Rodriguez‐Torres 2013

Methods	Randomised clinical trial
Participants	64 participants Sex: 43 men, 20 women Mean age: 45.1 years Inclusion criteria: 64 treatment‐naive participants with chronic HCV genotype 1 infection were enrolled (HCV RNA levels P100,000 IU/mL at screening), 18–65 years of age with a BMI of 18–36 kg/m2. Women of childbearing potential were required to use a protocol‐approved method of contraception. 1 participant in the sofosbuvir 200 mg arm withdrew consent before receiving the first dose of study medication. Exclusion criteria: a liver biopsy within 3 years of dosing was required to exclude cirrhosis. Participants were otherwise in good health, with no significant co‐morbidities. Other key exclusion criteria included positive test for hepatitis B surface antigen, anti‐hepatitis B core protein IgM antibodies and anti‐HIV antibodies. Randomization was stratified by interleukin(IL) 28B status (rs12979860) for CC or CT/TT allele.
Interventions	Participants were randomised in a ratio of active:placebo of 1:1:1:1 Experimental group: participants received 1 of 3 once‐daily doses of sofosbuvir (100 mg, 200 mg, or 400 mg). Control group: placebo plus peg‐IFN α‐2a/RBV for 28 days. Co‐intervention: peg‐IFN α‐2a and RBV were administered according to the package insert for participants with genotype 1 infection. After end of treatment, participants continued treatment with peg‐IFN α‐2a/RBV alone for a further 44 weeks.
Outcomes	Primary outcome: AEs. Secondary outcomes: change in circulating HCV RNA at Week 4, percentage of participants with RVR at Week 4, percentage of participants with SVR at 12 and 24 weeks after last dose of peg+RBV following completion of 48 weeks of treatment, pharmacokinetics, percentage of participants who developed resistance to sofosbuvir.
Notes	We emailed Rodriguez‐Torres and colleagues on 27 April 2016 for additional information on blinding during assessment, unpublished data, (mortality data) but reply not received yet.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	The randomisation schedule was provided by PharStat, Inc. (NC, USA)
Allocation concealment (selection bias)	Low risk	Participants were randomised by a central web‐based system using permutated blocks
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Both investigators and participants were blinded to the treatment assignment
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	The study was described as double‐blinded but it was unclear how the blinding was maintained and who performed the outcome assessment
Incomplete outcome data (attrition bias) All outcomes	Low risk	2 participants dropped out during study
Selective reporting (reporting bias)	Low risk	A protocol was found (NCT01054729) and all outcomes reported on
Vested‐interest bias	High risk	This study was funded by Gilead Sciences, Inc.
Other bias	Low risk	The trial appeared to be free of other components that could put it at risk of bias