Gooday 1995.
Methods | Double‐blind, single‐centre, placebo‐controlled RCT. Cross‐over design: all participants were crossed over to alternative intervention. |
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Participants | 10 participants with cirrhosis and subclinical (corresponding to minimal) hepatic encephalopathy diagnosed based on a score on the Digit Symbol Substitution test of < 1 SD of the age‐matched normative mean. Mean age ± SD: 53.9 ± 7.4 years. Proportion of men: 80%. Aetiology of cirrhosis: alcohol 60%; hepatitis B/C 20%. Proportion testing positive for benzodiazepines at baseline (Table 6): apparently not performed, though not specifically stated. |
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Interventions |
Intervention comparison: intravenous infusion flumazenil 0.2 mg over an unspecified time versus placebo (saline). Total dose of flumazenil: 0.2 mg. Washout period: 1 week. Cointerventions: none described. |
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Outcomes | Outcomes included in meta‐analyses: mortality and serious adverse events (Table 7) assessed at end of the intervention. | |
Neuropsychiatric assessment |
At baseline:
At baseline and post infusion:
Duration of follow‐up and timing of tests not described. |
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Inclusion period (date) | Not described. | |
Country | UK. | |
Notes | Included data: we received additional (unpublished) information about the trial methods and number of participants allocated to flumazenil/placebo during the first allocation period via email in 2003 when conducting the previous version of this review. The trial did not evaluate the number of participants with an overall improvement in hepatic encephalopathy. Therefore, we were unable to include the trial in our analyses of this outcome measure. | |
Risk of bias | ||
Bias | Authors' judgement | Support for judgement |
Random sequence generation (selection bias) | Low risk | Random number table. |
Allocation concealment (selection bias) | Low risk | Serially numbered opaque sealed envelopes used in administration of 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 | Unclear risk | No information provided. |
Other bias | High risk | Primary investigators described a significant drug by order and group by drug by order interaction. |
Overall assessment | High risk | High risk of bias. |