Clinical trial NCT02823977: Ketamine vs. Placebo as Adjunctive Therapies for Severe Alcohol Withdrawal
Official title: A Randomized, Double-blind Study of Ketamine / Dexmedetomidine vs. Placebo / Dexmedetomidine as Adjunctive Therapies for Severe Alcohol Withdrawal
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE4
Conditions: Alcohol Withdrawal
Keywords: ketamine
dexmedetomidine
alcohol
Lead sponsor: University of Colorado, Denver
Sponsor class: OTHER
First posted: 2016-07-06
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is designed to evaluate the addition of ketamine to dexmedetomidine as adjunctive therapies of severe alcohol withdrawal in medical ICU patients. Specifically, this study will assess whether the combination of ketamine and dexmedetomidine reduces the doses of conventional agents used for alcohol withdrawal while maintaining patient comfort and safety and will explore if the combination alters the expression of catecholamines in the serum over time.

Detailed description: The combination of ketamine and dexmedetomidine for alcohol withdrawal is pharmacologically rationale and may provide additive benzodiazepine-sparing effects. All subjects will receive benzodiazepine therapy as standard of care.

The objectives of this randomized, double-blind pilot study of 20 subjects with severe alcohol withdrawal are to a) determine if adding ketamine 0.5 mg/kg per hour to dexmedetomidine 0.6 µg/kg per hour (both agents administered for up to 72 hours) as adjunctive therapies to a symptom-triggered benzodiazepine protocol reduces the dose requirements of conventional sedatives while maintaining patient comfort and safety; and to b) explore whether epinephrine, a marker of autonomic activity, is expressed differently when ketamine is added to dexmedetomidine as adjunctive therapies.

Eligibility criteria: Inclusion Criteria:

1. Severe alcohol withdrawal defined by a CIWA score ≥ 15 and the need for at least 16 mg of lorazepam equivalents over a four-hour period. All benzodiazepine and barbiturate doses, whether oral or intravenous, will contribute to the cumulative amount using the following conversion: 1 mg lorazepam = 2 mg midazolam = 7.5 mg clorazepate = 15 mg phenobarbital.
2. Patients receiving standard therapy for severe alcohol withdrawal according to the UCH-specific, symptom-triggered alcohol withdrawal protocol in the ICU (or admission to the ICU is anticipated). Lorazepam is the preferred benzodiazepine agent for patients requiring ICU admission due to alcohol withdrawal.
3. Informed consent within 36 hours of qualifying for the study.

Exclusion Criteria:

1. Patients \< 18 years of age or \> 85 years of age.
2. Patients receiving benzodiazepine therapy for purposes other than alcohol withdrawal (e.g. sedation, seizure control other than alcohol withdrawal).
3. Patients with alcohol withdrawal not requiring ICU admission.
4. Patients receiving epidural administration of medication(s).
5. Comatose patients by metabolic or neurologic affectation.
6. Patients with active myocardial ischemia or second- or third-degree heart block.
7. Patients with Child-Pugh score of C.
8. Moribund state with planned withdrawal of life support.
9. Patient pending transfer to another facility.
10. Patients with known or suspected severe adverse reactions to dexmedetomidine (or clonidine) or ketamine.
11. Pregnant females or females suspected of being pregnant.
12. Prisoners or active parolees.
13. Previous study participation.
14. Patients already receiving ketamine for alcohol withdrawal. Patients receiving dexmedetomidine will be excluded if the infusion exceeds 1 µg/kg per hour for more than two hours or any rate for a cumulative duration of 12 hours.

Primary outcomes:
measure: Cumulative Lorazepam Dose Over the First 12 Hours of Alcohol Withdrawal
timeFrame: 12 hours
measure: Cumulative Lorazepam Dose Over the First 24 Hours of Alcohol Withdrawal
timeFrame: 24 hours
measure: Cumulative Lorazepam Dose Over the 72 Hours of Alcohol Withdrawal
timeFrame: 72 hours
Secondary outcomes:
measure: Change in 12-Hour Lorazepam Requirement Pre- and Post-Treatment
timeFrame: 12 hours before treatment, 12 hours after treatment on first day of starting study drug
measure: Change in 24-Hour Lorazepam Requirement Pre- and Post-Treatment
timeFrame: 24 hours before treatment, 24 hours after treatment on first day of starting study drug
measure: The Degree of Alcohol Withdrawal Assessed by Clinical Institute Withdrawal Assessment (CIWA) Scores
timeFrame: 72 hours
measure: The Occurrence of Adverse Events: hypotension, hypertension, bradycardia, tachycardia
timeFrame: 72 hours
measure: Plasma Epinephrine Concentrations Across Groups Over Time
timeFrame: 96 hours
Other outcomes:
Locations:
city: Aurora
country: United States
facility: University of Colorado Hospital
state: Colorado
Study officials:
affiliation: University of Colorado, Denver
name: Robert MacLaren, PharmD, MPH
role: PRINCIPAL_INVESTIGATOR
References: