Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12625000320459
Ethics application status
Approved
Date submitted
4/04/2025
Date registered
17/04/2025
Date last updated
17/04/2025
Date data sharing statement initially provided
17/04/2025
Type of registration
Prospectively registered

Titles & IDs
Public title
Phenobarbital in combination benzodiazepine administration compared to benzodiazepine-only Treatment (usual care) for Alcohol Withdrawal Syndrome in the Intensive Care Unit
Scientific title
Phenobarbital as an Adjuvant to benzodiazepine administration when compared to Single-agent benzodiazepine Treatment (usual care) for Alcohol Withdrawal Syndrome in the Intensive Care Unit (PASTA): A single centre, three-arm, parallel group, electronic medical records embedded and randomised, feasibility trial
Secondary ID [1] 314139 0
None
Universal Trial Number (UTN)
Trial acronym
PASTA
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Alcohol Withdrawal Syndrome 336951 0
Delirium Tremens 336953 0
Alcohol Use Disorder 336952 0
Alcohol Abuse 336954 0
Condition category
Condition code
Mental Health 333423 333423 0 0
Addiction
Injuries and Accidents 333424 333424 0 0
Poisoning

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
ARM 1. Intravenous infusion Phenobarbital low-dose (4 mg/kg ideal body weight) over 30 minutes + usual care. Thirty minutes after the initial phenobarbital administration, up to two additional intravenous infusion of 2 mg/kg (ideal body weight) can be administered as required in a 48-hour period. Phenobarbital administration will be limited to a 48-hour period of administration.

ARM 2. Intravenous infusion Phenobarbital standard-dose (8 mg/kg ideal body weight) over 30 minutes + usual care. Thirty minutes after the initial phenobarbital administration, up to two additional intravenous infusion of 2 mg/kg (ideal body weight) can be administered as required in a 48-hour period. Phenobarbital administration will be limited to a 48-hour period of administration.

Adherence to the control will be monitored by confirmation of administration on the electronic medical records system (Epic EMR).
Intervention code [1] 330725 0
Treatment: Drugs
Comparator / control treatment
Control arm is usual care - which at The Royal Melbourne Hospital is diazepam 20mg orally (as oral tablet, OR crushed and administered via. nasogastric tube where necessary) every 2 hours as required per Alcohol Withdrawal Scale, with a recommended maximum 120mg in 24 hours.

Adherence to the control will be monitored by confirmation of administration on the electronic medical records system (Epic EMR).
Control group
Active

Outcomes
Primary outcome [1] 340993 0
Feasibility
Timepoint [1] 340993 0
Feasibility determinants will be assessed throughout the trial. Positive screen will be assessed monthly for the duration of the trail.
Primary outcome [2] 341077 0
Feasibility
Timepoint [2] 341077 0
70% of eligible patients being randomised, and trial completion being within 2.5 years will be assessed every 3 months for the duration of the trial.
Primary outcome [3] 341078 0
Feasibility
Timepoint [3] 341078 0
This outcome will be assessed every 3 month for the duration of the trial.
Secondary outcome [1] 445713 0
Delirium-Free Days
Timepoint [1] 445713 0
N.B. All ICU patients have a CAM-ICU/RASS score reported at least twice a day as a part of standard clinical care. This secondary outcome will be assessed every calendar day of participant enrolment until ICU discharge.
Secondary outcome [2] 446111 0
Feasibility (PRIMARY OUTCOME)
Timepoint [2] 446111 0
This outcome will be assessed every 6 months for the duration of the trial

