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Alcohol Withdrawal Syndrome Treated With Adjunctive Phenobarbital or Ketamine (PKAT)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03788889
Recruitment Status : Withdrawn (internal practice and policy limitations including time commitment / workflow issues)
First Posted : December 28, 2018
Last Update Posted : September 19, 2019
Sponsor:
Information provided by (Responsible Party):
Santa Barbara Cottage Hospital

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.

Condition or disease Intervention/treatment Phase
Alcohol Withdrawal Syndrome Drug: Ketamine Drug: Phenobarbital Drug: Lorazepam Drug: Placebo A Drug: Placebo B Phase 4

Detailed Description:

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: prospective, randomized control trial
Masking: Triple (Participant, Care Provider, Investigator)
Masking Description:

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.

Primary Purpose: Treatment
Official Title: A Randomized, Double-Blinded, Placebo-Controlled Study Evaluating Phenobarbital and Ketamine Adjunctive Therapies in the Treatment of Alcohol Withdrawal Syndrome
Estimated Study Start Date : April 12, 2019
Actual Primary Completion Date : April 12, 2019
Actual Study Completion Date : April 12, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Lorazepam + Ketamine + Placebo A

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

Drug: Ketamine
Ketamine infusion
Other Name: Ketalar

Drug: Lorazepam
Standard of Care
Other Name: Ativan

Drug: Placebo A
Placebo injection
Other Name: Normal saline

Active Comparator: Lorazepam + Phenobarbital + Placebo B

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

Drug: Phenobarbital
Phenobarbital intravenous injection
Other Name: Solfoton, Luminal

Drug: Lorazepam
Standard of Care
Other Name: Ativan

Drug: Placebo B
Placebo infusion
Other Name: Normal saline

Placebo Comparator: Lorazepam + Placebo A + Placebo B
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
Drug: Lorazepam
Standard of Care
Other Name: Ativan

Drug: Placebo A
Placebo injection
Other Name: Normal saline

Drug: Placebo B
Placebo infusion
Other Name: Normal saline




Primary Outcome Measures :
  1. Intensive Care Unit admission rate [ Time Frame: Presentation to Emergency Department through hospital stay, data will be utilized through study completion, anticipated 2 years ]
    Number of admissions to the intensive care unit


Secondary Outcome Measures :
  1. Incidence of withdrawal seizures [ Time Frame: Presentation to Emergency Department through hospital stay, data will be utilized through study completion, anticipated 2 years ]
    Number of patients with documented seizures while treated for alcohol withdrawal syndrome

  2. Clinical Institute Withdrawal Assessment of Alcohol Scale, Revised (CIWA-Ar) scores [ Time Frame: Presentation to Emergency Department through hospital stay, data will be utilized through study completion, anticipated 2 years ]

    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)


  3. Cumulative dose of medication/s administered [ Time Frame: Presentation to Emergency Department through hospital stay, data will be utilized through study completion, anticipated 2 years ]
    Cumulative dose of Lorazepam, Ketamine, and Phenobarbital

  4. Incidence of refractory alcohol withdrawal requiring alternative sedation with dexmedetomidine, propofol or midazolam infusions [ Time Frame: Presentation to Emergency Department through hospital stay, data will be utilized through study completion, anticipated 2 years ]
    Number of patients who require Dexmedetomidine, Propofol or Benzodiazepine continuous infusions and average dose while being treated for alcohol withdrawal syndrome

  5. Rate of mechanical ventilation [ Time Frame: Presentation to Emergency Department through hospital stay, data will be utilized through study completion, anticipated 2 years ]
    Rate of intubation

  6. Incidence of alcohol withdrawal hallucinations [ Time Frame: Presentation to Emergency Department through hospital stay, data will be utilized through study completion, anticipated 2 years ]
    Number of patients with documented auditory or visual hallucinations



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03788889


Sponsors and Collaborators
Santa Barbara Cottage Hospital
Investigators
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Principal Investigator: Noah Stites-Hallet, MD Santa Barbara Cottage Hospital

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Responsible Party: Santa Barbara Cottage Hospital
ClinicalTrials.gov Identifier: NCT03788889    
Other Study ID Numbers: 18-94
First Posted: December 28, 2018    Key Record Dates
Last Update Posted: September 19, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Keywords provided by Santa Barbara Cottage Hospital:
Lorazepam
Ketamine
Phenobarbital
Additional relevant MeSH terms:
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Syndrome
Substance Withdrawal Syndrome
Disease
Pathologic Processes
Substance-Related Disorders
Chemically-Induced Disorders
Mental Disorders
Ketamine
Lorazepam
Phenobarbital
Central Nervous System Depressants
Physiological Effects of Drugs
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Anesthetics, Dissociative
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Anticonvulsants
Antiemetics
Autonomic Agents
Gastrointestinal Agents
Hypnotics and Sedatives
Anti-Anxiety Agents
Tranquilizing Agents