Sergio M Borgia1, Janet Dearden2, Eric M Yoshida3, Stephen D Shafran4, Ashley Brown5, Ziv Ben-Ari6, Matthew E Cramp7, Curtis Cooper8, Matthew Foxton9, Conrado Fernandez Rodriguez10, Rafael Esteban11, Robert Hyland12, Sophia Lu12, Brian J Kirby12, Amy Meng12, Svetlana Markova12, Hadas Dvory-Sobol12, Anu O Osinusi12, Rafael Bruck13, Javier Ampuero14, Stephen D Ryder15, Kosh Agarwal16, Raymond Fox17, David Shaw18, Shariq Haider19, Bernard Willems20, Yoav Lurie21, Jose Luis Calleja22, Edward J Gane23. 1. William Osler Health System, Brampton Civic Hospital, Brampton, ON, Canada. Electronic address: sergio.borgia@williamoslerhs.ca. 2. Barts Health Hospital Trust, London, UK. 3. Gordon and Leslie Diamond Health Care Centre, Vancouver, BC, Canada. 4. Department of Medicine, University of Alberta, Edmonton, AB, Canada. 5. Imperial College Healthcare NHS Trust, London, UK. 6. Sheba Medical Center, Ramat Gan, Israel. 7. South West Liver Unit and Plymouth University Peninsula Schools of Medicine and Dentistry, Plymouth, UK. 8. Ottawa Hospital Research Institute, Ottawa, ON, Canada. 9. Chelsea and Westminster Hospital NHS Foundation Trust, London, UK. 10. Hospital Universitario Fundación Alcorcón, Madrid, Spain. 11. Hospital Universitario Vall d'Hebron, Barcelona, Spain. 12. Gilead Sciences, Inc., Foster City, CA, USA. 13. Tel Aviv Medical Center and Tel Aviv University, Tel Aviv, Israel. 14. Hospital Universitario Virgen del Rocío, Sevilla, Spain. 15. NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and Nottingham Digestive Diseases Centre, University of Nottingham, Nottingham, UK. 16. Institute of Liver Studies, King's College Hospital NHS Foundation Trust, London, UK. 17. Gartnavel General Hospital, Glasgow, UK. 18. Royal Adelaide Hospital, Adelaide, SA, Australia. 19. Hamilton Health Sciences, Juravinski Hospital and Cancer Centre, Hamilton, ON, Canada. 20. Centre Hospitalier de l'Université de Montréal, Montreal, QC, Canada. 21. Shaare Zedek Medical Center, Jerusalem, Israel. 22. Hospital Universitario Puerta De Hierro, Madrid, Spain. 23. Auckland City Hospital, Auckland, New Zealand.
Abstract
BACKGROUND & AIMS: Although off-label use of sofosbuvir-containing regimens occurs regularly in patients with hepatitis C virus (HCV) infection undergoing dialysis for severe renal impairment or end-stage renal disease (ESRD), these regimens are not licensed for this indication, and there is an absence of dosing recommendations in this population. This study evaluated the safety and efficacy of sofosbuvir/velpatasvir in patients with HCV infection with ESRD undergoing dialysis. METHODS: In this phase II, single-arm study, 59 patients with genotype 1-6 HCV infection with ESRD undergoing hemodialysis or peritoneal dialysis received open-label sofosbuvir/velpatasvir (400 mg/100 mg) once daily for 12 weeks. Patients were HCV treatment naive or treatment experienced without cirrhosis or with compensated cirrhosis. Patients previously treated with any HCV NS5A inhibitor were not eligible. The primary efficacy endpoint was the proportion of patients achieving sustained virologic response (SVR) 12 weeks after discontinuation of treatment (SVR12). The primary safety endpoint was the proportion of patients who discontinued study drug due to adverse events. RESULTS: Overall, 56 of 59 patients achieved SVR12 (95%; 95% CI 86-99%). Of the 3 patients who did not achieve SVR12, 2 patients had virologic relapse determined at post-treatment Week 4 (including 1 who prematurely discontinued study treatment), and 1 patient died from suicide after achieving SVR through post-treatment Week 4. The most common adverse events were headache (17%), fatigue (14%), nausea (14%), and vomiting (14%). Serious adverse events were reported for 11 patients (19%), and all were deemed to be unrelated to sofosbuvir/velpatasvir. CONCLUSIONS: Treatment with sofosbuvir/velpatasvir for 12 weeks was safe and effective in patients with ESRD undergoing dialysis. LAY SUMMARY: Sofosbuvir/velpatasvir is a combination direct-acting antiviral that is approved for treatment of patients with hepatitis C virus (HCV) infection. Despite the lack of dosing recommendations, sofosbuvir-containing regimens (including sofosbuvir/velpatasvir) are frequently used for HCV-infected patients undergoing dialysis. This study evaluated the safety and efficacy of sofosbuvir/velpatasvir for 12 weeks in patients with HCV infection who were undergoing dialysis. Treatment with sofosbuvir/velpatasvir was safe and well tolerated, resulting in a cure rate of 95% in patients with HCV infection and end-stage renal disease. Clinical Trial Number: NCT03036852.
