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Strategic treatment optimization for HCV (STOPHCV1): A randomised controlled trial of ultrashort duration therapy for chronic hepatitis C

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).

Publication metadata

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


DOI: 10.12688/wellcomeopenres.16594.2


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Funder referenceFunder name
MRC (MC_UU_12023/22)
NIHR (Project number 14/02/17)
Wellcome Trust
Wellcome Trust (090532/Z/09/Z)
Wellcome Trust [206296]