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Lookup NU author(s): Professor Stuart McPhersonORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2021 Cooke GS et al.Background: The World Health Organization (WHO) has identified the need for a better understanding of which patients with hepatitis C virus (HCV) can be cured with ultrashort course HCV therapy. Methods: A total of 202 individuals with chronic HCV were randomised to fixed-duration shortened therapy (8 weeks) vs variable-duration ultrashort strategies (VUS1/2). Participants not cured following first-line treatment were retreated with 12 weeks' sofosbuvir/ledipasvir/ribavirin. The primary outcome was sustained virological response 12 weeks (SVR12) after first-line treatment and retreatment. Participants were factorially randomised to receive ribavirin with first-line treatment. Results: All evaluable participants achieved SVR12 overall (197/197, 100% [95% CI 98-100]) demonstrating non-inferiority between fixed-duration and variable-duration strategies (difference 0% [95% CI -3.8%, +3.7%], 4% pre-specified non-inferiority margin). First-line SVR12 was 91% [86%-97%] (92/101) for fixed-duration vs 48% [39%-57%] (47/98) for variable-duration, but was significantly higher for VUS2 (72% [56%-87%] (23/32)) than VUS1 (36% [25%-48%] (24/66)). Overall, first-line SVR12 was 72% [65%-78%] (70/101) without ribavirin and 68% [61%-76%] (69/98) with ribavirin (p=0.48). At treatment failure, the emergence of viral resistance was lower with ribavirin (12% [2%-30%] (3/26)) than without (38% [21%-58%] (11/29), p=0.01). Conclusions: Unsuccessful first-line short-course therapy did not compromise retreatment with sofosbuvir/ledipasvir/ribavirin (100% SVR12). SVR12 rates were significantly increased when ultrashort treatment varied between 4-7 weeks rather than 4-6 weeks. Ribavirin significantly reduced resistance emergence in those failing first-line therapy. ISRCTN Registration: 37915093 (11/04/2016).
Author(s): Cooke GS, Pett S, McCabe L, Jones C, Gilson R, Verma S, Ryder SD, Collier JD, Barclay ST, Ala A, Bhagani S, Nelson M, Ch'Ng C, Stone B, Wiselka M, Forton D, McPherson S, Halford R, Nguyen D, Smith D, Ansari A, Dennis E, Hudson F, Barnes EJ, Walker AS
Publication type: Article
Publication status: Published
Journal: Wellcome Open Research
Year: 2021
Volume: 6
Issue: 93
Online publication date: 29/07/2021
Acceptance date: 29/04/2021
Date deposited: 27/10/2023
ISSN (electronic): 2398-502X
Publisher: F1000 Research Ltd
URL: https://doi.org/10.12688/wellcomeopenres.16594.2
DOI: 10.12688/wellcomeopenres.16594.2
Data Access Statement: Underlying data Figshare: STOP-HCV-1 trial data. https://doi.org/10.6084/m9.figshare.14141411.v118 This project contains the following underlying data: - figsharedata.csv (Raw dataset containing baseline demographics, outcomes and VL results) Extended data Figshare: STOP-HCV-1 supplementary material. https://doi.org/10.6084/m9.figshare.14229212.v117 This project contains the following extended data: - STOP-HCV-1 supplementary material.docx (Supplementary methods and results) Reporting guidelines Figshare: CONSORT checklist for ‘Strategic treatment optimization for HCV (STOPHCV1): a randomised controlled trial of ultrashort duration therapy for chronic hepatitis C’. https://doi.org/10.6084/m9.figshare.14216063.v114 Data are available under the terms of the Creative Commons Zero “No rights reserved” data waiver (CC0 1.0 Public domain dedication).
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