Dexmedetomidine (Precedex®) for Severe Alcohol Withdrawal Syndrome (AWS) and Alcohol Withdrawal Delirium (AWD)

NCT01362205 | Terminated Phase 4 Results DMC

• 1 other identifier: COMIRB 09-0822
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 7

Brief Summary

This is a prospective, randomized, double-blind, placebo-controlled, parallel-group study of dexmedetomidine versus placebo, with lorazepam rescue, for the management of severe alcohol withdrawal syndrome (AWS) and alcohol withdrawal delirium (AWD) in critically ill adults. The investigators hypothesize that the integration of dexmedetomidine (Precedex®) with usual therapy for the management of severe alcohol withdrawal syndrome (AWS) and alcohol withdrawal delirium/delirium tremens (AWD) in critically ill adult patients will reduce the time to resolution of AWS/AWD, increase the number of delirium-free and ventilator-free days in the first 28 days of hospitalization, reduce the length of ICU and hospital stays, and improve neurocognitive and quality of life scores on hospital discharge.

Conditions

Alcohol Withdrawal Delirium; Alcohol Withdrawal Associated Autonomic Hyperactivity; Alcohol Withdrawal Hallucinosis; Alcohol Withdrawal-Induced Delirium Tremens

Keywords

Severe Alcohol Withdrawal Delirium Tremens

Outcome Measures

Primary Outcomes (1)

• The Length of ICU Stay Defined as the Time Between Randomization and ICU Transfer Orders.

  up to 28 days in hours

Secondary Outcomes (10)

• Average MINDS Score

  up to 28 days

• The Number of CAM-ICU Negative Days After Randomization.

  up to 28 days

• Number of Ventilator Free Days After Randomization.

  up to 28 days

• The Length in Days of the Hospital Stay

  up to 28 days

• Scores at Hospital Discharge on the Mini Mental Exam.

  up to 28 days

Study Arms (2)

Dexmedetomidine

EXPERIMENTAL

Dexmedetomidine titrated to achieve predefined goals on selected components of the MINDS score using the minimum amount of medication possible. Blinded study medication will be started at a rate determined by the MINDS score. The maximum infusion rate is 1.4 μg/kg per hour. Uncontrolled SAWS/D symptoms, will be treated with open label lorazepam according to the MINDS score algorithm. Persistent SAWS/D symptoms despite maximum infusion rate of study medication treatment limiting symptoms while receiving higher infusion rates of study medication, ancillary therapies will be administered according to the MINDS score algorithm, at the discretion of the treating physician.

Drug: Dexmedetomidine

Placebo

PLACEBO COMPARATOR

Blinded placebo study drug administration in equal volume per hour as active study medication arm.

Drug: Placebos

Interventions

Dexmedetomidine DRUG

Also known as: Precedex

Dexmedetomidine

Placebos DRUG

Inactive placebo (normal saline)

Placebo

Eligibility Criteria

• Age: 18 Years - 89 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients, 18 years or older, with severe AWS or AWD per DSM-IV definitions (below) requiring admission to the ICU for medical management
• Ability to provide informed consent (via a proxy decision maker or patient).
• Within 96 hours of ICU admission.
• Meets DSM-IV diagnostic criteria for 291.8 Alcohol Withdrawal Syndrome:
• Cessation of (or reduction in) alcohol use that has been heavy and prolonged.
• Two (or more) of the following, developing within several hours to a few days after Criterion A:
• autonomic hyperactivity (e.g., sweating or pulse rate greater than 100)
• increased hand tremor
• insomnia
• nausea or vomiting
• transient visual, tactile, or auditory hallucinations or illusions
• psychomotor agitation
• anxiety
• grand mal seizures
• The symptoms are not due to a general medical condition and are not better accounted for by another mental disorder.

