Mas 2003.

Study characteristics
Methods	Randomised, double‐blind, double‐dummy clinical trial
Participants	This trial assessed the effects of rifaximin versus lactitol in 103 people with cirrhosis and an acute episode of hepatic encephalopathy, grade I‐III. There were 50 participants in the rifaximin group and 53 in the placebo group. Age (mean ± SD) years Rifaximin 61.6 ± 9.7 Lactitol 62.9 ± 10.6 Proportion of men (n: %) Rifaximin 33 (70) Lactitol 39 (74) Aetiology of cirrhosis (n: %) Rifaximin Alcohol 25 (50) Posthepatitic 15 (30) Other 10 (20) Lactitol Alcohol 24 (45.3) Posthepatitic 22 (41.4) Other 7 (13.2)
Interventions	Intervention: rifaximin 2 x 200 mg and 20 gram placebo three times per day Control intervention: lactitol 20 gram and 2 tablets of placebo three times per day Co‐intervention: none Duration of treatment: 5 to 10 days
Outcomes	Neuropsychiatric assessment PSE Sum /Index: mental status (West Haven criteria), asterixis, NCT‐A, EEG mean frequency, blood ammonia
Inclusion period	November 1995 to December 1997
Outcomes included in meta‐analyses	Mortality, serious adverse effects, hepatic encephalopathy, non‐serious adverse effects, blood ammonia
Country of origin	A total of 13 investigatory sites in Spain
Notes	Publication status: full paper Vested interests bias: trial sponsored by Alpha ‐Wassermann. Additional information: individual participant data provided by Alpha‐Wassermann. The authors were contacted for further information on our secondary outcomes on 10 April 2021; 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: "Randomisation with computer‐generated list."
Allocation concealment (selection bias)	Low risk	All experimental material was divided into ‘patient‐units’ characterised by a label containing the previously assigned randomised number.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Double‐blind double‐dummy trial design
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote: "The statistical evaluation was performed by Clever Instruments (Barcelona, Spain) using a statistical package." p. 53 in published report. Judgement: outcome assessment performed by third‐party. Likely to have been blinded.
Incomplete outcome data (attrition bias) All outcomes	Low risk	All participants accounted for.
Selective reporting (reporting bias)	Low risk	All predetermined outcomes reported in full.
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.