Ketamine vs. Placebo as Adjunctive Therapies for Severe Alcohol Withdrawal

NCT ID: NCT02823977

Last Updated: 2018-01-19

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE4
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-02-28
• Study Completion Date: 2018-12-31

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.

Conditions

Alcohol Withdrawal

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Ketamine / Dexmedetomidine

Ketamine 0.25 mg/kg bolus followed by 0.5 mg/kg per hour AND Dexmedetomidine by continuous infusion at a fixed rate of 0.6 µg/kg per hour, both administered for up to 72 hours

Group Type: EXPERIMENTAL

Ketamine

Intervention Type: DRUG

Blinded study drug administered to experimental arm

Dexmedetomidine

Intervention Type: DRUG

Open-label study drug administered to both arms

Placebo / Dexmedetomidine

Normal saline, as a 500 mL infusion bag, to represent placebo AND Dexmedetomidine by continuous infusion at a fixed rate of 0.6 µg/kg per hour, both administered for up to 72 hours

Group Type: PLACEBO_COMPARATOR

Dexmedetomidine

Intervention Type: DRUG

Open-label study drug administered to both arms

Normal saline

Intervention Type: DRUG

Blinded comparator administered to control arm

Interventions

Ketamine

Blinded study drug administered to experimental arm

Intervention Type: DRUG

Dexmedetomidine

Open-label study drug administered to both arms

Intervention Type: DRUG

Normal saline

Blinded comparator administered to control arm

Intervention Type: DRUG

Other Intervention Names

Ketalar; Precedex; 0.9% NaCl in water

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Colorado, Denver

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Robert MacLaren, PharmD, MPH

Role: PRINCIPAL_INVESTIGATOR

University of Colorado, Denver

Locations

University of Colorado Hospital

Aurora, Colorado, United States

Countries

United States

Other Identifiers

16-1303

Identifier Type: -

Identifier Source: org_study_id