Preventing Alcohol Withdrawal Syndrome With Oral Baclofen

Preventing Alcohol Withdrawal Syndrome With Oral Baclofen: A Randomized, Placebo Controlled Trial

Adult medical/surgical inpatient hospital care is more difficult and more expensive when complicated by alcohol dependency (AD), especially for patients who develop alcohol withdrawal syndrome (AWS). AWS can be mild, moderate or severe. The Severity of Ethanol Withdrawal Scale (SEWS) is tool used to assess severity and is the current standard of care for both monitoring and treating AWS at Denver Health. Moderate/severe AWS (i.e., SEWS ≥ 7) has important clinical implications and requires pharmacological treatment. At present, there are no safe and effective options for preventing AWS in at-risk inpatients. Baclofen is a GABA-B receptor agonist that has been used in the alleviation of spasticity in patients with multiple sclerosis since the 1970s. Baclofen has shown promise in the management of alcohol dependency in preclinical and clinical studies. We propose to examine baclofen in the prevention/amelioration of AWS in adult medical inpatients. The investigators hypothesize that Baclofen, as compared to placebo, will significantly reduce the number of adult inpatients with AD who will develop moderate/severe AWS (SEWS ≥ 7) when assessed at 72 hours after enrollment. Further the investigators hypothesize that Baclofen, as compared to placebo, will significantly reduce the need for symptom-triggered benzodiazepine administration during the 72 hours of hospitalization. These hypotheses will be tested in adult inpatients who are determined to be at risk for alcohol withdrawal and are subsequently placed on the SEWS monitoring and treatment protocol. These patients will be randomized to baclofen 10mg three times daily vs placebo.

Study Overview

• Status: Terminated
• Conditions: Alcohol Withdrawal Syndrome
• Intervention / Treatment: Drug: Baclofen; Drug: Placebo

Detailed Description

See Brief Summary. Patients will recieve standard of Care treatment and monitoring for ETOH withdrawl per our insitution wide SEWS protocol. They will then be randomized to recieve baclofen 10mg tid vs placebo tid for the course of their hospital stay or 7 days, whichever comes first.

• Study Type: Interventional
• Enrollment (Actual): 102
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Denver, Colorado, United States, 80204
      • Denver Health Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adults age 21-100 admitted to medical floors at Denver Health
• Patients placed on SEWS protocol by admitting physicians (at risk for AWS).

Exclusion Criteria:

• Unable to provide informed consent
• Unable to take oral medications
• admitted for AWS or with SEWS score >7 at baseline
• no alcohol intake for ≥ 48 hours
• baclofen use at baseline
• baclofen sensitivity
• hospital discharge anticipated in within 48 hours
• pregnant or breast feeding (urine pregnancy test required of women of child-bearing potential
• other active drug dependence (except tobacco)
• taking a medication known to interact with baclofen.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Baclofen 10mg three times daily; Baclofen 10mg by mouth three times daily	Drug: Baclofen; Treatment arm: baclofen 10mg tid; Other Names: Baclofen 10mg will be given three times daily
Placebo Comparator: Sugar Pill given three times daily; Placebo sugar bill	Drug: Placebo; Sugar pill by mouth three times daily; Other Names: Sugar pill

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prevention of Progression to Severe Alcohol Withdrawal as Assessed by Severity of Ethanol Withdrawal Score (SEWS).	Prevention of progression to Severe Alcohol withdrawal as assessed by Severity of Ethanol Withdrawal Score (SEWS). A score of > 7 represents moderate alcohol withdrawal and a score > 12 severe alcohol withdrawal. Reported below as number of patients in each group progressing to moderate or severe alcohol withdrawal as assessed by SEWS score.	Within 72 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reduced Severity of Alcohol Withdrawal as Measured by Severity of Ethanol Withdrawal Score. .	Severity of alcholol withdrawal will be assessed by monitoring SEWS scores in both baclofen and placebo group. This score is reported as a cumulative unit on scale ranging from 0 to 23. A value of 1-6 represents mild alcohol withdrawal, 7-12 moderate and >12 severe. Values will be measured 24 hours, 48 hours and 72 hours. A mean of these values was calculated.	Over 72 hours
Difference in Maximal Dose of Ethanol Withdrawal Symptom Driven Benzodiazepine Administration, as Assessed by SEWS Score, in Treatment Group When Compared to Placebo Group	The null hypotheses of no difference in the maximum dose of inpatient symptom-triggered benzodiazepine therapy during the 72 hours following enrollment between those who receive baclofen and those who receive placebo. All maximum doses for each treatment arm given anytime between 0 and 72 hours were recorded and a mean calculated for each treatment arm.	72 hours
Difference in Cumulative Dose of Ethanol Withdrawal Symptom Driven Benzodiazepine Administration, as Assessed by SEWS Score, in Treatment Group Compared With Placebo Group.	The null hypotheses of no difference in the cumulative inpatient dosages of symptom-triggered benzodiazepine therapy during the 72 hours following enrollment between those who receive baclofen and those who receive placebo. Total benzodiazepine administration received from 0 to 72 hours was summed for each patient in each arm. A mean of this cumulative dose was then calculated for each arm and is reported below.	72 hours

Collaborators and Investigators

• Sponsor: Denver Health and Hospital Authority
• Investigators: Principal Investigator: Daniel B Heppe, MD, Denver Health

Study record dates

Study Major Dates

• Study Start: March 15, 2014
• Primary Completion (Actual): January 1, 2017
• Study Completion (Actual): January 1, 2017

Study Registration Dates

• First Submitted: January 30, 2014
• First Submitted That Met QC Criteria: January 31, 2014
• First Posted (Estimate): February 3, 2014

Study Record Updates

• Last Update Posted (Actual): May 23, 2018
• Last Update Submitted That Met QC Criteria: April 25, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Pathologic Processes; Substance-Related Disorders; Disease; Syndrome; Substance Withdrawal Syndrome; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; GABA Agents; Neuromuscular Agents; Muscle Relaxants, Central; GABA Agonists; GABA-B Receptor Agonists; Baclofen
• Other Study ID Numbers: 13-2883

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: No plan to share individual patient data