Simplified monitoring for hepatitis C virus treatment with glecaprevir plus pibrentasvir, a randomised non-inferiority trial.
Journal Article (Clinical Trial, Phase III;Journal Article;Multicenter Study)
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%).
- Dore, GJ; Feld, JJ; Thompson, A; Martinello, M; Muir, AJ; Agarwal, K; Müllhaupt, B; Wedemeyer, H; Lacombe, K; Matthews, GV; Schultz, M; Klein, M; Hezode, C; Mercade, GE; Kho, D; Petoumenos, K; Marks, P; Tatsch, F; Dos Santos, AGP; Gane, E; SMART-C Study Group,
- March 2020
Volume / Issue
- 72 / 3
Start / End Page
- 431 - 440
Electronic International Standard Serial Number (EISSN)
Digital Object Identifier (DOI)