Vyas 2017.

Study characteristics
Methods	Randomised, open‐label clinical trial
Participants	The trial assessed the effects of lactulose plus rifaximin or lactulose alone in participants with cirrhosis and acute‐on‐chronic liver failure who were admitted to hospital with grade III/IV hepatic encephalopathy. There were 38 participants in the rifaximin plus lactulose group and 35 in the lactulose alone group. Age Not reported Proportion of men Not reported Aetiology of cirrhosis Not reported
Interventions	86 participants initially received lactulose 100 ml followed by 30 ml hourly for 24 hours to ensure passage of 4 to 6 bowel movements. The 73 participants in whom blood ammonia concentration were still > 70 ug/dl following purgation were then randomised as follows. Intervention: rifaximin 400 mg every 8 hours plus enteral lactulose 30 ml every 6 hours Control group: lactulose 30 ml every 6 hours Co‐interventions: none Duration of treatment: 72 hours Follow‐up duration: 30 days
Outcomes	Neuropsychiatric assessment Mental status (most likely West Haven criteria); blood ammonia
Inclusion period	November 2014 to December 2015
Outcomes included in meta‐analyses	Mortality, hepatic encephalopathy, blood ammonia (primary end point attainment of a blood ammonia of 70 mg/dl; this was achieved in 21.1% of participants on lactulose and 22.9% on rifaximin plus lactulose, but data were not extractable for our meta‐analysis).
Country of origin	Single centre in India
Notes	Publication status: abstract only Vested interests bias: none Additional information: authors contacted on 11 April 2021 for further information on participant and study characteristics, randomisation methods and concealment of allocation, handling of incomplete outcome data, clarification of data extracted regarding hepatic encephalopathy outcomes, and data on our secondary outcomes. We also requested access to their blood ammonia data by treatment groups rather than as a 'primary end point'; still awaiting response.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Active arm was randomised but no details provided.
Allocation concealment (selection bias)	High risk	Participants had already been treated with lactulose, so unclear if the allocation to additional treatment was concealed.
Blinding of participants and personnel (performance bias) All outcomes	High risk	This was an open‐label study.
Blinding of outcome assessment (detection bias) All outcomes	High risk	This was an open‐label study.
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Outcome data presented as percentages not as actual numbers.
Selective reporting (reporting bias)	High risk	Compared to the trial registry, outcomes of duration of hepatic encephalopathy post‐inclusion, and duration of intensive care unit stay, were not reported by the authors.
Other bias	Low risk	No other biases identified.
Overall bias assessment (mortality)	Unclear risk	Deaths reported for both arms and, within the total population, for those in whom blood ammonia did or did not improve, but as percentages rather than actual numbers.
Overall bias assessment (non‐mortality outcomes)	High risk	Selection, performance, detection bias selective reporting bias identified as high risk.