Preventing Alcohol Withdrawal Syndrome With Oral Baclofen

• Sponsor: Denver Health and Hospital Authority (Other)
• Overall Status: Terminated
• CT.gov ID: NCT02052440
• Collaborator: (none)
• Enrollment: 102
• Location: 1
• Arms: 2
• Duration (Months): 33.6
• Patients Per Site Per Month: 3

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Alcohol Withdrawal Syndrome	Drug: Baclofen; Drug: Placebo	Phase 3

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 Design

• Study Type: Interventional
• Actual Enrollment: 102 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Preventing Alcohol Withdrawal Syndrome With Oral Baclofen: A Randomized, Placebo Controlled Trial
• Study Start Date: Mar 15, 2014
• Actual Primary Completion Date: Jan 1, 2017
• Actual Study Completion Date: Jan 1, 2017

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Prevention of Progression to Severe Alcohol Withdrawal as Assessed by Severity of Ethanol Withdrawal Score (SEWS). [Within 72 hours]

   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.

Secondary Outcome Measures

1. Reduced Severity of Alcohol Withdrawal as Measured by Severity of Ethanol Withdrawal Score. . [Over 72 hours]

   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.

2. Difference in Maximal Dose of Ethanol Withdrawal Symptom Driven Benzodiazepine Administration, as Assessed by SEWS Score, in Treatment Group When Compared to Placebo Group [72 hours]

   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.

3. Difference in Cumulative Dose of Ethanol Withdrawal Symptom Driven Benzodiazepine Administration, as Assessed by SEWS Score, in Treatment Group Compared With Placebo Group. [72 hours]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Denver Health Hospital	Denver	Colorado	United States	80204

Sponsors and Collaborators

• Denver Health and Hospital Authority

Investigators

• Principal Investigator: Daniel B Heppe, MD, Denver Health

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Denver Health and Hospital Authority
• ClinicalTrials.gov Identifier: NCT02052440
• Other Study ID Numbers: 13-2883
• First Posted: Feb 3, 2014
• Last Update Posted: May 23, 2018
• Last Verified: Apr 1, 2018

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Additional relevant MeSH terms: Syndrome; Substance Withdrawal Syndrome; Baclofen

Study Results

Participant Flow

Recruitment Details	Recruitment and enrollment began March 1 2014 and terminated Jan 1 2017. Patients were enrolled after admission to general medical services at Denver Health Hospital.
Pre-assignment Detail	Patients could be excluded if found to be pregnant prior to being assigned to study arm.

Arm/Group Title	Baclofen 10mg Three Times Daily	Sugar Pill Given Three Times Daily
Arm/Group Description	Baclofen 10mg by mouth three times daily Baclofen: Treatment arm: baclofen 10mg tid	Placebo sugar bill Placebo: Sugar pill by mouth three times daily
Period Title: Overall Study
STARTED	50	52
COMPLETED	50	51
NOT COMPLETED	0	1

Baseline Characteristics

Arm/Group Title	Baclofen 10mg Three Times Daily	Sugar Pill Given Three Times Daily	Total
Arm/Group Description	Baclofen 10mg by mouth three times daily Baclofen: Treatment arm: baclofen 10mg tid	Placebo sugar bill Placebo: Sugar pill by mouth three times daily	Total of all reporting groups
Overall Participants	50	51	101
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	50 (10)	51 (11)	50 (10)
Sex: Female, Male (Count of Participants)
Female	9 18%	13 25.5%	22 21.8%
Male	41 82%	38 74.5%	79 78.2%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	4 8%	3 5.9%	7 6.9%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	4 8%	7 13.7%	11 10.9%
White	41 82%	41 80.4%	82 81.2%
More than one race	1 2%	0 0%	1 1%
Unknown or Not Reported	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Prevention of Progression to Severe Alcohol Withdrawal as Assessed by Severity of Ethanol Withdrawal Score (SEWS).
Description	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.
Time Frame	Within 72 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Baclofen 10mg Three Times Daily	Sugar Pill Given Three Times Daily
Arm/Group Description	Baclofen 10mg by mouth three times daily Baclofen: Treatment arm: baclofen 10mg tid	Placebo sugar bill Placebo: Sugar pill by mouth three times daily
Measure Participants	50	51
Count of Participants [Participants]	13 26%	16 31.4%

