Treating Alcohol Withdrawal With Oral Baclofen - Full Text View

Sponsor:	Essentia Health
Information provided by:	Essentia Health
ClinicalTrials.gov Identifier:	NCT00597701

Purpose

The purpose of this study is determine if subjects with alcohol withdrawal who receive oral baclofen, plus standard benzodiazepine therapy, will experience less severe withdrawal symptoms than those who receive placebo plus standard benzodiazepine therapy.Subjects with alcohol withdrawal syndrome(AWS)who receive baclofen plus standard benzodiazepine therapy will experience fewer complications of AWS (as measured by use of additional sedatives, restraints, and/or intensive care unit [ICU] admissions) compared with subjects who receive placebo plus standard benzodiazepine therapy.

Condition	Intervention
Alcohol Withdrawal Delirium	Drug: Baclofen Drug: Placebo Drug: Lorazepam

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: Prevention
Official Title:	Treating Alcohol Withdrawal With Oral Baclofen: a Randomized, Double Blind, Placebo Controlled Trial

Resource links provided by NLM:

MedlinePlus related topics: Delirium

Drug Information available for: Ethanol Lorazepam Baclofen

U.S. FDA Resources

Further study details as provided by Essentia Health:

Primary Outcome Measures:

Benzodiazepine Doses Used to Treat Acutely-withdrawing Alcoholic Patients in the Baclofen-treated and Placebo-treated Groups [ Time Frame: From eligibility for randomization (Clinical Institute Withdrawal Assessment [CIWA] score of at least 11) until 72 hours of observation had been completed. ] [ Designated as safety issue: Yes ]
In acutely-withdrawing alcoholic patients treated with either baclofen or placebo, symptom-driven benzodiazepine doses were assessed for the 72 hours following the first Clinical Institute Withdrawal Assessment (CIWA) score of 11 or greater.

Enrollment:	79
Study Start Date:	April 2003
Study Completion Date:	February 2008
Primary Completion Date:	February 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: Baclofen Standard benzodiazepine therapy plus baclofen 10 mg every 8 hours for 72 hours (9 doses) as an inpatient, or until discharge if before 72 hours.	Drug: Baclofen Baclofen 10 mg by mouth every 8 hours for 72 hours or until discharge if before 72 hours. Other Name: Lioresal Drug: Lorazepam Lorazepam was provided to all subjects (both arms of the study), as indicated by clinical condition. Standard "symptom-triggered dosing" of lorazepam for alcohol withdrawal was used. That is, the size and the frequency of the dose of lorazepam was determined by the severity of the alcohol withdrawal symptoms.
Placebo Comparator: Placebo Standard benzodiazepine therapy plus placebo every eight hous as inpatients for 72 hours or until discharge if less than 72 hours.	Drug: Placebo Placebo Drug: Lorazepam Lorazepam was provided to all subjects (both arms of the study), as indicated by clinical condition. Standard "symptom-triggered dosing" of lorazepam for alcohol withdrawal was used. That is, the size and the frequency of the dose of lorazepam was determined by the severity of the alcohol withdrawal symptoms.

Arms

Assigned Interventions

Active Comparator: Baclofen

Standard benzodiazepine therapy plus baclofen 10 mg every 8 hours for 72 hours (9 doses) as an inpatient, or until discharge if before 72 hours.

Drug: Baclofen

Baclofen 10 mg by mouth every 8 hours for 72 hours or until discharge if before 72 hours.

Other Name: Lioresal

Drug: Lorazepam

Lorazepam was provided to all subjects (both arms of the study), as indicated by clinical condition. Standard "symptom-triggered dosing" of lorazepam for alcohol withdrawal was used. That is, the size and the frequency of the dose of lorazepam was determined by the severity of the alcohol withdrawal symptoms.

Placebo Comparator: Placebo

Standard benzodiazepine therapy plus placebo every eight hous as inpatients for 72 hours or until discharge if less than 72 hours.

Drug: Placebo

Placebo

Drug: Lorazepam

Lorazepam was provided to all subjects (both arms of the study), as indicated by clinical condition. Standard "symptom-triggered dosing" of lorazepam for alcohol withdrawal was used. That is, the size and the frequency of the dose of lorazepam was determined by the severity of the alcohol withdrawal symptoms.

Detailed Description:

Alcohol use is ubiquitous in American society. 83% of Americans have ever consumed alcohol, 51% have in the lst month.

