Rafael Esteban1, Juan A Pineda2, Jose Luis Calleja3, Marta Casado4, Manuel Rodríguez5, Juan Turnes6, Luis Enrique Morano Amado7, Rosa Maria Morillas8, Xavier Forns9, Juan Manuel Pascasio Acevedo10, Raul J Andrade11, Antonio Rivero12, José Antonio Carrión13, Sabela Lens9, Mar Riveiro-Barciela14, Brian McNabb15, Gulan Zhang15, Gregory Camus15, Luisa M Stamm15, Diana M Brainard15, G Mani Subramanian15, Maria Buti16. 1. Hospital Universitario Vall d'Hebron and CIBERehd del Instituto Carlos III, Barcelona, Spain. Electronic address: resteban@vhebron.net. 2. Unit of Infectious Diseases and Microbiology, Hospital Universitario Virgen de Valme, Sevilla, Spain. 3. Liver Unit, Hospital Universitario Puerta de Hierro, Majadahonda, Spain, and Universidad Autónoma de Madrid, Madrid, Spain, and CIBERehd. 4. Complejo Hospitalario Torrecárdenas, Almeria, Spain. 5. Hospital Universitario Central de Asturias, Oviedo, Spain. 6. Gastroenterology and Hepatology Department, Complejo Hospitalario Universitario de Pontevedra and IISGS, Pontevedra, Spain. 7. Unit of Infectious Diseases, University Hospital Alvaro Cunqueiro, Institute of Health Research Galicia Sur, Vigo, Spain. 8. Hospital Universitari Germans Trias i Pujol, Badalona, Spain, and CIBERehd. 9. Liver Unit, Hospital Clínic Barcelona, and University of Barcelona, and IDIBAPS, and CIBERehd. 10. Clinical Management Unit of Digestive Diseases, IBIS, CIBERehd, Hospital Universitario Virgen del Rocío, Sevilla, Spain. 11. Unidad de Gestión Clínica de Enfermedades Digestivas, Hospital Universitario Virgen de la Victoria, Universidad de Málaga, and IBIMA, and CIBERehd. 12. Hospital Universitario Reina Sofia/IMIBIC/UCO, Cordoba, Spain. 13. Liver Section, Gastroenterology Department, Hospital del Mar, Universitat Autònoma de Barcelona, IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain. 14. Liver Unit Department of Internal Medicine, Hospital Universitari Vall d'Hebron and Universitat Autònoma de Barcelona, Barcelona, Spain, and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain. 15. Gilead Sciences, Inc, Foster City, California. 16. Hospital Universitario Vall d'Hebron and CIBERehd del Instituto Carlos III, Barcelona, Spain.
Abstract
BACKGROUND & AIMS: In phase 3 trials and real-world settings, smaller proportions of patients with genotype 3 hepatitis C virus (HCV) infection and cirrhosis have a sustained virologic response 12 weeks after treatment (SVR12) with the combination of sofosbuvir and velpatasvir than in patients without cirrhosis. It is unclear whether adding ribavirin to this treatment regimen increases SVRs in patients with genotype 3 HCV infection and cirrhosis. METHODS: We performed a phase 2 trial of 204 patients with genotype 3 HCV infection and compensated cirrhosis (mean age 51± 7.4 years) at 29 sites in Spain from August 19, 2016 through April 18, 2017. Patients were assigned to groups given sofosbuvir and velpatasvir for 12 weeks (n = 101) or sofosbuvir and velpatasvir plus ribavirin for 12 weeks (n = 103). The primary efficacy end point was SVR12. RESULTS: The overall rates of SVR12 were 91% (92 of 101; 95% CI 84-96) for the sofosbuvir-velpatasvir group and 96% (99 of 103; 95% CI 90-99) for the sofosbuvir-velpatasvir plus ribavirin group. In the sofosbuvir-velpatasvir group, a smaller proportion of patients with baseline resistance-associated substitutions (RASs) in nonstructural protein 5A (NS5A) achieved an SVR12 (84%) than did patients without (96%). In the sofosbuvir-velpatasvir plus ribavirin group, baseline RASs had less effect on the proportion of patients with an SVR12 (96% for patients with baseline RASs; 99% for patients without). The most common adverse events (which occurred in ≥10% of patients) were asthenia (12%) in the sofosbuvir-velpatasvir group and asthenia (27%), headache (24%), and insomnia (12%) in the sofosbuvir-velpatasvir plus ribavirin group. CONCLUSIONS: Consistent with findings from previous studies, a high rate of patients (91% and 96%) with genotype 3 HCV infection and compensated cirrhosis achieved an SVR12 with sofosbuvir and velpatasvir, with or without ribavirin. Of patients treated with sofosbuvir and velpatasvir without ribavirin, fewer patients with baseline NS5A RASs achieved an SVR12 compared with patients without baseline NS5A. ClinicalTrials.govNCT02781558.
