Amodio 1997.
Methods | Double‐blind, single‐centre, placebo‐controlled RCT. Cross‐over design: all participants underwent both intervention periods (received flumazenil and placebo). |
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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 6): 0%. |
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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. |
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Outcomes | Outcomes included in meta‐analyses: none. | |
Neuropsychiatric assessment |
Baseline and post infusion:
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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. |