Phenobarbital for the management of severe acute alcohol withdrawal (the PHENOMANAL trial): a pilot randomized controlled trial
Niall Filewod, Stephen Hwang, Christian J Turner, Leena Rizvi, Sara Gray, Michelle Klaiman, Danielle Buell, Johnathan Ailon, Alexander Caudarella, Galo F Ginocchio, Marlene Santos, Gyan Sandhu, Norman Dewhurst, Kelly Sequeira, Karen E A Burns, Niall Filewod, Stephen Hwang, Christian J Turner, Leena Rizvi, Sara Gray, Michelle Klaiman, Danielle Buell, Johnathan Ailon, Alexander Caudarella, Galo F Ginocchio, Marlene Santos, Gyan Sandhu, Norman Dewhurst, Kelly Sequeira, Karen E A Burns
Abstract
Background: Benzodiazepines are considered first-line treatment for patients experiencing severe acute alcohol withdrawal syndrome (sAAWS). Although several medications have been evaluated as potential adjuvant treatments for sAAWS, barbiturates show particular promise.
Objective: In the PHENOMANAL trial, we will assess the feasibility of conducting an allocation-concealed, quadruple-blinded, randomized controlled trial (RCT) comparing symptom-triggered benzodiazepine therapy with either a single dose of adjuvant intravenous (IV) phenobarbital (7.5 mg/kg of ideal body weight) or a single dose of matching IV placebo for patients with sAAWS.
Methods: We will recruit adult patients from the Emergency Department, Intensive Care Unit, or hospital wards with a Clinical Institute of Withdrawal - Adult revised (CIWA-Ar) score of 16 or more after receipt of at least 60 mg of diazepam or equivalent within 16 h of diagnosis of sAAWS, and an anticipated need for hospitalization. We will randomize participants (n=39) in a 2:1 manner to treatment and placebo groups, respectively. The primary objective of the PHENOMANAL pilot trial will be to demonstrate our ability to recruit the desired population over the trial period. As secondary objectives, we will evaluate clinician compliance with the treatment protocols, assess crossover rates from the placebo arm to the treatment arm, and obtain preliminary estimates of treatment effect. All trial participants will be followed for 7 days or until hospital discharge.
Relevance: The PHENOMANAL trial is novel in investigating a new treatment for a common and understudied condition, repurposing an existing medication for a novel indication, and addressing an important evidence gap. Through conduct of the multidisciplinary pilot trial, we aim to advance methodology in acute care research through the use of a hybrid consent model and inform the design of a large-scale trial.
Trial registration: ClinicalTrials.gov Registration NCT03586089 ; first registered July 13, 2018.
Keywords: Delirium tremens; Phenobarbital; Alcohol withdrawal; Treatment.
Conflict of interest statement
None of the authors have financial or non-financial competing interests related to the topic of the trial to declare.
© 2022. The Author(s).
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Source: PubMed