A Pragmatic, Randomized Controlled Trial of Oral Antivirals for the Treatment of Chronic Hepatitis C: The PRIORITIZE Study.

Background & aims Multiple direct-acting antiviral (DAA) regimens are available to treat hepatitis C virus (HCV), genotype 1 infection. However, comparative effectiveness from randomized controlled trials of DAA regimens is unavailable. Approach & Results We conducted a pragmatic randomized controlled trial (NCT02786537) to compare the effectiveness of DAAs for HCV genotype 1a or 1b on viral response, safety, tolerability, and medication non-adherence. Adults with compensated liver disease, HCV genotype 1, not pregnant or breast feeding, and with health insurance likely to cover ledipasvir/sofosbuvir (LDV/SOF) were recruited from 34 U.S. viral hepatitis clinics. Participants were randomized (± ribavirin) to ledipasvir/sofosbuvir (LDV/SOF), elbasvir/grazoprevir (EBR/GZR), and paritaprevir/ritonavir/ombitasvir+dasabuvir (PrOD, treatment arm stopped early). Primary outcomes included sustained viral response at 12 weeks (SVR12), clinician-recorded adverse events, patient-reported symptoms, and medication non-adherence. Between June 2016 and March 2018, 1609 participants were randomized. Among 1128 participants who received ≥ 1 dose of EBR/GZR or LDV/SOF (± ribavirin), SVR12 were 95.2% [95% CI, 92.8 to 97.6] and 97.4% [95% CI, 95.5 to 99.2] respectively, with a difference estimate of 2.2% [ -0.5, 4.7%], falling within the 'equivalence' interval [-5, 5%]. While most (56%) participants experienced adverse events, few were serious (4.2%) or severe (1.8%). In the absence of ribavirin, discontinuations due to adverse events were rare. Patient-reported symptoms and medication non-adherence were similar. Study limitations were drop-out due to insurance denial and lost to follow-up after treatment, limiting the ability to measure SVR12. Conclusions This pragmatic trial demonstrated high SVR12 for participants treated with EBR/GZR and LDV/SOF with few adverse effects. Overall, the two regimens were equivalent in effectiveness. The results support current HCV guidelines that do not distinguish between ribavirin-free EBR/GZR or LDV/SOF.