Strategic treatment optimization for HCV (STOPHCV1): a randomised controlled trial of ultrashort duration therapy for chronic hepatitis C
<strong>Background:</strong> 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. <br> <strong>Methods:</strong> A total of 202 individuals...
| Κύριοι συγγραφείς: | , , , , , , , , , , , , , , , , , , , , , , , , |
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| Μορφή: | Journal article |
| Γλώσσα: | English |
| Έκδοση: |
F1000Research
2021
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| _version_ | 1826272939188682752 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Cooke, GS |
| collection | OXFORD |
| description | <strong>Background:</strong> 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.
<br>
<strong>Methods:</strong> 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.
<br>
<strong>Results:</strong> 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).
<br>
<strong>Conclusions:</strong> 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.
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<strong>ISRCTN Registration:</strong> 37915093 (11/04/2016). |
| first_indexed | 2024-03-06T22:20:28Z |
| format | Journal article |
| id | oxford-uuid:54df050a-a2a8-4b48-a511-601964277477 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T22:20:28Z |
| publishDate | 2021 |
| publisher | F1000Research |
| record_format | dspace |
| spelling | oxford-uuid:54df050a-a2a8-4b48-a511-6019642774772022-03-26T16:40:29ZStrategic treatment optimization for HCV (STOPHCV1): a randomised controlled trial of ultrashort duration therapy for chronic hepatitis CJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:54df050a-a2a8-4b48-a511-601964277477EnglishSymplectic ElementsF1000Research2021Cooke, GSPett, SMcCabe, LJones, CGilson, RVerma, SRyder, SDCollier, JDBarclay, STAla, ABhagani, SNelson, MCh'Ng, CStone, BWiselka, MForton, DMcPherson, SHalford, RNguyen, DSmith, DAnsari, ADennis, EHudson, FBarnes, EJWalker, AS<strong>Background:</strong> 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. <br> <strong>Methods:</strong> 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. <br> <strong>Results:</strong> 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). <br> <strong>Conclusions:</strong> 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. <br> <strong>ISRCTN Registration:</strong> 37915093 (11/04/2016). |
| spellingShingle | 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 Strategic treatment optimization for HCV (STOPHCV1): a randomised controlled trial of ultrashort duration therapy for chronic hepatitis C |
| title | Strategic treatment optimization for HCV (STOPHCV1): a randomised controlled trial of ultrashort duration therapy for chronic hepatitis C |
| title_full | Strategic treatment optimization for HCV (STOPHCV1): a randomised controlled trial of ultrashort duration therapy for chronic hepatitis C |
| title_fullStr | Strategic treatment optimization for HCV (STOPHCV1): a randomised controlled trial of ultrashort duration therapy for chronic hepatitis C |
| title_full_unstemmed | Strategic treatment optimization for HCV (STOPHCV1): a randomised controlled trial of ultrashort duration therapy for chronic hepatitis C |
| title_short | Strategic treatment optimization for HCV (STOPHCV1): a randomised controlled trial of ultrashort duration therapy for chronic hepatitis C |
| title_sort | strategic treatment optimization for hcv stophcv1 a randomised controlled trial of ultrashort duration therapy for chronic hepatitis c |
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