Dexmedetomidine as Adjunctive Therapy for Alcohol Withdrawal

NCT ID: NCT00936377

Last Updated: 2016-05-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-09-30
• Study Completion Date: 2012-10-31

Brief Summary

This study is designed to evaluate dexmedetomidine as adjunctive therapy of severe alcohol withdrawal of medical ICU patients. Specifically, this study will assess whether adjunctive dexmedetomidine reduces the doses of conventional agents used for alcohol withdrawal while maintaining patient comfort and safety and will explore if dexmedetomidine exhibits a dose-dependent profile of action when it is used for this indication. In addition, this study will assess the relationships between alcohol withdrawal, therapy with dexmedetomidine, and potential serum biomarkers of alcohol withdrawal.

Detailed Description

The objectives of this randomized, double-blind, placebo controlled, dose escalation study are a) to determine if adding dexmedetomidine to symptom-triggered, standard therapy of severe alcohol withdrawal reduces the dose requirements of conventional sedatives, analgesics, and neuroleptics; maintains patient comfort and safety; and prevents and shortens tracheal intubation; b) to explore whether dexmedetomidine acts in a dose-dependent manner to reduce the dose requirements of conventional sedatives, analgesics, and neuroleptics while maintaining patient comfort; and c) determine the association between alcohol withdrawal and potential serum biomarkers of alcohol withdrawal and assess whether these are expressed differently when dexmedetomidine is used as adjunctive therapy. Dexmedetomidine will be added to existing sedative therapies in an effort to decrease the use of these agents while maintaining patient comfort. The study will randomize twenty-four patients in a double-blind manner to receive placebo or dexmedetomidine at doses of 0.4 or 1.2 µg/kg per hour for a maximum duration of five days. All patients will be managed using an existing institution-specific, symptom-triggered alcohol withdrawal protocol.

Conditions

Acute Alcohol Withdrawal

Study Design

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

Study Groups

Dexmedetomidine, low dose

Dexmedetomidine 0.4 µg/kg per hour administered for a maximum duration of five days

Group Type: EXPERIMENTAL

Dexmedetomidine

Intervention Type: DRUG

Dexmedetomidine at 0.4 or 1.2 µg/kg per hour is administered for a maximum duration of five days

Dexmedetomidine, high dose

Dexmedetomidine 1.2 µg/kg per hour administered for a maximum duration of five days

Group Type: EXPERIMENTAL

Dexmedetomidine

Intervention Type: DRUG

Dexmedetomidine at 0.4 or 1.2 µg/kg per hour is administered for a maximum duration of five days

Placebo

Normal saline

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Normal saline for five days.

Interventions

Dexmedetomidine

Dexmedetomidine at 0.4 or 1.2 µg/kg per hour is administered for a maximum duration of five days

Intervention Type: DRUG

Placebo

Normal saline for five days.

Intervention Type: OTHER

Other Intervention Names

Precedex

Eligibility Criteria

Inclusion Criteria

1. Severe alcohol withdrawal defined by a CIWA score ≥ 15 and the need for at least 16 mg of lorazepam over a four-hour period. All lorazepam doses, whether oral or intravenous, will contribute to the cumulative amount.

2. Patients receiving standard therapy for severe alcohol withdrawal according to a symptom-triggered alcohol withdrawal protocol. 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).

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. Moribund state with planned withdrawal of life support.

8. Patients with known or suspected severe adverse reactions to dexmedetomidine (or clonidine).

9. Pregnant females or females suspected of being pregnant

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

Sponsors

Hospira, now a wholly owned subsidiary of Pfizer

INDUSTRY

Sponsor Role: collaborator

University of Colorado, Denver

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Robert MacLaren, PharmD

Role: PRINCIPAL_INVESTIGATOR

University of Colorado School of Pharmacy

Locations

University of Colorado Hospital

Aurora, Colorado, United States

Countries

United States

References

Reynolds PM, Mueller SW, MacLaren R. A comparison of dexmedetomidine and placebo on the plasma concentrations of NGF, BDNF, GDNF, and epinephrine during severe alcohol withdrawal. Alcohol. 2015 Feb;49(1):15-9. doi: 10.1016/j.alcohol.2014.11.006. Epub 2015 Jan 22.

Reference Type: DERIVED

PMID: 25638740 (View on PubMed)

Mueller SW, Preslaski CR, Kiser TH, Fish DN, Lavelle JC, Malkoski SP, MacLaren R. A randomized, double-blind, placebo-controlled dose range study of dexmedetomidine as adjunctive therapy for alcohol withdrawal. Crit Care Med. 2014 May;42(5):1131-9. doi: 10.1097/CCM.0000000000000141.

Reference Type: DERIVED

PMID: 24351375 (View on PubMed)

Other Identifiers

09-0406

Identifier Type: -

Identifier Source: org_study_id