Pawar 2019.

Study characteristics
Methods	Randomised, three‐way, double‐blind clinical trial
Participants	This trial assessed the effects of rifaximin versus placebo and rifaximin versus lactulose in 108 people with cirrhosis and minimal hepatic encephalopathy. There were 37 participants in the rifaximin and lactulose groups and 36 in the placebo group. Age (mean ± SD) years Rifaximin 48.8 ± 7.0 Lactulose 48.4 ± 8.2 Placebo 48.7 ± 7.2 Proportion of men (n: %) Rifaximin 34 (91.8) Lactulose 31 (88.6) Placebo 33 (91.7) Aetiology of cirrhosis ( n: %) Rifaximin Alcohol ‐ 20 (54.1) NASH ‐ 3 (8.1) Hepatitis B ‐ 4 (10.8) Hepatitis C ‐ 2 (5.4) Autoimmune hepatitis ‐ 1 (2.7) Budd Chiari syndrome ‐1 (2.7) Lactulose Alcohol ‐ 21 (56.8) NASH ‐ 5 (13.5) Hepatitis B ‐ 7 (18.9) Hepatitis C ‐ 3 (8.1) Autoimmune hepatitis ‐ 1 (2.7) Budd Chiari syndrome ‐ 0 (0.0) Placebo Alcohol ‐ 22 (61.1) NASH ‐ 5 (13.9) Hepatitis B ‐ 7 (19.4) Hepatitis C ‐ 3 (8.3) Autoimmune hepatitis ‐ 2 (5.6) Budd Chiari syndrome ‐1 (2.8)
Interventions	Treatment 1: rifaximin 550 mg twice daily: unclear if a lactulose placebo was used Treatment 2: lactulose 30 to 60 ml/day titrated to produce 2 semi‐soft stools/day: unclear if a placebo rifaximin was used. Control: 'placebo' vitamin B‐complex tablets twice daily Treatment duration: 3 months
Outcomes	Neuropsychiatric assessment Minimal hepatic encephalopathy was diagnosed based on a Psychometric Hepatic Encephalopathy Score (PHES) of ≤ ‐5 and/or Inhibitory Control Test lures ≥ 14 Reversal of minimal hepatic encephalopathy was defined as Psychometric Hepatic Encephalopathy Score ≥ ‐5 and or Inhibitory Control Test lures ≤ 14
Inclusion period	May 2015 to March 2017
Outcomes included in meta‐analyses	Rifaximin versus placebo and rifaximin versus placebo considered separately Hepatic encephalopathy, adverse events
Country of origin	Single centre in India
Notes	Publication status: full paper Vested interests bias: none declared Additional information: authors contacted for further information on 14 September 2021 regarding whether the abstract Pawar 2016 included the same participant cohort as Pawar 2019; still awaiting response.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Participants were randomised by an independent observer using a computer‐generated list of random numbers.
Allocation concealment (selection bias)	Low risk	Investigators were unaware of the allocation
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Double‐blind trial but no mention is made of the use of placebo equivalents for rifaximin and lactulose
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Double‐blind trial but no mention is made of the use of placebo equivalents for rifaximin and lactulose
Incomplete outcome data (attrition bias) All outcomes	Low risk	All participants were accounted for
Selective reporting (reporting bias)	Low risk	All outcomes were reported
Other bias	Low risk	No other bias identified
Overall bias assessment (mortality)	Low risk	No participants lost to follow‐up, and low overall risk of bias
Overall bias assessment (non‐mortality outcomes)	Low risk	Low overall risk of bias