STARTverso‐3 2013a1

Methods	Randomised clinical trial
Participants	678 participants Sex: 403 men, 274 women Mean age: 53.4 years Inclusion criteria: chronic hepatitis C genotype 1 infection, diagnosed at least 6 months prior to screening, confirmed prior virological failure with an approved dose of peg‐IFN/RBV age 18‐70 years, HCV RNA = 1000 IU/mL at screening. Exclusion criteria: HCV infection of mixed genotype; HBV or HIV co‐infection. Evidence of acute or chronic liver disease due to causes other than chronic HCV infection, decompensated liver disease, or history of decompensated liver disease. Body weight < 40 or > 125 kg, clinical evidence of significant or unstable cardiovascular disease, chronic pulmonary disease, history or evidence of retinopathy or clinically significant ophthalmological disorder. Pre‐existing psychiatric condition that could interfere with the participant's participation in and completion of the study, laboratory parameters disorders (thalassaemia major, sickle cell anaemia or G6PD deficit). Haemoglobin < 12 g/dL for women and < 13 g/dL for men, participants who had been previously treated with at least 1 dose of any antiviral or immunomodulatory drug other than IFN alfa or RBV for acute or chronic HCV infection including and not restricted to protease or polymerase inhibitors.
Interventions	The trial was divided into 3 cohorts according to virological failure (relapse, partial, null response) and randomised to 1 of the following groups: Experimental group 1: participants received faldaprevir 240 mg once daily, in the form of 2 soft gelatin capsules administered orally, combined with peg‐IFN/RBV, administered by injection, for 12 weeks, followed by placebo once daily combined with peg‐IFN/RBV for 12 weeks Experimental group 2: participants received faldaprevir 240mg once daily, in the form of 2 soft gelatin capsules administered orally, combined with peg‐IFN/RBV, administered by injection, for 24 weeks. Control group: received 2 soft gelatin capsules identical to those containing faldaprevir once daily (orally) and peg‐IFN α‐2a/RBV) administered by injection, for 24 weeks. Co‐intervention: At week 24, if the participants did not achieve early treatment success the participants received an additional 24 weeks of peg‐IFN/RBV alone.
Outcomes	SVR, early treatment success, AST, ALT normalisation, safety.
Notes	We emailed Jacobson and colleagues on 26 April 2016 for additional information on primary publication, randomisation, blinding, all bias, death but reply not received yet.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Not described
Allocation concealment (selection bias)	Unclear risk	Not described
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	The trial was described as being blinded but method was not described
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	The trial was described as being blinded but method was not described
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	More than 5% dropped out and the trial did not report how they dealt with missing data
Selective reporting (reporting bias)	High risk	The trial changed the primary outcomes from the original version (NCT01358864 )
Vested‐interest bias	High risk	The trial was funded by Boehringer Ingelheim
Other bias	Low risk	The trial appeared to be free of other components that could put it at risk of bias