Phenobarbital as an Adjuvant to benzodiazepines when compared to Single-agent benzodiazepine Treatment (usual care) for Alcohol withdrawal syndrome in the intensive care unit (PASTA): a study protocol

Background Abrupt cessation of alcohol consumption following hospital admission can induce alcohol withdrawal syndrome. This syndrome is challenging to manage and is associated with considerable morbidity and mortality. Current management of alcohol withdrawal syndrome in Australia is generally titrated benzodiazepine administration. In some regions, phenobarbital is preferred but evidence to support its superiority is weak. Methods We will conduct a single-center, three-arm, open-label, parallel-group, randomized clinical trial. Our primary objective is to determine the feasibility of embedding a randomized clinical trial within an electronic medical record to compare phenobarbital to single-agent benzodiazepine for patients with alcohol withdrawal. We will screen and randomize 45 patients using the Epic electronic medical record system. Patients will receive either low- or standard-dose intravenous phenobarbital (4 or 8 mg per kilogram), or usual care (benzodiazepine regimen). The primary outcomes to assess feasibility are usability, screening rates, enrollment rates, and compliance. Secondary outcomes are exploratory and include alcohol withdrawal scale scores, dose of benzodiazepine administered, health utilization, adjuvant drug treatments, and patient outcomes. Discussion There are limited high quality data evaluating the use of phenobarbital administration for alcohol withdrawal syndrome. Additionally, there is limited data evaluating the embedding of screening, randomization, and administration of a sedative drug within the electronic medical record. Our feasibility trial will establish whether this is possible within our health care system. In this protocol paper we detail how we will embed this trial within the electronic medical record Epic. Trial registration The study (RMH2024.320 v2 06/01/2025) is registered with Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12625000320459 . Registered on 17 April 2025. Trial Sponsor: The Royal Melbourne Hospital.