Alcohol Withdrawal Syndrome Treated With Adjunctive Phenobarbital or Ketamine

NCT03788889 | Withdrawn Phase 4 FDA Drug

• 1 other identifier: 18-94
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Alcohol Withdrawal Syndrome

Keywords

Lorazepam; Ketamine; Phenobarbital

Outcome Measures

Primary Outcomes (1)

• Intensive Care Unit admission rate

  Number of admissions to the intensive care unit

  Presentation to Emergency Department through hospital stay, data will be utilized through study completion, anticipated 2 years

Secondary Outcomes (6)

• Incidence of withdrawal seizures

  Presentation to Emergency Department through hospital stay, data will be utilized through study completion, anticipated 2 years

• Clinical Institute Withdrawal Assessment of Alcohol Scale, Revised (CIWA-Ar) scores

  Presentation to Emergency Department through hospital stay, data will be utilized through study completion, anticipated 2 years

• Cumulative dose of medication/s administered

  Presentation to Emergency Department through hospital stay, data will be utilized through study completion, anticipated 2 years

• Incidence of refractory alcohol withdrawal requiring alternative sedation with dexmedetomidine, propofol or midazolam infusions

  Presentation to Emergency Department through hospital stay, data will be utilized through study completion, anticipated 2 years

• Rate of mechanical ventilation

  Presentation to Emergency Department through hospital stay, data will be utilized through study completion, anticipated 2 years

Study Arms (3)

Lorazepam + Ketamine + Placebo A

ACTIVE COMPARATOR

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; Drug: Lorazepam; Drug: Placebo A

Lorazepam + Phenobarbital + Placebo B

ACTIVE COMPARATOR

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; Drug: Lorazepam; Drug: Placebo B

Lorazepam + Placebo A + Placebo B

PLACEBO COMPARATOR

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; Drug: Placebo A; Drug: Placebo B

Interventions

Ketamine DRUG

Ketamine infusion

Also known as: Ketalar

Lorazepam + Ketamine + Placebo A

Phenobarbital DRUG

Phenobarbital intravenous injection

Also known as: Solfoton, Luminal

Lorazepam + Phenobarbital + Placebo B

Lorazepam DRUG

Standard of Care

Also known as: Ativan

Lorazepam + Ketamine + Placebo A; Lorazepam + Phenobarbital + Placebo B; Lorazepam + Placebo A + Placebo B

Placebo A DRUG

Placebo injection

Also known as: Normal saline

Lorazepam + Ketamine + Placebo A; Lorazepam + Placebo A + Placebo B

Placebo B DRUG

Placebo infusion

Also known as: Normal saline

Lorazepam + Phenobarbital + Placebo B; Lorazepam + Placebo A + Placebo B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Santa Barbara Cottage Hospital: lead

MeSH Terms

Interventions

Ketamine; Phenobarbital; Lorazepam; Saline Solution

Intervention Hierarchy (Ancestors)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Barbiturates; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzodiazepinones; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Noah Stites-Hallet, MD

  Santa Barbara Cottage Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: prospective, randomized control trial

Study Record Dates

• First Submitted: December 22, 2018
• First Posted: December 28, 2018
• Study Start: April 12, 2019
• Primary Completion: April 12, 2019
• Study Completion: April 12, 2019
• Last Updated: September 19, 2019

Record last verified: 2019-09

Data Sharing

• IPD Sharing: Will not share