Ledipasvir and Sofosbuvir Plus Ribavirin for Treatment of HCV Infection in Patients With Advanced Liver Disease.
Charlton M, Everson GT, et al.Gastroenterology 2015; 149(3): 649-659.
Aims
To determine the efficacy and safety of ledipasvir-sofosbuvir with ribavirin in patients with advanced liver disease, include those undergone liver transplantation.
Interventions
Patients were randomized into seven groups and received either 12 or 24 weeks of treatment with ledipasvir 90 mg and sofosbuvir 400 mg in a fixed-dose combination tablet (ledipasvir sofosbuvir) once daily plus ribavirin. For groups 3, 4, and 7, ribavirin was administered orally twice daily, with the dose determined according to body weight . For groups 1, 2, 5, and 6, ribavirin was administered at a starting dose of 600mg in a divided daily dose.
Participants
337 patients ≥ 18 years of age and chronically infected with genotypes 1 or 4 chronic hepatitis C virus (HCV).
Outcomes
The primary outcomes measured were the rate of sustained virologic response and the proportion of patients who discontinued study treatment owing to an adverse event. Secondary outcomes included improvements in Child–Pugh class and model for end-stage liver disease (MELD) score.The efficacy outcome for patients who underwent liver transplantation was the rate of post-transplant virologic response.
Follow-up
12 weeks
CET Conclusions
This large multicentre industry-led study investigates the use of ledipasvir and sofosbuvir, in addition to ribavirin, in patients with HCV infection and advanced liver disease both pre and post-transplant. Post-transplant patients enrolled were stratified by the degree of cirrhosis and each group randomised to 12 or 24 weeks of treatment. The combination produced high rates of sustained virological response in all groups, with no difference seen between 12 and 24 weeks of treatment. These results are impressive and provide a treatment option for a group of patients previously difficult to manage. The main downside to the study is the lack of a control arm undergoing current standard of care. Indeed, no power calculation was performed and the results are presented with rather imprecise 90% confidence intervals, leading one to question what value randomisation has offered over a simple cohort study in this case.
Data analysis
Modified intention-to-treat analysis
Trial registration
ClinicalTrials.gov - NCT01938430