PMID- 37088312 OWN - NLM STAT- MEDLINE DCOM- 20230718 LR - 20230719 IS - 1600-0641 (Electronic) IS - 0168-8278 (Linking) VI - 79 IP - 2 DP - 2023 Aug TI - A randomized-controlled trial of SOF/VEL/VOX with or without ribavirin for retreatment of chronic hepatitis C. PG - 314-320 LID - S0168-8278(23)00234-9 [pii] LID - 10.1016/j.jhep.2023.04.011 [doi] AB - BACKGROUND & AIMS: The combination of sofosbuvir, velpatasvir and voxilaprevir (SOF/VEL/VOX) is recommended for the retreatment of patients with HCV infection in whom previous direct-acting antiviral (DAA) treatment failed. However, whether ribavirin further increases the therapeutic efficacy of SOF/VEL/VOX retreatment remains unclear. We aimed to test this hypothesis in a randomized-controlled trial. METHODS: We randomly assigned 315 patients with DAA treatment failure from five Egyptian sites into two groups. Group A (n = 158) received SOF/VEL/VOX for 12 weeks, and group B (n = 157) received SOF/VEL/VOX + weight-based ribavirin for 12 weeks. Therapeutic efficacy was defined as SVR12 (sustained virologic response 12 weeks after treatment end). Safety and tolerability were evaluated by monitoring treatment-related adverse events (AEs) and laboratory abnormalities. RESULTS: Males comprised 53.9% of group A and 57.1% of group B (p = 0.58); mean ages were 51.8 and 47.3 years in group A and B, respectively. Seventeen patients in each group were lost to follow-up. SVR12 rates were 87.3% (138/158) by intention-to-treat analysis and 97.8% (138/141) by per-protocol analysis in group A; and 87.9% (138/157) and 98.5% (138/140), respectively, in group B (p = n.s. for intention-to-treat and per-protocol analyses). Both regimens were well-tolerated, with no deaths and only one serious AE (anemia) in group B, which required ribavirin discontinuation. Fifty-five patients in group A vs. 77 in group B experienced any AE (p = 0.002). CONCLUSION: This randomized-controlled trial showed equal, high efficacy of both regimens for the retreatment of previous DAA failures, although ribavirin was associated with more AEs. Therefore SOF/VEL/VOX monotherapy should be the preferred retreatment strategy. CLINCIALTRIALS. GOV NUMBER: NCT04695769. IMPACT AND IMPLICATIONS: HCV treatment guidelines recommend retreatment of direct-acting antiviral (DAA) treatment failures with the combination of sofosbuvir, velpatasvir and voxilaprevir (SOF/VEL/VOX) for 12 weeks. However, whether ribavirin exerts an additional/synergistic effect remains unclear. The present study confirmed that SOF/VEL/VOX without ribavirin is the best regimen for retreatment of DAA treatment failures, and thus will help guide clinicians caring for patients who are not cured with a first course of DAA therapy. CI - Copyright (c) 2023 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved. FAU - El-Kassas, Mohamed AU - El-Kassas M AD - Endemic Medicine Department, Faculty of Medicine, Helwan University, Cairo, Egypt. FAU - Emadeldeen, Mohammed AU - Emadeldeen M AD - Gastroenterology and Hepatology Department, National Hepatology & Tropical Medicine Research Institute (NHTMRI), Cairo, Egypt. FAU - Hassany, Mohamed AU - Hassany M AD - Gastroenterology and Hepatology Department, National Hepatology & Tropical Medicine Research Institute (NHTMRI), Cairo, Egypt. FAU - Esmat, Gamal AU - Esmat G AD - Hepatology and Endemic Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt. FAU - Gomaa, Ahmed Ali AU - Gomaa AA AD - Department of Tropical Medicine and Gastroenterology, Faculty of Medicine, Fayoum University, Fayoum, Egypt. FAU - El-Raey, Fathiya AU - El-Raey F AD - Department of Hepatology, Gastroenterology and Infectious Disease, Damietta Faculty of Medicine, Al-Azhar University, Damietta, Egypt. FAU - Congly, Stephen E AU - Congly SE AD - Liver Unit, University of Calgary Cumming School of Medicine, Calgary, Alberta, Canada. FAU - Liu, Hongqun AU - Liu H AD - Liver Unit, University of Calgary Cumming School of Medicine, Calgary, Alberta, Canada. FAU - Lee, Samuel S AU - Lee SS AD - Liver Unit, University of Calgary Cumming School of Medicine, Calgary, Alberta, Canada. Electronic address: samlee@ucalgary.ca. LA - eng SI - ClinicalTrials.gov/NCT04695769 PT - Journal Article PT - Randomized Controlled Trial DEP - 20230423 PL - Netherlands TA - J Hepatol JT - Journal of hepatology JID - 8503886 RN - WJ6CA3ZU8B (Sofosbuvir) RN - 0 (Antiviral Agents) RN - 49717AWG6K (Ribavirin) RN - 0570F37359 (voxilaprevir) RN - KCU0C7RS7Z (velpatasvir) SB - IM MH - Male MH - Humans MH - Female MH - Sofosbuvir/adverse effects MH - Antiviral Agents/adverse effects MH - *Hepatitis C, Chronic/drug therapy MH - Ribavirin/adverse effects MH - Treatment Outcome MH - Drug Therapy, Combination MH - Hepacivirus/genetics MH - *Hepatitis C/drug therapy MH - Retreatment MH - Genotype OTO - NOTNLM OT - DAA treatment failure OT - Ribavirin OT - SOF/VEL/VOX OT - direct-acting antivirals OT - hepatitis C virus EDAT- 2023/04/24 00:41 MHDA- 2023/07/18 13:07 CRDT- 2023/04/23 19:31 PHST- 2022/12/25 00:00 [received] PHST- 2023/04/03 00:00 [revised] PHST- 2023/04/04 00:00 [accepted] PHST- 2023/07/18 13:07 [medline] PHST- 2023/04/24 00:41 [pubmed] PHST- 2023/04/23 19:31 [entrez] AID - S0168-8278(23)00234-9 [pii] AID - 10.1016/j.jhep.2023.04.011 [doi] PST - ppublish SO - J Hepatol. 2023 Aug;79(2):314-320. doi: 10.1016/j.jhep.2023.04.011. Epub 2023 Apr 23.