Purpose / DescriptionThe ASTRAL-4 trial was a randomized, open-label phase 3 trial designed to examine the safety and efficacy of the fixed-dose combination of sofosbuvir-velpatasvir with or without ribavirin in patients with genotype 1, 2, 3, 4, or 6 chronic HCV infection and decompensated cirrhosis. Treatment-naïve and treatment-experienced patients with Child-Pugh-Turcotte (CTP) class B disease were randomized to one of three arms: (1) sofosbuvir-velpatasvir for 12 weeks (n=90), (2) sofosbuvir-velpatasvir plus ribavirin for 12 weeks (n=87), or (3) sofosbuvir-velpatasvir for 24 weeks (n=90). All three regimens were highly efficacious among genotype 1 patients (88%, 96%, and 92% respectively) and genotypes 2, 4 and 6 patients (100%, 100%, and 86% respectively). Notably among patients with genotype 3, the treatment groups without ribavirin had lower SVR12 rates of 50% (each) compared with 85% in the sofosbuvir-velpatasvir plus ribavirin arm. Overall, the CTP scores improved over baseline in 47%, remained unchanged in 42%, and worsened in 11%. A total of 22 patients experienced virologic failure; most (n=18) had NS5A variants at the time of failure with the Y93H/N occurring most frequently.