Gregory J Dore1, Jordan J Feld2, Alex Thompson3, Marianne Martinello4, Andrew J Muir5, Kosh Agarwal6, Beat Müllhaupt7, Heiner Wedemeyer8, Karine Lacombe9, Gail V Matthews10, Michael Schultz11, Marina Klein12, Christophe Hezode13, Gerard Estivill Mercade4, Danny Kho4, Kathy Petoumenos4, Philippa Marks4, Fernando Tatsch14, Ana Gabriela Pires Dos Santos14, Ed Gane15. 1. Kirby Institute, UNSW Sydney, Sydney, Australia; St Vincent's Hospital, Sydney, Australia. Electronic address: gdore@kirby.unsw.edu.au. 2. Toronto Centre for Liver Disease, Toronto General Hospital, Toronto, Canada. 3. St Vincent's Hospital, Melbourne, Australia; University of Melbourne, Melbourne, Australia. 4. Kirby Institute, UNSW Sydney, Sydney, Australia. 5. Duke University School of Medicine, Durham, United States. 6. Institute of Liver Studies, King's College Hospital, London, United Kingdom. 7. University Hospital, Zürich, Switzerland. 8. University Clinic Essen, Essen, Germany. 9. Sorbonne Université, IPLESP, Saint-Antoine Hospital, AP-HP, Paris, France. 10. Kirby Institute, UNSW Sydney, Sydney, Australia; St Vincent's Hospital, Sydney, Australia. 11. Dunedin Hospital, Dunedin, New Zealand. 12. McGill University Health Centre, Montreal, Canada. 13. University of Paris-Est, INSERM U955, Henri Mondor Hospital, AP-HP, Creteil, France. 14. Abbvie Inc., North Chicago, IL, United States. 15. Auckland Hospital, Auckland, New Zealand.
Abstract
BACKGROUND & AIMS:Direct-acting antiviral (DAA) therapy for HCV has high efficacy and limited toxicity. We hypothesised that the efficacy of glecaprevir-pibrentasvir for chronic HCV with a simplified treatment monitoring schedule would be non-inferior to a standard treatment monitoring schedule. METHODS: In this open-label multicentre phase IIIb trial, treatment-naïve adults with chronic HCV without cirrhosis were randomly assigned (2:1) to receive glecaprevir-pibrentasvir 300 mg-120 mg daily for 8 weeks administered with a simplified or standard monitoring strategy. Clinic visits occurred at baseline and post-treatment week 12 in the simplified arm, and at baseline, week 4, week 8, and post-treatment week 12 in the standard arm. Study nurse phone contact occurred at week 4 and week 8 in both arms. Participants requiring adherence support were not eligible, including those reporting recent injecting drug use. The primary endpoint was sustained virological response at post-treatment week 12 (SVR12), with a non-inferiority margin of 6%. RESULTS: Overall, 380 participants (60% male, 47% genotype 1, 32% genotype 3) with chronic HCV were randomised and treated with glecaprevir-pibrentasvir in the simplified (n = 253) and standard (n = 127) arms. In the intention-to-treat population, SVR12 was 92% (95% CI 89%-95%) in the simplified and 95% (95% CI 92%-99%) in the standard arm (difference between arms -3.2%; 95% CI -8.2% to 1.8%) and did not reach non-inferiority. In the per-protocol population, SVR12 was 97% (95% CI 96%-99%) in the simplified and 98% (95% CI 96%-100%) in the standard arm. No treatment-related serious adverse events were reported. CONCLUSIONS: In patients with chronic HCV infection without cirrhosis, treatment withglecaprevir-pibrentasvir was safe and effective. In comparison to standard monitoring, a simplified monitoring schedule did not achieve non-inferiority. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT03117569. LAY SUMMARY:Direct-acting antiviral (DAA) therapy for hepatitis C is highly effective and well tolerated. The SMART-C randomised trial evaluated an 8-week regimen of glecaprevir-pibrentasvir for hepatitis C treatment, using a simplified monitoring schedule that included no pathology tests or clinic visits during treatment. This simplified strategy produced a high cure rate (92%), but this was not equivalent to the standard monitoring schedule cure rate (95%).
RCT Entities:
BACKGROUND & AIMS: Direct-acting antiviral (DAA) therapy for HCV has high efficacy and limited toxicity. We hypothesised that the efficacy of glecaprevir-pibrentasvir for chronic HCV with a simplified treatment monitoring schedule would be non-inferior to a standard treatment monitoring schedule. METHODS: In this open-label multicentre phase IIIb trial, treatment-naïve adults with chronic HCV without cirrhosis were randomly assigned (2:1) to receive glecaprevir-pibrentasvir 300 mg-120 mg daily for 8 weeks administered with a simplified or standard monitoring strategy. Clinic visits occurred at baseline and post-treatment week 12 in the simplified arm, and at baseline, week 4, week 8, and post-treatment week 12 in the standard arm. Study nurse phone contact occurred at week 4 and week 8 in both arms. Participants requiring adherence support were not eligible, including those reporting recent injecting drug use. The primary endpoint was sustained virological response at post-treatment week 12 (SVR12), with a non-inferiority margin of 6%. RESULTS: Overall, 380 participants (60% male, 47% genotype 1, 32% genotype 3) with chronic HCV were randomised and treated with glecaprevir-pibrentasvir in the simplified (n = 253) and standard (n = 127) arms. In the intention-to-treat population, SVR12 was 92% (95% CI 89%-95%) in the simplified and 95% (95% CI 92%-99%) in the standard arm (difference between arms -3.2%; 95% CI -8.2% to 1.8%) and did not reach non-inferiority. In the per-protocol population, SVR12 was 97% (95% CI 96%-99%) in the simplified and 98% (95% CI 96%-100%) in the standard arm. No treatment-related serious adverse events were reported. CONCLUSIONS: In patients with chronic HCV infection without cirrhosis, treatment with glecaprevir-pibrentasvir was safe and effective. In comparison to standard monitoring, a simplified monitoring schedule did not achieve non-inferiority. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT03117569. LAY SUMMARY: Direct-acting antiviral (DAA) therapy for hepatitis C is highly effective and well tolerated. The SMART-C randomised trial evaluated an 8-week regimen of glecaprevir-pibrentasvir for hepatitis C treatment, using a simplified monitoring schedule that included no pathology tests or clinic visits during treatment. This simplified strategy produced a high cure rate (92%), but this was not equivalent to the standard monitoring schedule cure rate (95%).
Authors: Sunil S Solomon; Sandra Wagner-Cardoso; Laura Smeaton; Leonard A Sowah; Chanelle Wimbish; Gregory Robbins; Irena Brates; Christine Scello; Annie Son; Anchalee Avihingsanon; Benjamin Linas; Donald Anthony; Estevão Portela Nunes; Dimas A Kliemann; Khuanchai Supparatpinyo; Cissy Kityo; Pablo Tebas; Jaclyn Ann Bennet; Jorge Santana-Bagur; Constance A Benson; Marije Van Schalkwyk; Nelson Cheinquer; Susanna Naggie; David Wyles; Mark Sulkowski Journal: Lancet Gastroenterol Hepatol Date: 2022-01-10
Authors: J S Davis; M Young; C Marshall; J Tate-Baker; M Madison; S Sharma; C Silva; T Jones; J Davies Journal: Open Forum Infect Dis Date: 2020-01-19 Impact factor: 3.835