Alcohol Withdrawal Syndrome Treated With Adjunctive Phenobarbital or Ketamine

Ketamine

Brief Summary

The goal of this study will aim to determine if adding phenobarbital or ketamine to a symptom-triggered benzodiazepine regimen decreases the rate of intensive care unit admissions during the treatment of alcohol withdrawal syndrome when compared to symptom-triggered benzodiazepine therapy alone.

Intervention / Treatment

prospective, randomized control trial
  • Ketamine (DRUG)
    Ketamine infusion
  • Phenobarbital (DRUG)
    Phenobarbital intravenous injection
  • Lorazepam (DRUG)
    Standard of Care
  • Placebo A (DRUG)
    Placebo injection
  • Placebo B (DRUG)
    Placebo infusion

Condition or Disease

  • Alcohol Withdrawal Syndrome

Phase

  • Phase 4

    • Study Design

    Study type: INTERVENTIONAL
    Status: Withdrawn
    Study results: No Results Available
    Age: 18 Years and older   (Adult, Older Adult)
    Enrollment: 0 (ACTUAL)
    Funded by: Other
    Allocation: Randomized
    Primary Purpose: Treatment

    Masking

    Each participant will be randomized according to a web-based randomization program employed by a research pharmacist once the Emergency Department provider deems the patient appropriate for inpatient treatment of alcohol withdrawal syndrome. Each medication will be packaged by Santa Barbara Cottage Hospital pharmacy. In order to blind both the clinicians and the participants, the pharmacy will provide medication bags that are identical. Therefore, Emergency Department nursing staff and physicians will be unaware of which study drug is being provided to the patient. Normal saline will be used as a placebo to mimic study drugs (phenobarbital and ketamine). Pharmacy will remain unblinded and maintain records of which treatment assignment is prepared for each patient. Treatment will be provided for the duration of the patient's hospitalization; therefore, treatment compliance will be documented in the electronic health record using the medication bag identifier.

    TRIPLE:
    • Participant
    • Care Provider
    • Investigator

    Clinical Trial Dates

    Start date: Apr 12, 2019 ESTIMATED
    Primary Completion: Apr 12, 2019 ACTUAL
    Completion Date: Apr 12, 2019 ACTUAL
    Study First Posted: Dec 28, 2018 ACTUAL
    Results First Posted: Aug 31, 2020
    Last Updated: Sep 17, 2019

    Sponsors / Collaborators

    Lead Sponsor: Santa Barbara Cottage Hospital
    Lead sponsor is responsible party
    Responsible Party: N/A

    The primary objective of this study is to compare phenobarbital and ketamine adjunctive therapies to lorazepam-based therapy in the treatment of acute alcohol withdrawal syndrome.

    It is hypothesized that the use of an alternative agent, either phenobarbital or ketamine, when used as an adjunct to symptom-triggered lorazepam therapy will significantly reduce the rate of intensive care unit admissions and thereby reduce the total cost associated with hospital admission for treatment of alcohol withdrawal syndrome.

    Enrolled patients will be admitted to Santa Barbara Cottage Hospital where they will be monitored with continuous pulse oximetry and cardiac telemetry. They will remain hospitalized while undergoing study-guided therapy in addition to supportive care for acute alcohol withdrawal syndrome. Patients will undergo standard of care therapy with lorazepam symptom-triggered therapy regardless of study participation.

    Participant Groups

    • Ketamine - infusion (0.15 - 0.4 mg/kg/hr) and placebo injections titrated by increases of 0.075 mg/kg/hr every 30 minutes for Clinical Institute Withdrawal Assessment for Alcohol (revised version) (CIWA-Ar) greater than or equal to 10 in addition to lorazepam symptom-triggered therapy Ketamine dosing will be based on ideal body weight Ketamine infusion will be discontinued once CIWA-Ar less than 10 for 4 hours

    • Phenobarbital - IV push (260 mg loading followed by 130 mg q1 hour) with placebo infusion until CIWA-Ar less than 10 with a maximum daily dose of 10mg/kg in addition to lorazepam symptom-triggered dosing for recurrent symptoms (Gold 2007) Maximum daily dose will be used in order to prevent over sedation as well as provide adequate storage in pharmacy monitored refrigerators for study drugs

    • Lorazepam will be administered every 30 minutes as indicated based on CIWA-Ar protocol for Cottage Health in addition to placebo injections and placebo infusion

    Eligibility Criteria

    Sex: All
    Minimum Age: 18
    Age Groups: Adult / Older Adult
    Healthy Volunteers: Yes

    Inclusion Criteria:

    * Primary admitting diagnosis of acute alcohol withdrawal syndrome based on International Statistical Classification of Diseases and Related Health Problems 10th Revision (ICD-10), code F10.3, F10.4.

    Exclusion Criteria:

    * Significant comorbid medical illness requiring Intensive Care Unit admission;
    * Pregnancy;
    * Inability to obtain intravenous access;
    * Child Pugh Class C; and
    * Allergy to study medications (phenobarbital, ketamine, lorazepam).

    Primary Outcomes

    • Number of admissions to the intensive care unit

    Secondary Outcomes

    • Number of patients with documented seizures while treated for alcohol withdrawal syndrome

    • CIWA-Ar scores (initial, maximum, discharge); Total score is cumulative of subscale measures: Minimum score is 0 (no evidence of alcohol withdrawal), Maximum score is 67 (severe alcohol withdrawal) Subscale measures: A) Nausea and vomiting (score 0-7); B) Tremor (score 0-7); C) Paroxysmal sweats (score 0-7); D) Anxiety (score 0-7); E) Tactile disturbances (score 0-7); F) Auditory disturbances (score 0-7); G) Visual disturbances (score 0-7); H) Headache, fullness in head (score 0-7); I) Agitation (score 0-7); J) Orientation and clouding of sensorium (score 0-4)

    • Cumulative dose of Lorazepam, Ketamine, and Phenobarbital

    • Number of patients who require Dexmedetomidine, Propofol or Benzodiazepine continuous infusions and average dose while being treated for alcohol withdrawal syndrome

    • Rate of intubation

    • Number of patients with documented auditory or visual hallucinations

    More Details

    NCT Number: NCT03788889
    Acronym: PKAT
    Other IDs: 18-94
    Study URL: https://clinicaltrials.gov/study/NCT03788889
    Last updated: Sep 29, 2023