RCT Entities:
BACKGROUND & AIMS: In phase 3 trials and real-world settings, smaller proportions of patients with genotype 3 hepatitis C virus (HCV) infection and cirrhosis have a sustained virologic response 12 weeks after treatment (SVR12) with the combination of sofosbuvir and velpatasvir than in patients without cirrhosis. It is unclear whether adding ribavirin to this treatment regimen increases SVRs in patients with genotype 3 HCV infection and cirrhosis. METHODS: We performed a phase 2 trial of 204 patients with genotype 3 HCV infection and compensated cirrhosis (mean age 51 ± 7.4 years) at 29 sites in Spain from August 19, 2016 through April 18, 2017. Patients were assigned to groups given sofosbuvir and velpatasvir for 12 weeks (n = 101) or sofosbuvir and velpatasvir plus ribavirin for 12 weeks (n = 103). The primary efficacy end point was SVR12. RESULTS: The overall rates of SVR12 were 91% (92 of 101; 95% CI 84-96) for the sofosbuvir-velpatasvir group and 96% (99 of 103; 95% CI 90-99) for the sofosbuvir-velpatasvir plus ribavirin group. In the sofosbuvir-velpatasvir group, a smaller proportion of patients with baseline resistance-associated substitutions (RASs) in nonstructural protein 5A (NS5A) achieved an SVR12 (84%) than did patients without (96%). In the sofosbuvir-velpatasvir plus ribavirin group, baseline RASs had less effect on the proportion of patients with an SVR12 (96% for patients with baseline RASs; 99% for patients without). The most common adverse events (which occurred in ≥10% of patients) were asthenia (12%) in the sofosbuvir-velpatasvir group and asthenia (27%), headache (24%), and insomnia (12%) in the sofosbuvir-velpatasvir plus ribavirin group. CONCLUSIONS: Consistent with findings from previous studies, a high rate of patients (91% and 96%) with genotype 3 HCV infection and compensated cirrhosis achieved an SVR12 with sofosbuvir and velpatasvir, with or without ribavirin. Of patients treated with sofosbuvir and velpatasvir without ribavirin, fewer patients with baseline NS5A RASs achieved an SVR12 compared with patients without baseline NS5A. ClinicalTrials.govNCT02781558.
Authors: Jing Hong Loo; Wen Xin Flora Xu; Jun Teck Low; Wei Xuan Tay; Le Shaun Ang; Yew Chong Tam; Prem Harichander Thurairajah; Rahul Kumar; Yu Jun Wong Journal: World J Hepatol Date: 2022-06-27
Authors: Alessandra Mangia; Scott Milligan; Mandana Khalili; Stefano Fagiuoli; Stephen D Shafran; Fabrice Carrat; Denis Ouzan; George Papatheodoridis; Alnoor Ramji; Sergio M Borgia; Heiner Wedemeyer; Ruggero Losappio; Francisco Pérez-Hernandez; Nicole Wick; Robert S Brown; Pietro Lampertico; Karen Doucette; Ioanna Ntalla; Heribert Ramroth; Michael Mertens; Kim Vanstraelen; Juan Turnes Journal: Liver Int Date: 2020-06-09 Impact factor: 5.828
Authors: Elise J Smolders; Anouk M E Jansen; Peter G J Ter Horst; Jürgen Rockstroh; David J Back; David M Burger Journal: Clin Pharmacokinet Date: 2019-10 Impact factor: 6.447
Authors: Eleanor Barnes; Michael Pavlides; Arjun N A Jayaswal; Christina Levick; Jane Collier; Elizabeth M Tunnicliffe; Matthew D Kelly; Stefan Neubauer Journal: Abdom Radiol (NY) Date: 2020-11-28