Clinical trial NCT00936377: Dexmedetomidine as Adjunctive Therapy for Alcohol Withdrawal
Official title: A Randomized, Double-Blind, Placebo Controlled, Dose Escalation Study of Dexmedetomidine as Adjunctive Therapy for Alcohol Withdrawal
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Acute Alcohol Withdrawal
Lead sponsor: University of Colorado, Denver
Sponsor class: OTHER
Collaborators: name: Hospira, now a wholly owned subsidiary of Pfizer
First posted: 2009-07-10
Enrollment: 24
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 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.

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

Primary outcomes:
measure: Cumulative Lorazepam Dose Over the First Seven Days of Alcohol Withdrawal
timeFrame: Seven days
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
Secondary outcomes:
measure: The Degree of Alcohol Withdrawal Assessed by Clinical Institute Withdrawal Assessment (CIWA) Scores
timeFrame: Every 2-4 hours for 24 hours after starting study drug
measure: The Occurrence of Adverse Events.
timeFrame: Seven days
measure: Plasma Epinephrine Concentrations Across Groups Over Time
timeFrame: Four days with samples measured prior to study drug and 48 and 96 hours after starting study drug
measure: Duration of Study Drug Administration
timeFrame: The duration of study drug in hours as measured when the subject was discharged from the ICU, for up to 24 weeks
measure: ICU Length of Stay
timeFrame: The duration of ICU stay in days as measured at time of hospital discharge, for up to 24 weeks
Other outcomes:
Locations:
city: Aurora
country: United States
facility: University of Colorado Hospital
state: Colorado
Study officials:
affiliation: University of Colorado School of Pharmacy
name: Robert MacLaren, PharmD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.