Dexmedetomidine as Adjunctive Therapy for Alcohol Withdrawal (DATA)

A Randomized, Double-Blind, Placebo Controlled, Dose Escalation Study of Dexmedetomidine as Adjunctive Therapy for Alcohol Withdrawal

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.

Study Overview

• Status: Completed
• Conditions: Acute Alcohol Withdrawal
• Intervention / Treatment: Drug: Dexmedetomidine; Other: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Dexmedetomidine, low dose; Dexmedetomidine 0.4 µg/kg per hour administered for a maximum duration of five days	Drug: Dexmedetomidine; Dexmedetomidine at 0.4 or 1.2 µg/kg per hour is administered for a maximum duration of five days; Other Names: Precedex
EXPERIMENTAL: Dexmedetomidine, high dose; Dexmedetomidine 1.2 µg/kg per hour administered for a maximum duration of five days	Drug: Dexmedetomidine; Dexmedetomidine at 0.4 or 1.2 µg/kg per hour is administered for a maximum duration of five days; Other Names: Precedex
PLACEBO_COMPARATOR: Placebo; Normal saline	Other: Placebo; Normal saline for five days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Cumulative Lorazepam Dose Over the First Seven Days of Alcohol Withdrawal	Seven days
Change in 12-Hour Lorazepam Requirement Pre- and Post-Treatment	12 hours before treatment, 12 hours after treatment on first day of starting study drug
Change in 24-Hour Lorazepam Requirement Pre- and Post-Treatment	24 hours before treatment, 24 hours after treatment on first day of starting study drug

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Degree of Alcohol Withdrawal Assessed by Clinical Institute Withdrawal Assessment (CIWA) Scores	Proportion of clinical institute withdrawal assessment (CIWA) Scores listed as severe or moderate 24 Hours after Starting Study Drug. All subjects had at least four CIWA assessments.The CIWA is a ten item scale with each item on the scale scored independently on a 0-7 or 0-4 scale, and the summation of the scores yielding an aggregate value that correlates to the severity of alcohol withdrawal. Ranges of scores are from 0 to 67. Mild alcohol withdrawal is defined with a score less than or equal to 15, moderate with scores of 16 to 20, and severe with any score greater than 20. The ten items evaluated include nausea and vomiting, tremor, sweats, anxiety, agitation, tactile disturbances, auditory disturbances, visual disturbances, headache, and orientation.	Every 2-4 hours for 24 hours after starting study drug
The Occurrence of Adverse Events.	Occurrence of hypotension or bradycardia while on study drug	Seven days
Plasma Epinephrine Concentrations Across Groups Over Time	Plasma epinephrine concentrations	Four days with samples measured prior to study drug and 48 and 96 hours after starting study drug
Duration of Study Drug Administration		The duration of study drug in hours as measured when the subject was discharged from the ICU, for up to 24 weeks
ICU Length of Stay		The duration of ICU stay in days as measured at time of hospital discharge, for up to 24 weeks

Collaborators and Investigators

• Sponsor: University of Colorado, Denver
• Collaborators: Hospira, now a wholly owned subsidiary of Pfizer
• Investigators: Principal Investigator: Robert MacLaren, PharmD, University of Colorado School of Pharmacy

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: September 1, 2009
• Primary Completion (ACTUAL): October 1, 2012
• Study Completion (ACTUAL): October 1, 2012

Study Registration Dates

• First Submitted: July 8, 2009
• First Submitted That Met QC Criteria: July 9, 2009
• First Posted (ESTIMATE): July 10, 2009

Study Record Updates

• Last Update Posted (ESTIMATE): May 12, 2016
• Last Update Submitted That Met QC Criteria: April 7, 2016
• Last Verified: April 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Hypnotics and Sedatives; Dexmedetomidine
• Other Study ID Numbers: 09-0406