PARTI: Phenobarbital vs Ativan for Alcohol Withdrawal in the Intensive Care Unit

Sponsor

OSF Healthcare System (Other)

Overall Status

Recruiting

CT.gov ID

NCT04156464

Collaborator

(none)

142

Enrollment

Location

Arms

19.8

Anticipated Duration (Months)

7.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Our aim is to compare outcomes of patients with benzodiazepine-refractory alcohol withdrawal syndrome who are treated with either a phenobarbital-based or a lorazepam based protocol.

Condition or Disease	Intervention/Treatment	Phase
Alcohol Withdrawal Alcohol Withdrawal Delirium	Drug: Phenobarbital Drug: Lorazepam	Phase 4

Detailed Description

This study is a prospective, open-label, randomized, controlled trial.
The electronic medical record will be used to identify patients who have a diagnosis of alcohol withdrawal or are receiving alcohol withdrawal. Subjects who are anticipated to meet inclusion criteria will be pre-consented for the study using an informed consent process. see informed consent form.
Subjects will not be enrolled and randomized until they have met inclusion criteria.
If a patient meets criteria, but is deemed non-decisional or unable to give consent, the patient's medical decision maker will undergo the informed consent process.
After enrollment, participants will be randomized to either the control group (lorazepam-based therapy) or the study group (phenobarbital-based therapy)
Personnel unassociated with patient screening, enrollment, or follow up will create the allocation sequence and will use a random, computerized number generator. The allocation sequence will then be transferred to sequentially numbered, opaque envelopes for purposes of allocation concealment. These sequentially numbered envelopes, which are blinded to clinical trial coordinators/physicians, will be handed out in order as patients are enrolled. Clinical trial coordinators/physicians will verify treatment eligibility and informed consent before opening the envelope to obtain the treatment assignment.
The study group will be placed on the phenobarbital-based protocol as described below in procedures. The control group will be placed on the lorazepam-based protocol, also listed below in procedures.
All medications in the study are FDA approved. No investigational medicines will be used.
Data will be collected on each participant as noted below in measurements.
The data will be analyzed and published as noted above in the statistical analysis plan and data use and management section.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

142 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

2 arms2 arms

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Phenobarbital Versus Ativan for Refractory Alcohol Withdrawal Treatment in the Intensive Care Unit

Actual Study Start Date :

Jul 6, 2020

Anticipated Primary Completion Date :

Dec 1, 2021

Anticipated Study Completion Date :

Mar 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Phenobarbital based treatment The phenobarbital group will undergo management with a phenobarbital based treatment protocol with additional symptom triggered therapies. On day 1, the phenobarbital group receive a loading dose of phenobarbital intravenous 10mg/kg (actual body weight) with a maximum dose of 1 g/100 mL On day 2 of study protocol, and no sooner than 12 hours after loading dose, phenobarbital 64.8 mg is administered every 12 hours for two doses. On day 3 of study protocol, patients will receive phenobarbital 32.4 mg every 12 hours for two doses. On day 4 of study protocol, patients will receive phenobarbital 32.4 mg once, to be given 24 hours after last scheduled dose. Throughout the 4 day protocol, the patient will have phenobarbital 65 mg every 6 hours as needed available either IM or IV, starting no sooner than 30 minutes after the loading dose.	Drug: Phenobarbital Phenobarbital loading dose followed by a taper will be given to control acute alcohol withdrawal syndrome Other Names: solfoton luminal
Active Comparator: Lorazepam based treatment The lorazepam group will undergo management with a lorazepam based treatment protocol with additional symptom triggered therapies. On Day 1, the lorazepam group will be started on scheduled lorazepam 4 mg every 6 hours After day 1, the scheduled lorazepam dose will be modified based on the total lorazepam requirements from the previous day and divided into 4-6 doses. A lorazepam infusion, at physician discretion, will be available at any point if the dose of scheduled and PRN lorazepam being given is too high or frequent to effectively be administered. Once symptoms are well controlled on lorazepam based therapy, the total dose given over the past 24 hours will be calculated and weaned by approximately 10-20% per day when clinically appropriate. Throughout the entire protocol, 2-4 mg lorazepam IV q 30 minutes PRN will be available for a goal CIWA <6 or RASS -1 to 0.	Drug: Lorazepam Ativan will be given according to our institutional alcohol withdrawal protocol to control acute alcohol withdrawal syndrome Other Names: ativan

