De Bruijne 2010a1

Methods	Randomised clinical trial
Participants	41 participants Sex: 31 men, 9 women Mean age: 48.8 years Inclusion criteria: 18‐65 years with BMI of 18‐40 kg/m2, HCV genotype 1 (any subtype), and HCV RNA level > 1 105 copies/mL (or equivalent international units). Chronic hepatitis C participants were naive, nonresponders or relapsers to previous IFN‐based treatment. Relapse was defined as undetectable HCV RNA upon completion of a previous IFN‐based treatment, but positive HCV RNA during follow‐up. Nonresponse was defined as positive HCV RNA at the end of a previous IFN‐based treatment or < 2‐log decline in HCV RNA levels at 12 weeks and discontinued treatment. Exclusion criteria: key exclusion criteria included decompensated liver disease, findings consistent with Child‐Pugh class B or C liver cirrhosis, and co‐infection with HIV or HBV.
Interventions	Experimental group: participants received either 800 mg narlaprevir 3 times daily or 400 mg narlaprevir as an oral suspension in combination with for 7 days in the first period and for 14 days in the second period. Control group: placebo. Co‐intervention: 200 mg ritonavir in cohort 3 and 4, a wash‐out period after 1 week of treatment, 1.5 lg/kg/week peg‐IFN‐α‐2b (in period 2) and standard care for 24 weeks after period 2.
Outcomes	Safety assessment, pharmacokinetic assessment, viral assessments.
Notes	Cohort 1 and 3 each included 10 participants naive to HCV treatment; cohorts 2 and 4 each included 10 HCV treatment‐experienced participants. We report here the treatment‐naive participants We contacted the trial authors on 26 February 2016 by email h.w.reesink@amc.nl about allocation concealment, how the blinding was maintained and who performed the outcome assessment; number of deaths, SAE, which group was the missing participants randomised to.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computer‐generated random code
Allocation concealment (selection bias)	Unclear risk	Not described
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	The study was described as double‐blinded but it was unclear how the blinding was maintained
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	Only 1 participant dropped out
Selective reporting (reporting bias)	Low risk	A protocol was found (NCT01081158) and the outcomes stated in the protocol were reported on
Vested‐interest bias	High risk	Sponsored by Schering‐Plough and designed by Schering‐Plough employees and HW Reesink
Other bias	Low risk	The trial appeared to be free of other components that could put it at risk of bias.