C‐EDGE TN 2015

Methods	Randomised clinical trial
Participants	421 participants Sex: 227 men, 194 women Mean age: 52.6 years Countries: Australia, Czech Republic, France, Germany, Israel, Puerto Rico, South Korea, Sweden, Taiwan, and USA Inclusion criteria: treatment‐naive cirrhotic and non‐cirrhotic adults (aged > 18 years) with HCV RNA levels > 104 IU/mL were eligible. Hepatic fibrosis was staged by biopsy or noninvasive assessment. Exclusion criteria: decompensated liver disease, HCC, HIV or HBV co‐infection, uncontrolled diabetes mellitus (haemoglobin A1c level > 10%), elevated prothrombin time unrelated to anticoagulation, creatinine clearance < 50 mL/min, haemoglobin level < 95 g/L, thrombocytopenia (platelet count < 50 × 109 cells/L), aminotransferase levels more than 10 times the ULN, or hypoalbuminaemia (albumin level < 30 g/L).
Interventions	Experimental group: oral 100 mg of grazoprevir and 50 mg of elbasvir for 12 weeks. Control group: placebo.
Outcomes	HCV RNA, safety assessment.
Notes	Only data for the first 12 weeks could be used, since the control group received the same DAA in the following 12 weeks. We emailed Zeuzem and colleagues on 27 April 2016 for additional information but reply not received yet.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	The trial used a "computer‐generated random allocation schedule"
Allocation concealment (selection bias)	Low risk	The trial used a "central interactive voice‐response system"
Blinding of participants and personnel (performance bias) All outcomes	Low risk	The participants and personnel were blinded to treatment assignment for the first 12 weeks (and we used the data from this time point)
Blinding of outcome assessment (detection bias) All outcomes	Low risk	The sponsors performing the analyses were blinded to treatment assignment for the first 12 weeks (and we used the data from this time point)
Incomplete outcome data (attrition bias) All outcomes	Low risk	< 5% dropped out after 12 weeks
Selective reporting (reporting bias)	Low risk	All outcomes stated in the protocol were assessed (NC02105467)
Vested‐interest bias	High risk	The trial was funded by Merck‐Sharp which performed the analyses
Other bias	Low risk	Trial seems to be free of other potential sources of bias