The average American consumes 2.18 gallons of ethanol yearly. Alcohol related morbidity and mortality are staggering problems in the USA. Symptoms of alcohol withdrawal occur because alcohol is a central nervous system depressant; abrupt withdrawal unmasks compensatory overactivity of certain parts of the nervous system, including sympathetic autonomic outflow. 5% of patients who undergo alcohol suffer from Delirium Tremors (DTs), a syndrome characterized by hallucinations, disorientation, tachycardia, hypertension, low grade fever, agitation, and diaphoresis.

DTs typically begin between 48-96 hours after the last drink and last 1 to 5 days. DTs requires hospitalization and vigorous activity in an ICU setting.

The most successful drug treatment for alcohol withdrawal has been found to be the benzodiazepines.

Symptom triggered treatment was found to be as effective as a fixed dose treatment to result in less drug being used overall, with a trend toward shorter duration of withdrawal treatment.

Baclofen is used orally for the treatment of spasticity resulting from multiple sclerosis, spinal cord injuries/diseases and intrathecally for spasticity related to cerebral palsy, spinal cord injury, and amyotrophic lateral sclerosis (ALS).

Its proposed benefit in alcohol withdrawal is that it may reduce voluntary alcohol intake, alcohol craving, and may suppress the intensity of alcohol withdrawal treatment.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Meet Diagnostic and Statistical Manual, 4th version, revised (DSMr-IV) criteria for alcohol withdrawal syndrome (AWS).
Be an inpatient at St. Mary's Medical Center (SMMC) or Miller Dwan Medical Center (MDMC) at time of study enrollment.
Have an alcohol withdrawal score as measured by standard SMMC or MDMC inpatient protocol sufficient to trigger the use of benzodiazepine withdrawal therapy.
Agree to abstain for alcohol for duration of study.
Be able to provide informed consent.

Exclusion Criteria:

The patient must not have any other active drug dependence in addition to alcohol.
Be unwilling or unable to forgo alcohol for the duration of the study.
Be using baclofen at the time of study enrollment.
Be using benzodiazepines for any reason other than acute alcohol withdrawal syndrome at time of study enrollment.
have known baclofen or benzodiazepine sensitivity.
Be unable to take oral (PO) meds.
Be unable to complete one of two consenting procedures.
Be pregnant or breastfeeding.
Have a serum creatine level > 2.0.
Have a history of non alcoholic withdrawal seizures.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00597701

Locations

United States, Minnesota
Essentia Health
Duluth, Minnesota, United States, 55805

Sponsors and Collaborators

Essentia Health

Investigators

Principal Investigator:

Jeffrey Lyon, MD

Essentia Health

More Information

Publications:

Colombo G, Agabio R, Carai MA, Lobina C, Pani M, Reali R, Addolorato G, Gessa GL. Ability of baclofen in reducing alcohol intake and withdrawal severity: I--Preclinical evidence. Alcohol Clin Exp Res. 2000 Jan;24(1):58-66.

Addolorato G, Caputo F, Capristo E, Janiri L, Bernardi M, Agabio R, Colombo G, Gessa GL, Gasbarrini G. Rapid suppression of alcohol withdrawal syndrome by baclofen. Am J Med. 2002 Feb 15;112(3):226-9. No abstract available.

Responsible Party:	Jeffrey Lyon, MD, Essentia Health
ClinicalTrials.gov Identifier:	NCT00597701 History of Changes
Other Study ID Numbers:	090403
Study First Received:	January 9, 2008
Results First Received:	June 29, 2011
Last Updated:	July 25, 2011
Health Authority:	United States: Institutional Review Board

Keywords provided by Essentia Health:

Alcohol withdrawal
Delirium tremors

Additional relevant MeSH terms:

Alcohol Withdrawal Delirium
Delirium
Alcohol-Induced Disorders, Nervous System
Neurotoxicity Syndromes
Nervous System Diseases
Alcohol-Induced Disorders
Alcohol-Related Disorders
Substance-Related Disorders
Poisoning
Substance Withdrawal Syndrome
Mental Disorders
Confusion
Neurobehavioral Manifestations
Neurologic Manifestations
Signs and Symptoms

Delirium, Dementia, Amnestic, Cognitive Disorders
Ethanol
Lorazepam
Baclofen
Anti-Infective Agents, Local
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Central Nervous System Depressants
Physiological Effects of Drugs
Central Nervous System Agents
GABA-B Receptor Agonists
GABA Agonists
GABA Agents
Neurotransmitter Agents

ClinicalTrials.gov processed this record on February 09, 2012