ATLAS 2013

Methods	Randomised phase II clinical trial
Participants	225 participants Inclusion criteria: HCV treatment‐naïve adults aged 18 years or older with serologic evidence of chronic HCV genotype 1 infection, a serum HCV RNA level 50,000 IU/mL, and an absence of advanced fibrosis or cirrhosis (METAVIR score of F3‐4). Exclusion criteria: participants infected with HCV non‐1 genotypes or co‐infected with HBV or with HIV were excluded, as were participants with liver disease attributable to a cause other than HCV infection, cardiac or renal disease, severe psychiatric disease, uncontrolled seizures, severe retinopathy, immunologically‐mediated disease, poorly controlled diabetes, or who were pregnant or breastfeeding. Participants were also excluded if they had a haemoglobin concentration < 11 g/dL (women), or < 12 g/dL (men); neutrophil count < 1.5 x 109 cells/L; platelet count < 90 x 109 cells/L; serum creatinine concentration > 1.5 times the ULN); or BMI (calculated as kg/m2) < 18 or > 36. The use of agents that could interfere with the metabolism of danoprevir was prohibited.
Interventions	Experimental group: dareprevir (orally at a dose of 300 mg every 8 h) and peg‐IFN α‐2a (by subcutaneous injection at a dose of 180 μg per week) and RBV (orally at a dose of 1000 mg per day (in participants who weighed < 75 kg) or 1200 mg per day (in participants who weighed ≥ 75 kg)) for the entire 12 weeks dareprevir (orally at a dose of 600 mg every 12 hours) and peg‐IFN α‐2a (by subcutaneous injection at a dose of 180 μg per week) and RBV (orally at a dose of 1000 mg per day (in participants who weighed < 75 kg) or 1200 mg per day (in participants who weighed ≥ 75 kg)) for the entire 12 weeks dareprevir (orally at a dose of 900 mg every 12 h) and peg‐IFN α‐2a (by subcutaneous injection at a dose of 180 μg per week) and RBV (orally at a dose of 1000 mg per day (in participants who weighed < 75 kg) or 1200 mg per day (in participants who weighed ≥ 75 kg or more)) for the entire 12 weeks Control group: placebo with peg‐IFN–RBV for 24 or 48 weeks Co‐intervention: peg‐IFN (subcutaneously at 180 µg/week) and RBV orally twice daily dosed according to body weight
Outcomes	HCV RNA (SVR), safety assessment
Notes	we emailed Marcellin 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 randomisation code
Allocation concealment (selection bias)	Low risk	Interactive voice/web response system
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	The trial was described as "partial‐blind labeling"
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	The trial was described as being double‐blinded but it was unclear how the blinding was performed
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	More than 5% dropped out
Selective reporting (reporting bias)	Low risk	All outcomes stated in the protocol were assessed (NCT00963885)
Vested‐interest bias	High risk	The trial was funded by Bristol‐Myers Squibb
Other bias	Low risk	The trial appeared to be free of other components that could put it at risk of bias