Phenobarbital vs Ativan for Alcohol Withdrawal in the Intensive Care Unit

Overview

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.

Full Title of Study: “Phenobarbital Versus Ativan for Refractory Alcohol Withdrawal Treatment in the Intensive Care Unit”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: December 1, 2021

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.

Interventions

  • Drug: Phenobarbital
    • Phenobarbital loading dose followed by a taper will be given to control acute alcohol withdrawal syndrome
  • Drug: Lorazepam
    • Ativan will be given according to our institutional alcohol withdrawal protocol to control acute alcohol withdrawal syndrome

Arms, Groups and Cohorts

  • 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.
  • 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.

Clinical Trial Outcome Measures

Primary Measures

  • ICU length of stay
    • Time Frame: study completion, up to 18 months
    • number of days in the intensive care unit

Secondary Measures

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

Participating in This Clinical Trial

Inclusion Criteria

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

1. has required more than 10 mg of lorazepam within a one hour time period,

2. has required more than 30 mg of lorazepam within a four hour time period, or

3. 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:

1. has a traumatic brain injury or other neurological condition requiring frequent neurological assessment (stroke, intracranial hemorrhage, active seizures on admission)

2. has severe hypotension requiring vasopressor support

3. is less than 18 years of age

4. is actively pregnant

5. has an allergy to either of the drugs being studied (phenobarbital or lorazepam)

6. is already intubated at the time of randomization

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • OSF Healthcare System
  • Provider of Information About this Clinical Study
    • Principal Investigator: Bhagat Aulakh, Principal Investigator – OSF Healthcare System
  • Overall Official(s)
    • Bhagat Aulakh, MD, Principal Investigator, OSF St. Francis Medical Center
  • Overall Contact(s)
    • Rachael M Davis, MD, 309-655-7257, rachael.m.davis@osfhealthcare.org

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