A randomized-controlled trial of SOF/VEL/VOX with or without ribavirin for retreatment of chronic hepatitis C

Abstract

The combination of sofosbuvir, velpatasvir and voxilaprevir (SOF/VEL/VOX) is recommended retreatment for patients with hepatitis C virus (HCV) infection who failed previous direct-acting antiviral (DAA) treatment. However, whether ribavirin further increases the therapeutic efficacy of SOF/VEL/VOX retreatment remains unclear. We aimed to test this hypothesis by a randomized controlled trial. We randomly assigned 315 patients with DAA treatment failure from 5 Egyptian sites into two groups. Group A (n=158) received SOF/VEL/VOX for 12 weeks, and group B (n=157) received SOF/VEL/VOX + weight-based ribavirin for 12 weeks. Therapeutic efficacy was defined as SVR12 (undetectable HCV RNA 12 weeks after treatment completion). Safety and tolerability were evaluated by monitoring treatment-related adverse events (AEs) and laboratory abnormalities. Seventeen patients in each group were lost to follow-up. SVR12 rates by intention-to-treat (ITT) were 87.3% (138/158), and by per-protocol analysis, 97.8% (138/141) in group A; and 87.9% (138/157) and 98.5% (138/140) in group B (p=NS for ITT and PP). Males comprised 53.9% of group A, and 57.1% in group B (p=0.58), with mean ages of 51.8 and 47.3 years in group A and B, respectively. Both regimens were well-tolerated, with no deaths and only one serious AE (anemia) in group B requiring ribavirin discontinuation. Fifty-five patients in group A vs. 77 in group B experienced any adverse events (p=0.002). This randomized controlled trial showed equal, high efficacy of both regiments in retreating previous DAA failures, although ribavirin was associated with more adverse events. Therefore SOF/VEL/VOX monotherapy should be the preferred retreatment strategy. HCV treatment guidelines recommend retreating DAA treatment failures with the combination of sofosbuvir, velpatasvir and voxilaprevir (SOF/VEL/VOX) for 12 weeks. However, whether ribavirin exerts an additional/synergistic effect remains unclear. The present study confirmed that SOF/VEL/VOX without ribavirin is the best regimen for retreating DAA treatment failures, and thus will help clinicians caring for patients who are not cured with a first course of DAA therapy. CLINCIALTRIALS. NCT04695769.