computations for the 95% confidence interval for the hazard ratio of the primary endpoint analysis >0.8, estimated with the Cox proportional-hazards model. Likewise, they used the Kaplan–Meier method to estimate the average time to sustain COVID-19 clinical recovery and 95% CI. The noninferiority margin corresponded to 6.875 days taken for sustained clinical recovery from COVID-19, and a minimum of 724 events ensured 85% statistical power.