FISSION 2013

Methods	Randomised, open label, active‐control study
Participants	527 participants were randomised and 499 participants were treated Sex: 327 men, 172 women Mean age: 48 years Inclusion criteria: eligible participants were treatment‐naive adults aged 18 years or older with chronic hepatitis C genotype 2 or 3 infection and HCV RNA above 10,000 IU/mL. Participants with Childs A cirrhosis were included. Exclusion criteria: BMI < 18 kg/m2; positive HbS‐Ab, positive HbC‐Ag, positive immunoglobulin‐M antibody, positive anti‐HIV antibody, history of other liver disease, current evidence of psychiatric illness, immunologic disorder, haemoglobinopathy, pulmonary disease (including pneumonia or pneumonitis), cardiac disease, seizure disorder or anticonvulsant use, poorly controlled diabetes, cancer, or history of malignancy, clinical signs and symptoms of acute pancreatitis with elevated lipase, clinically significant ECG findings at screening, history of major organ transplantation with an existing functional graft, active substance abuse, history of uncontrolled thyroid disease, haemoglobin < 11 g/dL for women or < 12 g/dL for men; neutrophil count < 1500 cells/nL, serum creatinine > 1.5 times the ULN, ALT or AST ≥ 10 x ULN, albumin ≤ 3.2 g/dL, total bilirubin 1.5 x ULN (except participants with Gilbert's syndrome).
Interventions	Experimental group 1: oral sofosbuvir 400 mg once daily for 12 weeks. Control group: peg‐IFN α‐2a subcutaneous once weekly 180 µg for 24 weeks. Co‐intervention: RBV 1000 mg/day (bodyweight < 75 kg) or 1200 mg/day (bodyweight ≥ 75 kg) for 12 or 24 weeks.
Outcomes	Proportion of participants with undetctable HCV RNA‐level at week 2 and week 4 under treatment, with SVR12, with SAE, AEs, mortality.
Notes	We emailed Lawitz and colleagues on 26 April 2016 for additional information but reply not received yet.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Centralised system
Allocation concealment (selection bias)	Unclear risk	Not reported
Blinding of participants and personnel (performance bias) All outcomes	High risk	Unblinded
Blinding of outcome assessment (detection bias) All outcomes	High risk	Unblinded
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	It was unclear how the trial handled participants with missing data
Selective reporting (reporting bias)	Low risk	All outcomes in the protocol were reported on
Vested‐interest bias	Unclear risk	The sponsor (Gilead) collected the data, monitored the conduct of the study, and performed the statistical analysis
Other bias	Low risk	The trial appeared to be free of other components that could put it at risk of bias