Amodio 1997

Methods	Double‐blind, single‐centre, placebo‐controlled RCT. Cross‐over design: all participants underwent both intervention periods (received flumazenil and placebo).
Participants	13 participants with cirrhosis with no evidence of overt hepatic encephalopathy but with abnormal brainstem evoked potentials (5 participants) or prolonged Number Connection Test times (6 participants), or both at baseline corresponding to a diagnosis of minimal hepatic encephalopathy. Mean ± SD age: flumazenil/placebo: 54 ± 7 years. Proportion of men: 77%. Aetiology of cirrhosis: alcohol 77%; hepatitis B/C 15%. Proportion testing positive for benzodiazepines at baseline (Table 7): 0%.
Interventions	Intervention comparison: intravenous bolus flumazenil 1 mg followed by 4 boluses of 0.5 mg every 30 minutes versus placebo (saline). Total dose of flumazenil: 3 mg. Washout period: 72 hours before cross‐over to the alternative arm. Cointerventions: none described.
Outcomes	Outcomes included in meta‐analyses: none.
Neuropsychiatric assessment	Baseline and post infusion: Brainstem auditory evoked potentials; Number Connection Test.
Inclusion period (date)	Not described.
Country	Italy.
Notes	Included data: RCT did not describe outcomes for first intervention period. Therefore, we were unable to include the trial in our meta‐analyses. The study report includes 2 tables containing data for the 5 participants with abnormal evoked potentials at baseline and the 6 participants with abnormal Number Connection Test times. There were no change in the group mean variables after flumazenil.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Not described.
Allocation concealment (selection bias)	Low risk	Concealed drug containers.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Blinding of participants and personnel.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Blinding of outcome assessment.
Incomplete outcome data (attrition bias) All outcomes	Low risk	No missing outcome data.
Selective reporting (reporting bias)	Low risk	Trial described clinically relevant outcomes. We had no access to information about outcomes described in the original protocol or information in trial registries.
For‐profit funding	Low risk	Funding from the Italian Liver Foundation.
Other bias	Low risk	No other biases.
Overall assessment	High risk	High risk of bias.