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

Information source: Denver Health and Hospital Authority
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Alcohol Withdrawal Delirium; Alcohol Withdrawal Associated Autonomic Hyperactivity; Alcohol Withdrawal Hallucinosis; Alcohol Withdrawal-Induced Delirium Tremens

Intervention: Dexmedetomidine (Drug); Placebo (Drug)

Phase: Phase 4

Status: Recruiting

Sponsored by: Denver Health and Hospital Authority

Official(s) and/or principal investigator(s):
Ivor S Douglas, MD, FRCP, Principal Investigator, Affiliation: Denver Health Medical Center

Overall contact:
Katie Overdier, BSc (Hons), Phone: 303-602-1479, Email: katie.overdier@dhha.org

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.

Clinical Details

Official title: A Randomized, Double-blind, Placebo-controlled, Parallel-group Study of Dexmedetomidine (Precedex«), With Lorazepam Rescue, for the Management of Severe Alcohol Withdrawal Syndrome (AWS) and Alcohol Withdrawal Delirium (AWD)

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Primary outcome: The length of ICU stay defined as the time between randomization and ICU transfer orders.

Secondary outcome:

The number of delirium-free and ventilator-free days during the first 28 days of hospitalization

The length in days of the hospital stay

Scores at hospital discharge on the Mini Mental Exam, Beck Depression Inventory, Beck Anxiety Inventory and PTSD checklist.

Resource utilization costs associated with this hospitalization.

Predefined adverse events

average MINDS score

Detailed description: Severe alcohol withdrawal syndrome (AWS) and alcohol withdrawal delirium (AWD) are frequent principal indication/s for admission to intensive care units. Additionally, unanticipated alcohol withdrawal complicates other critical illnesses and peri-operative states. Alcohol intoxication and withdrawal syndrome are characterized by classic symptoms of adrenergic activation, psychiatric agitation including seizures, as well as metabolic and respiratory dysfunction. The majority of patients with severe AWS are effectively managed with combinations of benzodiazepine (BZD) sedatives (e. g. lorazepam) and butyrophenone antipsychotics (e. g. haloperidol) and require intensive care admission for 2-3 days. However, almost 25% of patients with SAWS have a prolonged critical care course, often complicated by respiratory failure and associated with excessive sedation and risk for complications such as ventilator-associated pneumonia (VAP). AWS is frequently difficult to manage with usual care including benzodiazepines. Additionally, while intermittent bolus dose sedation is recommended for AWS, high dose BZD alone is associated with excessive respiratory suppression and metabolic acidosis. Such therapy increases the likelihood of respiratory failure with its attendant complications of hospital acquired pneumonia and sepsis. Further, patients with underlying chronic liver disease are at greater risk for prolonged sedative effects of BZD and progression of hepatic encephalopathy. The requirement for mechanical ventilation additionally prolongs the course of treatment for AWD because of the need for prolonged sedation. Strategies to control AWS/AWD that control symptoms but avoid adverse effects of excessive respiratory suppression are anticipated to improve the short and medium-term outcomes of AWS. BZD infusions have also been shown by several investigators to result in excessive and prolonged sedation. However, reasonable alternatives for effective control of psychomotor and adrenergic activation have until recently, been unavailable. The centrally acting alpha-2 receptor agonist, clonidine has been suggested as a useful adjunctive therapy to BZD. However, clonidine is only a mild sedative and can result in significant hemodynamic compromise. By contrast, dexmedetomidine (Precedex), a more potent alpha-2 receptor agonist, is potentially a more effective adjunctive therapy. Precedex is currently marketed in the USA for short-term use as a potent peri-operative sedative and analgesic. This agent has a short circulating half-life and has significantly fewer hemodynamic side effects than clonidine. In addition to its cardiovascular properties, dexmedetomidine possesses anxiolytic, hypnotic/sedative, anesthetic-sparing and analgesic actions and is devoid of significant respiratory depressant effects. Precedex has been shown to be a safe and effective single agent sedative for critically ill medical and surgical patients in prolonged infusions up to thirty days and is associated with significantly lower incidence of delirium than sedation with the benzodiazepine, midazolam. Preclinical experience and case reports suggest anecdotally Precedex may be of particular benefit in patients with SAWS. Measures of sedation and delirium will be assessed with the Minnesota Detoxification Scale (MINDS) derived for use in critically ill adults from the validated Clinical Institute Withdrawal Assessment (CIWA-r) scale.

Eligibility

Minimum age: 18 Years. Maximum age: 89 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- 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: 1. autonomic hyperactivity (e. g., sweating or pulse rate greater than 100) 2. increased hand tremor 3. insomnia 4. nausea or vomiting 5. transient visual, tactile, or auditory hallucinations or illusions 6. psychomotor agitation 7. anxiety 8. grand mal seizures

- The symptoms are not due to a general medical condition and are not better accounted

for by another mental disorder. AND Meets DSM-IV diagnostic criteria for 291. 0 Alcohol Intoxication or Withdrawal Delirium

- Disturbance of consciousness

- A change in cognition

- The disturbance develops over a short time and can fluctuate

- Onset is temporal associated with Alcohol Withdrawal Syndrome

Exclusion Criteria:

- 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

- Second- or third degree heart block

- Systolic blood pressure less than 90 mm Hg despite continuous infusions of 2

vasopressors before the start of study drug infusion.

- Previous randomization into this study.

Locations and Contacts

Katie Overdier, BSc (Hons), Phone: 303-602-1479, Email: katie.overdier@dhha.org

Memorial Hospital Central, Colorado Springs, Colorado 80909, United States; Recruiting
Ronald Rains, MD, Principal Investigator

Memorial Hospital North, Colorado Springs, Colorado 80920, United States; Recruiting
Ronald Rains, MD, Principal Investigator

Denver Health Medical Center, Medical ICU, Denver, Colorado 80204, United States; Recruiting

Porter Adventist Hospital, Denver, Colorado 80210, United States; Recruiting
Paula F Dennen, MD, Principal Investigator

St. Anthony Hospital, Lakewood, Colorado 80228, United States; Not yet recruiting
Paula F Dennen, MD, Principal Investigator

Louisiana State University, New Orleans, Louisiana 70112, United States; Recruiting
Bennett deBoisblanc, MD, Principal Investigator

Ben Taub Hospital, Houston, Texas 77030, United States; Recruiting
Philip Alapat, MD, Principal Investigator

Additional Information

Related publications:

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.

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.

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.

Maccioli GA. Dexmedetomidine to facilitate drug withdrawal. Anesthesiology. 2003 Feb;98(2):575-7.

Starting date: March 2012
Last updated: May 26, 2015

Page last updated: August 23, 2015

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