Festi 1993.

Study characteristics
Methods	Randomised, open‐label clinical trial
Participants	This trial assessed the effects of rifaximin versus lactulose in 201 participants with cirrhosis and chronic hepatic encephalopathy grade 1. A total of 136 participants were eventually included in the study. Three studies were undertaken:* 1) Open study of rifaximin (80 participants received rifaximin) 2) Randomised clinical trial of rifaximin (n = 20) versus neomycin (n = 15) 3) Randomised clinical trial of rifaximin (n = 9) versus lactulose (n = 12) *Only the comparison between rifaximin and lactulose was assessed Age (mean) years Rifaximin 59 Lactulose 60.9 Proportion of men (n: %) Rifaximin 9 (100) Lactulose 8 (66.6) Aetiology of cirrhosis (total group) (n: %) Alcoholic 43 (32) Hepatitis 45 (33) Cryptogenic 48 (35)
Interventions	Intervention: rifaximin 1200 mg daily Control intervention: lactulose 40 mg daily Co‐intervention: none Duration of treatment: 21 days
Outcomes	Neuropsychiatric assessment PSE Sum/Index: Mental status (West Haven criteria), asterixis, NCT‐A, EEG mean frequency; blood ammonia
Inclusion period	1988 to 1991
Outcomes included in meta‐analyses	Mortality, hepatic encephalopathy, adverse events, blood ammonia
Country of origin	A total of 10 investigatory centres in Italy
Notes	Publication status : full paper Vested interests bias: trial sponsored by Alpha ‐Wassermann Additional information: individual participant data and information on primary end points and randomisation provided by Alfa Wassermann Alfasigma contacted on 5 April 2021 for further information on blinding status, concealment of allocation, handling of missing data, mortality, adverse events for the randomised clinical trial arm, and data on secondary outcomes; still awaiting response.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "Patients were assigned to rifaximin or lactulose in a randomised fashion." p. 600 in published report. Additional information from Alfa Wassermann: "Open comparative study design. Randomisation was done as subsequent patients in the office (pair/unpair). The investigators allocated participants based on an open table of random numbers".
Allocation concealment (selection bias)	Unclear risk	No information provided on allocation concealment.
Blinding of participants and personnel (performance bias) All outcomes	High risk	No blinding of participants or personnel
Blinding of outcome assessment (detection bias) All outcomes	High risk	No information on blinding of outcome assessors but highly unlikely
Incomplete outcome data (attrition bias) All outcomes	High risk	No information on participants withdrawn from the trial. No information on the number of participants completing the trial.
Selective reporting (reporting bias)	Low risk	No selective reporting
Other bias	Low risk	No other bias detected
Overall bias assessment (mortality)	High risk	High risk of selection bias, attrition bias and detection performance
Overall bias assessment (non‐mortality outcomes)	High risk	High risk of selection, attrition bias and detection performance