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Dexmedetomidine as Adjunctive Therapy for Alcohol Withdrawal (DATA)

This study has been completed.
Sponsor:
Collaborator:
Hospira, Inc.
Information provided by (Responsible Party):
University of Colorado, Denver
ClinicalTrials.gov Identifier:
NCT00936377
First received: July 8, 2009
Last updated: April 7, 2016
Last verified: April 2016
  Purpose
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.

Condition Intervention
Acute Alcohol Withdrawal
Drug: Dexmedetomidine
Other: Placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blind, Placebo Controlled, Dose Escalation Study of Dexmedetomidine as Adjunctive Therapy for Alcohol Withdrawal

Resource links provided by NLM:


Further study details as provided by University of Colorado, Denver:

Primary Outcome Measures:
  • Cumulative Lorazepam Dose Over the First Seven Days of Alcohol Withdrawal [ Time Frame: Seven days ] [ Designated as safety issue: No ]
  • Change in 12-Hour Lorazepam Requirement Pre- and Post-Treatment [ Time Frame: 12 hours before treatment, 12 hours after treatment on first day of starting study drug ] [ Designated as safety issue: No ]
  • Change in 24-Hour Lorazepam Requirement Pre- and Post-Treatment [ Time Frame: 24 hours before treatment, 24 hours after treatment on first day of starting study drug ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • The Degree of Alcohol Withdrawal Assessed by Clinical Institute Withdrawal Assessment (CIWA) Scores [ Time Frame: Every 2-4 hours for 24 hours after starting study drug ] [ Designated as safety issue: No ]
    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.

  • The Occurrence of Adverse Events. [ Time Frame: Seven days ] [ Designated as safety issue: Yes ]
    Occurrence of hypotension or bradycardia while on study drug

  • Plasma Epinephrine Concentrations Across Groups Over Time [ Time Frame: Four days with samples measured prior to study drug and 48 and 96 hours after starting study drug ] [ Designated as safety issue: No ]
    Plasma epinephrine concentrations

  • Duration of Study Drug Administration [ Time Frame: The duration of study drug in hours as measured when the subject was discharged from the ICU, for up to 24 weeks ] [ Designated as safety issue: No ]
  • ICU Length of Stay [ Time Frame: The duration of ICU stay in days as measured at time of hospital discharge, for up to 24 weeks ] [ Designated as safety issue: No ]

Enrollment: 24
Study Start Date: September 2009
Study Completion Date: October 2012
Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: Precedex
Placebo Comparator: Placebo
Normal saline
Other: Placebo
Normal saline for five days.

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

Ages Eligible for Study:   18 Years to 85 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00936377

Locations
United States, Colorado
University of Colorado Hospital
Aurora, Colorado, United States, 80045
Sponsors and Collaborators
University of Colorado, Denver
Hospira, Inc.
Investigators
Principal Investigator: Robert MacLaren, PharmD University of Colorado School of Pharmacy
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: University of Colorado, Denver
ClinicalTrials.gov Identifier: NCT00936377     History of Changes
Other Study ID Numbers: 09-0406 
Study First Received: July 8, 2009
Results First Received: March 9, 2016
Last Updated: April 7, 2016
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Dexmedetomidine
Hypnotics and Sedatives
Central Nervous System Depressants
Physiological Effects of Drugs
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Adrenergic alpha-2 Receptor Agonists
Adrenergic alpha-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on December 09, 2016