Fera 1993.

Study characteristics
Methods	Randomised, double‐blind, double‐dummy clinical trial
Participants	This trial assessed the effects of rifaximin versus placebo in 40 people with cirrhosis and chronic hepatic encephalopathy. There were 20 participants in each group. Age (mean ± SD) years Rifaximin group 60 ± 1.3 Lactulose group 58 ± 1.1 Proportion of men (n: %) Rifaximin group 15 (75) Lactulose group 14 (70) Aetiology of cirrhosis Not reported
Interventions	Intervention: 200 mg x 2 rifaximin plus 2 sachets of lactulose placebo (sorbitol) thrice daily for the first 14 days of each month for 90 days (n = 20) Control group: rifaximin placebo tablets x 2 and 2 sachets of lactulose (20 mg each) three times a day for the first 14 days of each month for 90 days (n = 20) Co‐interventions: magnesium sulphate (10 to 20 mg thrice daily) and evacuation enemas were performed if indicated. Duration of treatment: 3 times 14 days over a 90‐day period
Outcomes	Neuropsychiatric assessment PSE Sum/Index: mental state (West Haven Criteria); asterixis; cancelling A test; NCT‐A; EEG mean frequency; fasting blood ammonia
Inclusion period	Not reported
Outcomes included in meta‐analyses	Mortality, hepatic encephalopathy, adverse events, blood ammonia
Country of origin	Single centre in Italy
Notes	Publication status: full paper Vested interests bias: trial sponsored by Alpha‐Wassermann Additional information: individual participant data and details of randomisation methods were supplied by Alfa Wasserman. Authors contacted for further information on the aetiology of the participans' liver disease, confirmation of mortality outcomes, data on adverse events, and data regarding our secondary outcomes. Request sent on 5 April 2021; still awaiting response.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "..with randomised assignment of treatment." p. 59 in published report. Judgement: probably done
Allocation concealment (selection bias)	Low risk	Additional information from Alfa Wassermann: randomisation with list manually prepared by AW medical department. Central allocation and hence concealment
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Double‐dummy, double‐blind design
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Double‐dummy, double‐blind design
Incomplete outcome data (attrition bias) All outcomes	Low risk	No participants were withdrawn from the trial.
Selective reporting (reporting bias)	Low risk	All end points described are accounted for in the published report.
Other bias	Low risk	No other bias detected
Overall bias assessment (mortality)	Low risk	All domains at low risk of bias
Overall bias assessment (non‐mortality outcomes)	Low risk	All domains at low risk of bias