Preventing Alcohol Withdrawal Syndrome With Oral Baclofen

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Alcohol Withdrawal Syndrome

Intervention / Treatment
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* Drug: Baclofen
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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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 |