Dauphine 2015a1

Methods	Randomised, active‐controlled phase IIb trial
Participants	Sex: 260 men, 157 women Mean age: 48 years Inclusion criteria: eligible participants were treatment‐naive adults aged > 18 years with chronic HCV genotype 1 or 4 infection and HCV RNA above 50,000 IU/mL. Participants had to have evidence of chronic hepatitis C, documented by liver biopsy obtained within 24 months before randomisation. Exclusion criteria: participants with cirrhosis or incomplete/transition to cirrhosis (Knodell, Metavir, or Batts and Ludwig ≥ 3 or Ishak modified HAI ≥ 4); BMI < 18 or ≥ 36 kg/m2, other forms of liver disease; HIV infection; HCC; severe cardiac disease; severe depression or other psychiatric disease; renal disease; uncontrolled seizure disorders; severe retinopathy; haemoglobin < 12 g/dL for women or < 13 g/dL for men; neutrophil count < 90 cells/nL; serum creatinine > 1.5 times the ULN.
Interventions	Participants were randomised (2:2:2:2:1) to 1 of 5 treatment arms Experimental group 1: ritonavir boosted danoprevir (danoprevir/r) 200/100 mg twice a day for 24 weeks Experimental group 2: ritonavir boosted danoprevir (danoprevir/r) 100/100 mg twice a day for 24 weeks Experimental group 3: ritonavir boosted danoprevir (danoprevir/r) 50/100 mg twice a day for 24 weeks Experimental group 4: ritonavir boosted danoprevir (danoprevir/r) 100/100 mg twice a day for 12 weeks or 24 weeks (participants achieving undetectable HCV RNA from Weeks 2 to 10 (eRVR2) stopped treatment at Week 12) Control group: participants in Arm E with detectable HCV RNA at Week 12 had the option to roll over to treatment with danoprevir/r 200/100 mg twice a day Co‐intervention: peg‐IFN α‐2a (40KD) 180 lg/week and RBV 1000 mg/day (bodyweight < 75 kg) or 1200 mg/day (bodyweight ≥ 75 kg)
Outcomes	Proportion of participants with SVR24, with SAE, AEs, mortality.
Notes	Experimental group 1 vs Control.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computer‐generated randomisation
Allocation concealment (selection bias)	Unclear risk	Not described
Blinding of participants and personnel (performance bias) All outcomes	High risk	Unblinded
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Unblinded
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	There were above 5% dropouts and it was unclear how the trial handled the missing participants
Selective reporting (reporting bias)	Low risk	All outcomes stated in the protocol were reported on: NCT01220947
Vested‐interest bias	High risk	The trial was funded by F. Hoffmann‐La Roche Ltd
Other bias	Low risk	The trial appeared to be free of other components that could put it at risk of bias