Muhammad Radzi Abu Hassan, Nor Asiah Muhamad, Noor Syahireen Mohammed, Mohd Azri Mohd Suan, Deanna Nadia Zulkifli Supramaniam, Sathya Rao Jogulu, Muhammad Firdaus Md Salleh, Shahrul Aiman Soelar, Izzah Athirah Rosli, Fatin Norhasny Leman, Nor Soleha Mohd Dali, Nur Hasnah Maamor, Nor Fariza Ngah, Huan‐Keat Chan
OBJECTIVE: To determine whether an 8-week regimen of sofosbuvir/ravidasvir is non-inferior to the standard 12-week regimen in non-cirrhotic chronic hepatitis C virus (HCV) infection. DESIGN OR METHODS: We conducted a multicenter open-label, randomized, non-inferiority clinical trial across nine hospitals and 17 primary healthcare centers in Malaysia. Adults aged 18-69 years with chronic HCV infection without cirrhosis were randomized (1:1) to receive 8 or 12 weeks of sofosbuvir/ravidasvir. The primary endpoint was sustained virologic response 12 weeks post-treatment (SVR12). The non-inferiority margin was 5%. The primary analysis was performed in the modified intention-to-treat population, excluding participants with missing primary endpoint data. RESULTS: Between March 2021, and March 2023, 322 participants were randomized (161 per arm). Among those with available SVR12 results, 142/152 (93.4%) in the 8-week group and 143/153 (93.5%) in the 12-week group (difference: -0.04%; 90% CI: -4.94% to 4.85%; P = 0.047), demonstrating non-inferiority. Efficacy was consistent across genotype, baseline viral load, and HIV co-infection subgroups. Treatment-emergent adverse events were comparable and predominantly mild; no treatment-related serious adverse events occurred. CONCLUSION: An 8-week sofosbuvir/ravidasvir regimen achieved SVR12 comparable to 12 weeks in non-cirrhotic adults with chronic HCV infection and was well tolerated. Further pragmatic and cost-effectiveness studies are needed to inform large-scale implementation. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04885855 [09/05/2021].