You may not qualify if:

• Age \< 18 years
• Physician anticipates ICU transfer orders in less than 12 hours from time of consent.
• Recent traumatic brain injury
• Active status epilepticus
• Pregnancy or lactation
• Known allergy or adverse response to any of the study medications
• Requiring glucocorticoid therapy for treatment of acute hepatitis or Stage III (advanced) decompensated liver failure and encephalopathy
• Trauma or burns as admitting diagnoses
• Neuromuscular blockade other than for intubation
• Epidural or spinal analgesia
• General anesthesia 24 hours prior to, or planned after, the start of study drug infusion
• Serious central nervous system pathology (acute stroke, uncontrolled seizures, severe dementia),
• Unstable angina or acute myocardial infarction
• Left ventricular ejection fraction less than 30%
• Heart rate less than 50/min

Sponsors & Collaborators

• Denver Health and Hospital Authority: lead

Study Sites (7)

Memorial Hospital Central

Colorado Springs, Colorado, 80909, United States

Location

Memorial Hospital North

Colorado Springs, Colorado, 80920, United States

Location

Denver Health Medical Center, Medical ICU

Denver, Colorado, 80204, United States

Location

Porter Adventist Hospital

Denver, Colorado, 80210, United States

Location

St. Anthony Hospital

Lakewood, Colorado, 80228, United States

Location

Louisiana State University

New Orleans, Louisiana, 70112, United States

Location

Ben Taub Hospital

Houston, Texas, 77030, United States

Location

Related Publications (4)

• Riker RR, Shehabi Y, Bokesch PM, Ceraso D, Wisemandle W, Koura F, Whitten P, Margolis BD, Byrne DW, Ely EW, Rocha MG; SEDCOM (Safety and Efficacy of Dexmedetomidine Compared With Midazolam) Study Group. Dexmedetomidine vs midazolam for sedation of critically ill patients: a randomized trial. JAMA. 2009 Feb 4;301(5):489-99. doi: 10.1001/jama.2009.56. Epub 2009 Feb 2.

  PMID: 19188334 BACKGROUND

• Darrouj J, Puri N, Prince E, Lomonaco A, Spevetz A, Gerber DR. Dexmedetomidine infusion as adjunctive therapy to benzodiazepines for acute alcohol withdrawal. Ann Pharmacother. 2008 Nov;42(11):1703-5. doi: 10.1345/aph.1K678. Epub 2008 Sep 9.

  PMID: 18780809 BACKGROUND

• Rovasalo A, Tohmo H, Aantaa R, Kettunen E, Palojoki R. Dexmedetomidine as an adjuvant in the treatment of alcohol withdrawal delirium: a case report. Gen Hosp Psychiatry. 2006 Jul-Aug;28(4):362-3. doi: 10.1016/j.genhosppsych.2006.03.002.

  PMID: 16814639 BACKGROUND

• Maccioli GA. Dexmedetomidine to facilitate drug withdrawal. Anesthesiology. 2003 Feb;98(2):575-7. doi: 10.1097/00000542-200302000-00041. No abstract available.

  PMID: 12552220 BACKGROUND

MeSH Terms

Conditions

Alcohol Withdrawal Delirium

Interventions

Dexmedetomidine

Condition Hierarchy (Ancestors)

Alcohol-Induced Disorders, Nervous System; Neurotoxicity Syndromes; Nervous System Diseases; Poisoning; Chemically-Induced Disorders; Alcohol-Induced Disorders; Alcohol-Related Disorders; Substance-Related Disorders; Substance Withdrawal Syndrome; Mental Disorders

Intervention Hierarchy (Ancestors)

Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Limitations and Caveats

Early termination due to slow enrollment leading to small numbers of subjects analyzed

Results Point of Contact

• Title: Katie Overdier RN
• Organization: Denver Health Medical Center

Katie.Overdier@dhha.org

303 602 1479

Study Officials

• Ivor S Douglas, MD, FRCP

  Denver Health Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: May 24, 2010
• First Posted: May 30, 2011
• Study Start: March 1, 2012
• Primary Completion: December 1, 2015
• Study Completion: September 1, 2016
• Last Updated: November 6, 2017
• Results First Posted: July 17, 2017

Record last verified: 2017-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (7)