2. Secondary Outcome

Title	Reduced Severity of Alcohol Withdrawal as Measured by Severity of Ethanol Withdrawal Score. .
Description	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.
Time Frame	Over 72 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Baclofen 10mg Three Times Daily	Sugar Pill Given Three Times Daily
Arm/Group Description	Baclofen 10mg by mouth three times daily Baclofen: Treatment arm: baclofen 10mg tid	Placebo sugar bill Placebo: Sugar pill by mouth three times daily
Measure Participants	50	51
Highest SEWS score at 24 hours	6 (4)	6 (4)
Highest SEWS score at 48 hours	4 (3)	4 (4)
Highest SEWS score at 72 hours	2 (3)	3 (3)

3. Secondary Outcome

Title	Difference in Maximal Dose of Ethanol Withdrawal Symptom Driven Benzodiazepine Administration, as Assessed by SEWS Score, in Treatment Group When Compared to Placebo Group
Description	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.
Time Frame	72 hours

Outcome Measure Data

Analysis Population Description

Maximum dose of symptom driven benzodiazepine

Arm/Group Title	Baclofen 10mg Three Times Daily	Sugar Pill Given Three Times Daily
Arm/Group Description	Baclofen 10mg by mouth three times daily Baclofen: Treatment arm: baclofen 10mg tid	Placebo sugar bill Placebo: Sugar pill by mouth three times daily
Measure Participants	50	51
Mean (Standard Deviation) [Milligram of Diazepam]	11 (2)	12 (7)

4. Secondary Outcome

Title	Difference in Cumulative Dose of Ethanol Withdrawal Symptom Driven Benzodiazepine Administration, as Assessed by SEWS Score, in Treatment Group Compared With Placebo Group.
Description	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.
Time Frame	72 hours

Outcome Measure Data

Analysis Population Description

Cumulative dose of symptom driven benzodiazepine

Arm/Group Title	Baclofen 10mg Three Times Daily	Sugar Pill Given Three Times Daily
Arm/Group Description	Baclofen 10mg by mouth three times daily Baclofen: Treatment arm: baclofen 10mg tid	Placebo sugar bill Placebo: Sugar pill by mouth three times daily
Measure Participants	50	51
Mean (Standard Deviation) [Milligram of Diazepam]	66 (51)	85 (63)

Adverse Events

Time Frame	While subject inpatient and enrolled in study until time of discharge or maximum 96 hours, whichever came first.
Adverse Event Reporting Description	Study personnel checked with nursing and treatment teams daily to monitor for adverse events
Arm/Group Title	Baclofen 10mg Three Times Daily		Sugar Pill Given Three Times Daily
Arm/Group Description	Baclofen 10mg by mouth three times daily Baclofen: Treatment arm: baclofen 10mg tid		Placebo sugar bill Placebo: Sugar pill by mouth three times daily
All Cause Mortality
	Baclofen 10mg Three Times Daily		Sugar Pill Given Three Times Daily
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/50 (0%)		0/51 (0%)
Serious Adverse Events
	Baclofen 10mg Three Times Daily		Sugar Pill Given Three Times Daily
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/50 (0%)		0/51 (0%)
Other (Not Including Serious) Adverse Events
	Baclofen 10mg Three Times Daily		Sugar Pill Given Three Times Daily
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/50 (2%)		0/51 (0%)
Skin and subcutaneous tissue disorders
Rash	1/50 (2%)	1	0/51 (0%)	0

Limitations/Caveats

The number of patients enrolled was less than was needed based on our sample size estimation due to termination of study secondary to funding limitations. This study was performed at a single, university-affiliated public safety net hospital.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.