BACKGROUND & AIMS: Although off-label use of sofosbuvir-containing regimens occurs regularly in patients with hepatitis C virus (HCV) infection undergoing dialysis for severe renal impairment or end-stage renal disease (ESRD), these regimens are not licensed for this indication, and there is an absence of dosing recommendations in this population. This study evaluated the safety and efficacy of sofosbuvir/velpatasvir in patients with HCV infection with ESRD undergoing dialysis. METHODS: In this phase II, single-arm study, 59 patients with genotype 1-6 HCV infection with ESRD undergoing hemodialysis or peritoneal dialysis received open-label sofosbuvir/velpatasvir (400 mg/100 mg) once daily for 12 weeks. Patients were HCV treatment naive or treatment experienced without cirrhosis or with compensated cirrhosis. Patients previously treated with any HCV NS5A inhibitor were not eligible. The primary efficacy endpoint was the proportion of patients achieving sustained virologic response (SVR) 12 weeks after discontinuation of treatment (SVR12). The primary safety endpoint was the proportion of patients who discontinued study drug due to adverse events. RESULTS: Overall, 56 of 59 patients achieved SVR12 (95%; 95% CI 86-99%). Of the 3 patients who did not achieve SVR12, 2 patients had virologic relapse determined at post-treatment Week 4 (including 1 who prematurely discontinued study treatment), and 1 patient died from suicide after achieving SVR through post-treatment Week 4. The most common adverse events were headache (17%), fatigue (14%), nausea (14%), and vomiting (14%). Serious adverse events were reported for 11 patients (19%), and all were deemed to be unrelated to sofosbuvir/velpatasvir. CONCLUSIONS: Treatment with sofosbuvir/velpatasvir for 12 weeks was safe and effective in patients with ESRD undergoing dialysis. LAY SUMMARY:Sofosbuvir/velpatasvir is a combination direct-acting antiviral that is approved for treatment of patients with hepatitis C virus (HCV) infection. Despite the lack of dosing recommendations, sofosbuvir-containing regimens (including sofosbuvir/velpatasvir) are frequently used for HCV-infectedpatients undergoing dialysis. This study evaluated the safety and efficacy of sofosbuvir/velpatasvir for 12 weeks in patients with HCV infection who were undergoing dialysis. Treatment with sofosbuvir/velpatasvir was safe and well tolerated, resulting in a cure rate of 95% in patients with HCV infection and end-stage renal disease. Clinical Trial Number: NCT03036852.
Authors: Liangying Gan; Dongyu Wang; Brian Bieber; Keith McCullough; Michel Jadoul; Ronald L Pisoni; Fanfan Hou; Xinling Liang; Zhaohui Ni; Xiaonong Chen; Yuqing Chen; Li Zuo Journal: Front Med (Lausanne) Date: 2022-06-15
Authors: Meghan E Sise; Ian Strohbehn; Donald Chute; Kathleen E Corey; Dahlene N Fusco; Venkata S Sabbisetti; Sushrut S Waikar; Raymond T Chung Journal: Hepatol Commun Date: 2020-06-04