Arm

Intervention/Treatment

Active Comparator: Phenobarbital based treatment

The phenobarbital group will undergo management with a phenobarbital based treatment protocol with additional symptom triggered therapies. On day 1, the phenobarbital group receive a loading dose of phenobarbital intravenous 10mg/kg (actual body weight) with a maximum dose of 1 g/100 mL On day 2 of study protocol, and no sooner than 12 hours after loading dose, phenobarbital 64.8 mg is administered every 12 hours for two doses. On day 3 of study protocol, patients will receive phenobarbital 32.4 mg every 12 hours for two doses. On day 4 of study protocol, patients will receive phenobarbital 32.4 mg once, to be given 24 hours after last scheduled dose. Throughout the 4 day protocol, the patient will have phenobarbital 65 mg every 6 hours as needed available either IM or IV, starting no sooner than 30 minutes after the loading dose.

Drug: Phenobarbital

Phenobarbital loading dose followed by a taper will be given to control acute alcohol withdrawal syndrome

Other Names:

solfoton

luminal

Active Comparator: Lorazepam based treatment

The lorazepam group will undergo management with a lorazepam based treatment protocol with additional symptom triggered therapies. On Day 1, the lorazepam group will be started on scheduled lorazepam 4 mg every 6 hours After day 1, the scheduled lorazepam dose will be modified based on the total lorazepam requirements from the previous day and divided into 4-6 doses. A lorazepam infusion, at physician discretion, will be available at any point if the dose of scheduled and PRN lorazepam being given is too high or frequent to effectively be administered. Once symptoms are well controlled on lorazepam based therapy, the total dose given over the past 24 hours will be calculated and weaned by approximately 10-20% per day when clinically appropriate. Throughout the entire protocol, 2-4 mg lorazepam IV q 30 minutes PRN will be available for a goal CIWA <6 or RASS -1 to 0.

Drug: Lorazepam

Ativan will be given according to our institutional alcohol withdrawal protocol to control acute alcohol withdrawal syndrome

Other Names:

ativan

Outcome Measures

Primary Outcome Measures

ICU length of stay [study completion, up to 18 months]
number of days in the intensive care unit

Secondary Outcome Measures

Hospital length of stay [Study completion, up to 18 months]
number of days in the hospital
30-day readmission [study complettion, up to 18 months]
rate of readmission of patients within 30 days for any cause
mortality [Study completion, up to 18 months]
number of deaths
Intubation [study completion, up to 18 months]
rate of endotracheal intubation
Hospitalization cost [Study completion, up to 18 months]
Cost of index hospital stay
Lorazepam use [Study completion, up to 18 months]
total lorazepam use in mg during the entire hospital stay
dexmedetomidine use [Study completion, up to 18 months]
total dexmedetomidine used in mcg during the entire hospital stay
propofol use [Study completion, up to 18 months]
total propofol used in mg during the entire hospital stay

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients will be eligible for randomization if he/she has met one of the following three conditions:

has required more than 10 mg of lorazepam within a one hour time period,
has required more than 30 mg of lorazepam within a four hour time period, or
requires admission/transfer to the intensive care unit for primarily uncontrolled alcohol withdrawal symptoms

Exclusion Criteria:

Patients will be excluded from the study if he/she:

has a traumatic brain injury or other neurological condition requiring frequent neurological assessment (stroke, intracranial hemorrhage, active seizures on admission)
has severe hypotension requiring vasopressor support
is less than 18 years of age
is actively pregnant
has an allergy to either of the drugs being studied (phenobarbital or lorazepam)
is already intubated at the time of randomization