Alcoholism, Alcohol Withdrawal
Conditions
Brief summary
The purpose of this study is determine if the medication baclofen can prevent the symptoms of Alcohol Withdrawal Syndrome (AWS) in hospitalized patients who may be at risk for AWS. This medication is most often used for patients who have spasticity of their muscles due to a neuromuscular disease. In several European studies, and in an earlier study at Essentia Health (NCT00597701), baclofen has been found to have a significant effect on the severity of symptoms of AWS.
Interventions
DRUGBaclofen
Baclofen 10 mg every 8 hours for 72 hours (9 doses) as an inpatient, or until discharge if before 72 hours.
DRUGPlacebo
Identical appearing placebo every 8 hours for 72 hours (9 doses) as an inpatient, or until discharge if before 72 hours.
Sponsors
Essentia Health
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
21 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adults (\>21) admitted to inpatients units of 1 of 3 Essentia Health hospitals * Patient placed on AWS watch protocol by admitting physicians.
Exclusion criteria
* Unable to provide informed consent * Unable to take swallow oral medications (tube-fed patients are to be excluded) * Admitted for AWS or with Clinical Institute Withdrawal Assessment of Alcohol Scale, Revised (CIWA-Ar) score \>8 at baseline * No alcohol intake for ≥ 48 hours or AUDIT score \<12 at baseline * 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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Moderate or Severe Alcohol Withdrawal Syndrome | 72 hours | Moderate or severe AWS was defined as a CIWA-AR score of at least 11. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Severity of Alcohol Withdrawal Symptoms as Measured on the CIWA-Ar Scale and Assessed at 24, 48, and 72 Hours After Enrollment | 72 hours | Range: 0 to 67; larger values indicate greater severity |
| Peak and Total Benzodiazepine Dose Required | 72 hours | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo every eight hours as inpatients for 72 hours or until discharge if less than 72 hours | 9 |
| Baclofen Baclofen 10 mg every 8 hours for 72 hours (9 doses) as an inpatient, or until discharge if before 72 hours | 8 |
| Total | 17 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 1 |
Baseline characteristics
| Characteristic | Placebo | Baclofen | Total |
|---|---|---|---|
| Age, Continuous | 53.9 years STANDARD_DEVIATION 11.37 | 48.9 years STANDARD_DEVIATION 11.97 | 51.5 years STANDARD_DEVIATION 11.58 |
| Baseline Clinical Institute Withdrawal Assessment of Alcohol Scale, Revised (CIWA-Ar) | 4.4 units on a scale STANDARD_DEVIATION 2.01 | 3.9 units on a scale STANDARD_DEVIATION 2.42 | 4.2 units on a scale STANDARD_DEVIATION 2.16 |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 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 | 6 Participants | 8 Participants | 14 Participants |
| Region of Enrollment United States | 9 participants | 8 participants | 17 participants |
| Sex: Female, Male Female | 2 Participants | 1 Participants | 3 Participants |
| Sex: Female, Male Male | 7 Participants | 7 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 9 | 0 / 8 |
| serious Total, serious adverse events | 0 / 9 | 0 / 8 |
Outcome results
Primary
Moderate or Severe Alcohol Withdrawal Syndrome
Moderate or severe AWS was defined as a CIWA-AR score of at least 11.
Time frame: 72 hours
Population: Subjects who either had AWS prior to the collection of the 72-hour CIWA-Ar score or had a CIWA-Ar score either recorded as the 72-hour CIWA-Ar score or occurring within the one-hour window for the 72-hour CIWA-Ar score are evaluable for this endpoint.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Moderate or Severe Alcohol Withdrawal Syndrome | 2 Participants |
| Baclofen | Moderate or Severe Alcohol Withdrawal Syndrome | 0 Participants |
p-value: 0.033490% CI: [-0.7275, -0.0206]z-statistic with pooled estimate
Secondary
Peak and Total Benzodiazepine Dose Required
Time frame: 72 hours
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Peak and Total Benzodiazepine Dose Required | Peak Ativan 1mg PO equivalent dose | 1.0 Doses |
| Placebo | Peak and Total Benzodiazepine Dose Required | Total Ativan 1mg PO equivalent dose | 1.0 Doses |
| Baclofen | Peak and Total Benzodiazepine Dose Required | Peak Ativan 1mg PO equivalent dose | 0.5 Doses |
| Baclofen | Peak and Total Benzodiazepine Dose Required | Total Ativan 1mg PO equivalent dose | 0.5 Doses |
p-value: 0.33Wilcoxon (Mann-Whitney)
Comparison: Baclofen - Placebo; Total Ativan 1mg PO equivalent dosep-value: 0.8Wilcoxon (Mann-Whitney)
Secondary
Severity of Alcohol Withdrawal Symptoms as Measured on the CIWA-Ar Scale and Assessed at 24, 48, and 72 Hours After Enrollment
Range: 0 to 67; larger values indicate greater severity
Time frame: 72 hours
Population: All CIWA-Ar scores collected at and after the baseline measurement.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Severity of Alcohol Withdrawal Symptoms as Measured on the CIWA-Ar Scale and Assessed at 24, 48, and 72 Hours After Enrollment | 24 hours | 3.1325 units on a scale | Standard Error 0.5283 |
| Placebo | Severity of Alcohol Withdrawal Symptoms as Measured on the CIWA-Ar Scale and Assessed at 24, 48, and 72 Hours After Enrollment | 48 hours | 1.7913 units on a scale | Standard Error 0.4666 |
| Placebo | Severity of Alcohol Withdrawal Symptoms as Measured on the CIWA-Ar Scale and Assessed at 24, 48, and 72 Hours After Enrollment | 72 hours | 0.4501 units on a scale | Standard Error 0.5646 |
| Baclofen | Severity of Alcohol Withdrawal Symptoms as Measured on the CIWA-Ar Scale and Assessed at 24, 48, and 72 Hours After Enrollment | 24 hours | 2.4418 units on a scale | Standard Error 0.5572 |
| Baclofen | Severity of Alcohol Withdrawal Symptoms as Measured on the CIWA-Ar Scale and Assessed at 24, 48, and 72 Hours After Enrollment | 48 hours | 1.9878 units on a scale | Standard Error 0.443 |
| Baclofen | Severity of Alcohol Withdrawal Symptoms as Measured on the CIWA-Ar Scale and Assessed at 24, 48, and 72 Hours After Enrollment | 72 hours | 1.5339 units on a scale | Standard Error 0.4179 |
Comparison: Baclofen - Placebo; 24 hoursp-value: 0.3744Mixed Models Analysis
Comparison: Baclofen - Placebo; 48 hoursp-value: 0.7616Mixed Models Analysis
Comparison: Baclofen - Placebo; 72 hoursp-value: 0.1393Mixed Models Analysis