Title: Elbasvir plus grazoprevir in patients with hepatitis C virus infection and stage 4-5 chronic kidney disease: clinical, virological, and health-related quality-of-life outcomes from a phase 3, multicentre, randomised, double-blind, placebo-controlled trial

Bruchfeld, A. et al.


What You Need to Know:

In patients with chronic hepatitis C virus (HCV) infection and stage 4-5 chronic kidney disease, treatment with the fixed-dose combination of elbasvir plus grazoprevir over 12 weeks is effective with no major differences observed when administered immediately or when treatment was deferred.

Trial Design:

  • Multicenter, randomized, double-blind, placebo-controlled, phase 3 study analyzed sustained virological response (SVR), safety, health-related quality-of-life (HRQOL), and virological resistance in patients enrolled in the C-SURFER trial who received immediate antiviral therapy or placebo prior to therapy
  • C-SURFER study: observed high rates of virological cure in patients with HCV infection and stage 4-5 chronic kidney disease when treated with elbasvir plus grazoprevir regimen over 12 weeks
  • Patients received elbasvir 50mg + grazoprevir 100mg daily for 12 weeks (immediate treatment group) or placebo for 12 weeks then elbasvir 50mg + grazoprevir 100mg daily for 12 weeks starting at week 16 (deferred treatment group)
  • Primary endpoint: “safety and efficacy data for the treatment phase of the deferred treatment group, as well as HRQOL assessed using the 36-item Short Form Health Survey for all groups, and baseline and treatment-emergent resistance-associated substitutions (RASs)”
  • SVR at 12 weeks (SVR12): assessed in the modified full analysis set (FAS); included all patients except those who did not receive 1 study drug dose, died, or discontinued the study prior to the end of treatment due to reasons unrelated to HCV therapy

Key Outcomes:

  • Modified FAS: 116 patients in immediate treatment group, 99 in deferred treatment group
  • 99.1% of immediate treatment patients (115/116 patients; 95% CI: 95.3, 100.0) attained SVR12 vs 98.0% of deferred treatment patients (97/99 patients; 95% CI: 92.9, 99.7)
  • Patients with genotype 1a infections: “SVR12 was achieved by 11 (84.6%) of 13 patients with detectable baseline NS5A RASs and in 98% (100%) of 98 without”
  • No difference in HRQOL between groups observed at week 12
  • Serious adverse events (both deemed related to study drug): 1 case of interstitial nephritis occurred during deferred treatment, 1 case of raised lipase concentration occurred during placebo phase
  • 4 deaths occurred (all deemed unrelated to study drugs): 1 in immediate treatment group, 3 in deferred treatment group
  • No differences in aminotransferase elevations observed between groups; no total bilirubin elevations observed in deferred treatment group