TY  - JOUR
AU  - Dore, GJ
AU  - Feld, JJ
AU  - Thompson, A
AU  - Martinello, M
AU  - Muir, AJ
AU  - Agarwal, K
AU  - Mullhaupt, B
AU  - Wedemeyer, H
AU  - Lacombe, K
AU  - Matthews, GV
AU  - Schultz, M
AU  - Klein, M
AU  - Hezode, C
AU  - Mercade, GE
AU  - Kho, D
AU  - Petoumenos, K
AU  - Marks, P
AU  - Tatsch, F
AU  - Dos Santos, AGP
AU  - Gane, E
AU  - Trinh, R
AU  - Erratt, A
AU  - Mercade, GE
AU  - Quiene, S
AU  - Shaw, I
AU  - Filep, E
AU  - Martinello, M
AU  - Petoumenos, K
AU  - Roberts, S
AU  - Foster, G
AU  - Curry, M
AU  - Warlow, J
AU  - Mauss, S
AU  - Stedman, C
AU  - Vachon, M-L
AU  - Christensen, S
AU  - Muir, A
AU  - Schultz, M
AU  - Baker, D
AU  - Ramji, A
AU  - Cornberg, M
AU  - Bloch, M
AU  - Hezode, C
AU  - Bourliere, M
AU  - Lacombe, K
AU  - Semmo, N
AU  - Agarwal, K
AU  - Cannon, M
AU  - Tam, E
AU  - Klein, M
AU  - Jacobson, I
AU  - Shaw, D
AU  - Levin, J
AU  - Tsoi, K
AU  - Cooke, G
AU  - Thompson, A
AU  - Matthews, G
AU  - Feld, J
AU  - Borgia, SM
AU  - Baumgarten, A
Y2  - 2020/12/14
Y1  - 2020/03/01
SN  - 0168-8278
UR  - http://hdl.handle.net/11343/253911
AB  - 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%).
LA  - English
PB  - ELSEVIER
T1  - Simplified monitoring for hepatitis C virus treatment with glecaprevir plus pibrentasvir, a randomised non-inferiority trial
DO  - 10.1016/j.jhep.2019.10.010
IS  - Journal of Hepatology
VL  - 72
IS  - 3
SP  - 431-440
ER  -