Bajaj 2019.

Study characteristics
Methods	Two randomised trials, from which data were pooled. Trial 1: randomised, phase 3, double‐blind trial Trial 2: randomised, phase 4, open‐label trial
Participants	These trials assessed the effect of rifaximin (± lactulose) versus lactulose (permitted in trial 1, mandatory in trial 2) (+ placebo) for the secondary prevention of hepatic encephalopathy in people with cirrhosis who had experienced an episode of acute hepatic encephalopathy in the preceding 6 months but currently had a West Haven score of 1 or less Rifaximin plus lactulose (n = 236); lactulose (plus placebo) alone (n = 145) Age (mean) years Rifaximin plus lactulose 56.9 Placebo plus lactulose 56.6 Proportion of men (n: %) Rifaximin plus lactulose 139 (58.9) Placebo plus lactulose 85 (68.3) Aetiology of cirrhosis: not reported Participants in complete remission at baseline ( %) Rifaximin plus lactulose 67.4 Placebo plus lactulose 67.6
Interventions	Intervention: Trial 1: rifaximin 550 mg twice daily with or without concurrent lactulose, titrated to produce 2 to 3 semi‐soft stools per day Trial 2: rifaximin 550 mg twice daily with concurrent lactulose, titrated to produce 2 to 3 soft stools per day Control interventions: Trial 1: placebo with or without concurrent lactulose, titrated to produce 2 to 3 semi‐soft stools per day Trial 2: lactulose, titrated to produce 2 to 3 semi‐soft stools per day Co‐interventions: not reported Duration of therapy: not specifically reported ‐ up to 6 months
Outcomes	Neuropsychiatric assessment Mental status: West Haven criteria Breakthrough episode of hepatic encephalopathy defined as West Haven criteria score of 2 or more
Inclusion period	Not reported
Outcomes included in meta‐analyses	Mortality, serious adverse events (hospitalisation), hepatic encephalopathy, adverse events
Country of origin	Unknown
Notes	Publication status: abstract only Vested interests bias: no conflicts of interest were declared Additional information: authors contacted for further information on study centres, co‐interventions used, participant characteristics, trial registration status, country of origin, conflicts of interest, randomisation and blinding methods, complete outcome reporting, and whether the data from the two pooled studies could be split to allow further analyses. The request was sent on 3 April 2021; still awaiting response.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	The authors report randomisation, but have not stated how this was conducted.
Allocation concealment (selection bias)	Unclear risk	No information provided by the authors
Blinding of participants and personnel (performance bias) All outcomes	High risk	Trial 1 was double‐blind ‐ although the methods of blinding are not reported by the authors. Trial 2 was open‐label, which introduces bias.
Blinding of outcome assessment (detection bias) All outcomes	High risk	Trial 1 was double‐blind ‐ although the methods of blinding are not reported by the authors. Trial 2 was open‐label, which introduces bias.
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Not reported by the authors
Selective reporting (reporting bias)	Unclear risk	We did not have access to a protocol or trial registry to assess whether all outcomes were reported.
Other bias	Low risk	No other bias identified
Overall bias assessment (mortality)	Unclear risk	One or more domains was deemed 'unclear risk' of bias.
Overall bias assessment (non‐mortality outcomes)	High risk	High risk of performance and detection bias