Alcohol Withdrawal Syndrome
Conditions
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.
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.
Interventions
DRUGBaclofen
Treatment arm: baclofen 10mg tid
DRUGPlacebo
Sugar pill by mouth three times daily
Sponsors
Denver Health and Hospital Authority
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
21 Years to No maximum
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
Countries
United States
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 details
Patients could be excluded if found to be pregnant prior to being assigned to study arm.
Participants by arm
| Arm | Count |
|---|---|
| Baclofen 10mg Three Times Daily Baclofen 10mg by mouth three times daily
Baclofen: Treatment arm: baclofen 10mg tid | 50 |
| Sugar Pill Given Three Times Daily Placebo sugar bill
Placebo: Sugar pill by mouth three times daily | 51 |
| Total | 101 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Sugar Pill Given Three Times Daily | Total | Baclofen 10mg Three Times Daily |
|---|---|---|---|
| Age, Continuous | 51 Years STANDARD_DEVIATION 11 | 50 Years STANDARD_DEVIATION 10 | 50 Years STANDARD_DEVIATION 10 |
| Race (NIH/OMB) American Indian or Alaska Native | 3 Participants | 7 Participants | 4 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants | 11 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 41 Participants | 82 Participants | 41 Participants |
| Sex: Female, Male Female | 13 Participants | 22 Participants | 9 Participants |
| Sex: Female, Male Male | 38 Participants | 79 Participants | 41 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 50 | 0 / 51 |
| other Total, other adverse events | 1 / 50 | 0 / 51 |
| serious Total, serious adverse events | 0 / 50 | 0 / 51 |
Outcome results
Primary
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.
Time frame: Within 72 hours
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Baclofen 10mg Three Times Daily | Prevention of Progression to Severe Alcohol Withdrawal as Assessed by Severity of Ethanol Withdrawal Score (SEWS). | 13 Participants |
| Sugar Pill Given Three Times Daily | Prevention of Progression to Severe Alcohol Withdrawal as Assessed by Severity of Ethanol Withdrawal Score (SEWS). | 16 Participants |
Secondary
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.
Time frame: 72 hours
Population: Cumulative dose of symptom driven benzodiazepine
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Baclofen 10mg Three Times Daily | Difference in Cumulative Dose of Ethanol Withdrawal Symptom Driven Benzodiazepine Administration, as Assessed by SEWS Score, in Treatment Group Compared With Placebo Group. | 66 Milligram of Diazepam | Standard Deviation 51 |
| Sugar Pill Given Three Times Daily | Difference in Cumulative Dose of Ethanol Withdrawal Symptom Driven Benzodiazepine Administration, as Assessed by SEWS Score, in Treatment Group Compared With Placebo Group. | 85 Milligram of Diazepam | Standard Deviation 63 |
Secondary
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.
Time frame: 72 hours
Population: Maximum dose of symptom driven benzodiazepine
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Baclofen 10mg Three Times Daily | Difference in Maximal Dose of Ethanol Withdrawal Symptom Driven Benzodiazepine Administration, as Assessed by SEWS Score, in Treatment Group When Compared to Placebo Group | 11 Milligram of Diazepam | Standard Deviation 2 |
| Sugar Pill Given Three Times Daily | Difference in Maximal Dose of Ethanol Withdrawal Symptom Driven Benzodiazepine Administration, as Assessed by SEWS Score, in Treatment Group When Compared to Placebo Group | 12 Milligram of Diazepam | Standard Deviation 7 |
Secondary
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.
Time frame: Over 72 hours
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Baclofen 10mg Three Times Daily | Reduced Severity of Alcohol Withdrawal as Measured by Severity of Ethanol Withdrawal Score. . | Highest SEWS score at 24 hours | 6 Unit on Scale | Standard Deviation 4 |
| Baclofen 10mg Three Times Daily | Reduced Severity of Alcohol Withdrawal as Measured by Severity of Ethanol Withdrawal Score. . | Highest SEWS score at 48 hours | 4 Unit on Scale | Standard Deviation 3 |
| Baclofen 10mg Three Times Daily | Reduced Severity of Alcohol Withdrawal as Measured by Severity of Ethanol Withdrawal Score. . | Highest SEWS score at 72 hours | 2 Unit on Scale | Standard Deviation 3 |
| Sugar Pill Given Three Times Daily | Reduced Severity of Alcohol Withdrawal as Measured by Severity of Ethanol Withdrawal Score. . | Highest SEWS score at 24 hours | 6 Unit on Scale | Standard Deviation 4 |
| Sugar Pill Given Three Times Daily | Reduced Severity of Alcohol Withdrawal as Measured by Severity of Ethanol Withdrawal Score. . | Highest SEWS score at 48 hours | 4 Unit on Scale | Standard Deviation 4 |
| Sugar Pill Given Three Times Daily | Reduced Severity of Alcohol Withdrawal as Measured by Severity of Ethanol Withdrawal Score. . | Highest SEWS score at 72 hours | 3 Unit on Scale | Standard Deviation 3 |