Massa 1993.

Study characteristics
Methods	Randomised, double‐blind, double‐dummy clinical trial
Participants	This trial investigates the effects of rifaximin versus lactulose in 40 people with cirrhosis and chronic hepatic encephalopathy, grade I‐III. There were 20 participants in each group. Age (mean ± SD) years Rifaximin ‐ 54.1 ± 1.1 Lactulose ‐ 55.4 ± 1.1 Proportion of men (n: %) Rifaximin ‐ 13(65) Lactulose ‐ 14 (70) Aetiology of cirrhosis (n: %) Rifaximin group Alcohol 10 (50) Posthepatitic 10 (50) Lactulose group Alcohol 9 (45) Posthepatitic 11 (55)
Interventions	Intervention: rifaximin 200 mg x 2 plus 2 sachets of sorbitol 3 times per day Control intervention: placebo tablets x 2 plus 2 sachets of lactulose 10 g, 3 times per day Co‐intervention: none Duration of treatment: 15 days
Outcomes	Neuropsychiatric assessment PSE Sum/Index: Mental status (West Haven Criteria), asterixis, cancelling A test, NCT‐A, blood ammonia, EEG mean frequency
Inclusion period	Not reported
Outcomes included in meta‐analyses	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‐Wasserman. Additional information: individual participant data supplied by Alfa Wassermann. Authors contacted on 10 April 2021 for further information on the study inclusion period, blinding of outcome assessment, and data on both our primary and secondary analyses; still awaiting response.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Randomisation was carried out centrally using serially numbered, sealed, opaque envelopes stratified by the centre. Additional information from Alfa Wassermann: "Patients were randomised following a computer‐generated list."
Allocation concealment (selection bias)	Low risk	All experimental material was divided into ‘patient‐units’ characterized by a label containing the previously assigned randomised number.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote: "The patients received two tablets of placebo, externally indistinguishable from the rifaximin tablets administered to the previous group."
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Double‐blind, double‐dummy trial. Participants received either rifaximin plus sachets of sorbitol, indistinguishable from the lactulose sachets given to the other group, or placebo tablets, indistinguishable from the rifaximin tablets, and sachets of lactulose.
Incomplete outcome data (attrition bias) All outcomes	Low risk	All participants accounted for in published report.
Selective reporting (reporting bias)	Low risk	All end points reported in journal article.
Other bias	Low risk	No other bias detected.
Overall bias assessment (mortality)	Low risk	All bias categories are judged to be low risk.
Overall bias assessment (non‐mortality outcomes)	Low risk	All bias categories are judged to be low risk.