Eligibility
Key inclusion criteria
• Equals or greater than 18 years old
• Admitted to the ICU and has Alcohol Withdrawal Syndrome requiring treatment; determined as having received greater than 20 mg of diazepam, or diazepam equivalents, within a 6-hour period or greater than 40 mg of diazepam within a 24-hour period.
Minimum age
18 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Greater than 75 years old
• Pregnant or breast feeding
• A cause other than alcohol withdrawal is thought to be more likely for delirium
• Admission with polypharmacy overdose and substantial co-ingestion of a CNS depressant drugs (opioids, benzodiazepines, quetiapine or gamma-hydroxy-butyrate) is documented.
• Taking phenobarbital prior to admission
• Known allergy or hypersensitivity syndrome to phenobarbital, primidone, or carbamazepine
• Allergy or rash with other antiepileptics
• On existing evidence is highly likely to discharge against medical advice or die in the next 24 hours
• Goals of care are B2 or less (i.e., not for tracheal intubation)
• Inability to obtain intravenous access
• Acute Kidney Injury Stage 3
• Phenobarbital contraindicated for patient due to local product information
o Current treatment with drug known to interact with phenobarbital, i.e., ticagrelor, prasugrel, warfarin, a direct oral anticoagulant, enteral/parenteral calcineurin inhibitor, or HIV-protease inhibitor.
o History of porphyria
o History of myasthenia gravis
o Decompensated liver cirrhosis or severe liver disease (determined by an INR greater than 5.0 due to underlying liver disease).

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
The screening of eligible patient will be automatically and silently perform by the electronic medical records (EMR) in real time. When a patient becomes eligible, the prescriber will be prompted by OPA alert to review study exclusion and randomize the patient. The randomization will occur once the prescriber clicks the “Randomize” button that will send a query to the randomization schedule. The prescriber will be informed of the participant allocation and will enter the allocated arm within the OPA alert. The study treatment is concealed from the prescriber during the randomization process
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Stratified randomization will be used, and the schedule will be provided by the statistician. The method of sequence generation employed in the study will be stratified randomisation using a randomisation table created by computer software. The only factor used for stratification in this study is sex (male/female).
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint/s
Efficacy
Statistical methods / analysis
Given the feasibility methodology, the statistical approach will predominately be descriptive. Any inferential statistical testing will be done using chi-squared test (or Fisher’s exact test) or unpaired Student’s T test (or Wilcoxon rank-sum test) for binary and continuous outcomes as appropriate.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
30/04/2025
Actual
Date of last participant enrolment
Anticipated
1/04/2027
Actual
Date of last data collection
Anticipated
30/04/2027
Actual
Sample size
Target
45
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment postcode(s) [1] 43889 0
3050 - Royal Melbourne Hospital

Funding & Sponsors
Funding source category [1] 318647 0
Self funded/Unfunded
Name [1] 318647 0
Genuinely unfunded
Country [1] 318647 0
Primary sponsor type
Hospital
Name
The Royal Melbourne Hospital
Address
Country
Australia
Secondary sponsor category [1] 321068 0
None
Name [1] 321068 0
Address [1] 321068 0
Country [1] 321068 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 317258 0
The Royal Melbourne Hospital Human Research Ethics Committee
Ethics committee address [1] 317258 0
Ethics committee country [1] 317258 0
Australia
Date submitted for ethics approval [1] 317258 0
25/11/2024
Approval date [1] 317258 0
19/02/2025
Ethics approval number [1] 317258 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 140490 0
Prof Adam Deane
Address 140490 0
The Royal Melbourne Hospital, 300 Grattan Street, Parkville, 3050, Melbourne, Victoria
Country 140490 0
Australia
Phone 140490 0
+61 03 9342 9253
Fax 140490 0
Email 140490 0
[email protected]
Contact person for public queries
Name 140491 0
Samuel Ricciardone
Address 140491 0
The Royal Melbourne Hospital, 300 Grattan Street, Parkville, 3050, Melbourne, Victoria
Country 140491 0
Australia
Phone 140491 0
+61 03 9342 9270
Fax 140491 0
Email 140491 0
[email protected]
Contact person for scientific queries
Name 140492 0
Adam Deane
Address 140492 0
The Royal Melbourne Hospital, 300 Grattan Street, Parkville, 3050, Melbourne, Victoria
Country 140492 0
Australia
Phone 140492 0
+61 03 9342 9253
Fax 140492 0
Email 140492 0
[email protected]

Data sharing statement
Will the study consider sharing individual participant data?
No


What supporting documents are/will be available?

No Supporting Document Provided


Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.