1. Efficacy and safety of sofosbuvir-velpatasvir with or without ribavirin in HCV-infected Japanese patients with decompensated cirrhosis: an open-label phase 3 trial.
- Author
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Takehara T, Sakamoto N, Nishiguchi S, Ikeda F, Tatsumi T, Ueno Y, Yatsuhashi H, Takikawa Y, Kanda T, Sakamoto M, Tamori A, Mita E, Chayama K, Zhang G, De-Oertel S, Dvory-Sobol H, Matsuda T, Stamm LM, Brainard DM, Tanaka Y, and Kurosaki M
- Subjects
- Adult, Aged, Aged, 80 and over, Antiviral Agents administration & dosage, Antiviral Agents adverse effects, Carbamates adverse effects, Drug Combinations, Female, Genotype, Hepacivirus genetics, Heterocyclic Compounds, 4 or More Rings adverse effects, Humans, Japan, Liver Cirrhosis virology, Male, Middle Aged, Ribavirin adverse effects, Sofosbuvir adverse effects, Sustained Virologic Response, Treatment Outcome, Carbamates administration & dosage, Hepatitis C drug therapy, Heterocyclic Compounds, 4 or More Rings administration & dosage, Liver Cirrhosis drug therapy, Ribavirin administration & dosage, Sofosbuvir administration & dosage
- Abstract
Background: In Japan, hepatitis C virus (HCV)-infected patients with decompensated cirrhosis currently have no treatment options. In this Phase 3 study, we evaluated sofosbuvir-velpatasvir with or without ribavirin for 12 weeks in patients with any HCV genotype and decompensated cirrhosis [Child-Pugh-Turcotte (CPT) class B or C] in Japan., Methods: Patients were randomized 1:1 to receive sofosbuvir-velpatasvir with or without ribavirin for 12 weeks. Randomization was stratified by CPT class and genotype. Sustained virologic response 12 weeks following completion of treatment (SVR12) was the primary efficacy endpoint., Results: Of the 102 patients enrolled, 57% were treatment naive, 78% and 20% had genotype 1 and 2 HCV infection, respectively, and 77% and 20% had CPT class B and C cirrhosis, respectively, at baseline. Overall, 61% of patients were female and the mean age was 66 years (range 41-83). SVR12 rates were 92% (47/51) in each group. Among patients who achieved SVR12, 26% had improved CPT class from baseline to posttreatment week 12. Most adverse events (AEs) were consistent with clinical sequelae of advanced liver disease or known toxicities of ribavirin. Four patients (8%) who received sofosbuvir-velpatasvir and seven (14%) who received sofosbuvir-velpatasvir plus ribavirin experienced a serious AE. The 3 deaths (bacterial sepsis, gastric varices hemorrhage, hepatocellular carcinoma) were attributed to liver disease progression., Conclusion: Sofosbuvir-velpatasvir for 12 weeks provides a highly effective and well-tolerated therapy for Japanese patients with HCV and decompensated cirrhosis. Ribavirin did not improve efficacy but increased toxicity.
- Published
- 2019
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