HALLMARK‐DUAL 2014

Methods	Randomised clinical trial
Participants	307 adult participants Sex: 155 men, 152 women Mean age: 54.5 years Countries: Argentina, Australia, Austria, Canada, France, Germany, Ireland, Israel, Italy, Republic of Korea, Netherlands, New Zealand, Poland, Russian Federation, Spain, Taiwan, UK and USA. Inclusion criteria: aged at least 18 years with genotype 1b infection and HCV RNA of 10,000 IU/mL or greater who met inclusion criteria for 1 of 3 cohorts: treatment‐naive, previous non‐responder to peg‐IFNα plus RBV (null or partial response), or ineligible for, intolerant of, or ineligible for and intolerant of peg‐IFN α plus RBV (treatment‐naive and treatment‐experienced). Ineligible or intolerant (or both) participants included those with depression, anaemia or neutropenia, or compensated advanced fibrosis or cirrhosis (F3/F4) with thrombocytopaenia. Anaemia was defined as haemoglobin between 85 g/L and < 120 g/L (women) or < 130 g/L (men), neutropenia as absolute neutrophils between 0.5 x 10⁹ cells per L and < 1.5 x 10⁹ cells per L, and thrombocytopenia as platelets between 50 x 10⁹ cells per L and < 90 x 10⁹ cells per L, at screening or history of these conditions, while receiving peg‐IFN α plus RBV, or both. Exclusion criteria: people with HIV, ascites, oesophageal varices, or other evidence of hepatic decompensation.
Interventions	Experimental group: oral 60 mg once daily of daclatasvir and oral 100 mg twice daily of asunaprevir for 24 weeks. Control group: placebo for 12 weeks.
Outcomes	HCV RNA (SVR), safety assessment.
Notes	Only participants in the treatment‐naive group were randomised. The placebo group entered a new study after 12 weeks, therefore only data for the first 12 weeks could be used. We emailed Manns and colleagues on 27 April 2016 for additional information but reply not received yet.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computer‐generated random allocation sequence
Allocation concealment (selection bias)	Low risk	Interactive voice‐response system
Blinding of participants and personnel (performance bias) All outcomes	Low risk	The participants and personnel were blinded to treatment allocation until week 12, and we used data until week 12
Blinding of outcome assessment (detection bias) All outcomes	Low risk	The sponsors, who performed the analyses, were blinded until week 12, and we used data until week 12
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	The amount of drop‐outs until week 12 were not described
Selective reporting (reporting bias)	High risk	2 outcomes were added to the secondary outcomes in the protocol (NCT01581203)
Vested‐interest bias	High risk	The trial was funded by Bristol‐Myers Squibb
Other bias	Low risk	The trial appeared to be free of other components that could put it at risk of bias