POSITRON 2013

Methods	Blinded placebo‐controlled trial (NCT01542788)
Participants	Randomised: 280 underwent randomisation, and 278 began treatment Experimental group: 209 randomised, 207 treated Control group: 71 randomised, 71 treated Sex: 151 men, 127 women Mean age: 52 years Countries: 63 sites in the USA, Canada, Australia, and New Zealand from March 2012‐May 2012. Inclusion criteria: eligible participants were cirrhotic or non‐cirrhotic adults with HCV genotype 2 or 3 infection, a baseline HCV RNA level > 10,000 IU/mL unwilling or uneligible or intolerant for IFN‐treatment. Participants had chronic hepatitis C infection (documented by positive anti‐HCV antibody test or positive HCV RNA, or positive HCV genotyping test ≥ 6 months prior to the Baseline/Day 1 visit; or documented by liver biopsy performed prior to the Baseline/Day 1 visit with evidence of chronic HCV). Participants had a BMI > = 18 kg/m2, a screening ECG without clinically significant abnormalities, no evidence of HCC, no Chronic liver disease of a non‐HCV aetiology (e.g. hemochromatosis, Wilson’s disease, α1‐antitrypsin deficiency, and cholangitis) and no co‐infection with HBV or HIV. Participants had no history of significant pulmonary or cardiac disease, or porphyria; no current or prior history of clinical hepatic decompensation (e.g. ascites, jaundice, encephalopathy, or variceal haemorrhage).
Interventions	Randomisation was performed centrally in a 3:1 ratio with stratification according to the presence or absence of cirrhosis. Experimental group: oral sofosbuvir 400 mg once daily + RBV (1000 mg daily in participants with a body weight < 75 kg, and 1200 mg daily in participants with a body weight ≥ 75 kg) for 12 weeks. Control group: placebo.
Outcomes	Proportion of participants with end‐of‐treatment response (week12), SVR12, SAE, AEs, mortality.
Notes	We emailed Jacobson and colleagues on 21 April 2016 for additional information on generation of allocation sequence, how many participants dropped out and how the trial handled missing data but reply not received yet.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Not reported
Allocation concealment (selection bias)	Low risk	"An Interactive Web Response System (IWRS) will be employed to manage participant randomization and study drug assignment."
Blinding of participants and personnel (performance bias) All outcomes	Low risk	The participant, caregiver, investigator, outcomes assessor were described as being blinded and the placebo was identical in appearance
Blinding of outcome assessment (detection bias) All outcomes	Low risk	The participant, caregiver, investigator, outcomes assessor were described as being blinded and the placebo was identical in appearance
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	It was unclear how many participants dropped out and how the trial handled missing data
Selective reporting (reporting bias)	Low risk	The outcomes stated in the protocol were reported on
Vested‐interest bias	High risk	The sponsor collected the data, monitored study conduct, 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