Alcohol Withdrawal Delirium
Conditions
Keywords
Alcohol withdrawal, Delirium tremors
Brief summary
The purpose of this study is determine if subjects with alcohol withdrawal who receive oral baclofen, plus standard benzodiazepine therapy, will experience less severe withdrawal symptoms than those who receive placebo plus standard benzodiazepine therapy.Subjects with alcohol withdrawal syndrome(AWS)who receive baclofen plus standard benzodiazepine therapy will experience fewer complications of AWS (as measured by use of additional sedatives, restraints, and/or intensive care unit \[ICU\] admissions) compared with subjects who receive placebo plus standard benzodiazepine therapy.
Detailed description
Alcohol use is ubiquitous in American society. 83% of Americans have ever consumed alcohol, 51% have in the lst month. The average American consumes 2.18 gallons of ethanol yearly. Alcohol related morbidity and mortality are staggering problems in the USA. Symptoms of alcohol withdrawal occur because alcohol is a central nervous system depressant; abrupt withdrawal unmasks compensatory overactivity of certain parts of the nervous system, including sympathetic autonomic outflow. 5% of patients who undergo alcohol suffer from Delirium Tremors (DTs), a syndrome characterized by hallucinations, disorientation, tachycardia, hypertension, low grade fever, agitation, and diaphoresis. DTs typically begin between 48-96 hours after the last drink and last 1 to 5 days. DTs requires hospitalization and vigorous activity in an ICU setting. The most successful drug treatment for alcohol withdrawal has been found to be the benzodiazepines. Symptom triggered treatment was found to be as effective as a fixed dose treatment to result in less drug being used overall, with a trend toward shorter duration of withdrawal treatment. Baclofen is used orally for the treatment of spasticity resulting from multiple sclerosis, spinal cord injuries/diseases and intrathecally for spasticity related to cerebral palsy, spinal cord injury, and amyotrophic lateral sclerosis (ALS). Its proposed benefit in alcohol withdrawal is that it may reduce voluntary alcohol intake, alcohol craving, and may suppress the intensity of alcohol withdrawal treatment.
Interventions
DRUGBaclofen
Baclofen 10 mg by mouth every 8 hours for 72 hours or until discharge if before 72 hours.
DRUGPlacebo
Placebo
DRUGLorazepam
Lorazepam was provided to all subjects (both arms of the study), as indicated by clinical condition. Standard symptom-triggered dosing of lorazepam for alcohol withdrawal was used. That is, the size and the frequency of the dose of lorazepam was determined by the severity of the alcohol withdrawal symptoms.
Sponsors
Essentia Health
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Meet Diagnostic and Statistical Manual, 4th version, revised (DSMr-IV) criteria for alcohol withdrawal syndrome (AWS). * Be an inpatient at St. Mary's Medical Center (SMMC) or Miller Dwan Medical Center (MDMC) at time of study enrollment. * Have an alcohol withdrawal score as measured by standard SMMC or MDMC inpatient protocol sufficient to trigger the use of benzodiazepine withdrawal therapy. * Agree to abstain for alcohol for duration of study. * Be able to provide informed consent.
Exclusion criteria
* The patient must not have any other active drug dependence in addition to alcohol. * Be unwilling or unable to forgo alcohol for the duration of the study. * Be using baclofen at the time of study enrollment. * Be using benzodiazepines for any reason other than acute alcohol withdrawal syndrome at time of study enrollment. * have known baclofen or benzodiazepine sensitivity. * Be unable to take oral (PO) meds. * Be unable to complete one of two consenting procedures. * Be pregnant or breastfeeding. * Have a serum creatine level \> 2.0. * Have a history of non alcoholic withdrawal seizures.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Benzodiazepine Doses Used to Treat Acutely-withdrawing Alcoholic Patients in the Baclofen-treated and Placebo-treated Groups | From eligibility for randomization (Clinical Institute Withdrawal Assessment [CIWA] score of at least 11) until 72 hours of observation had been completed. | In acutely-withdrawing alcoholic patients treated with either baclofen or placebo, symptom-driven benzodiazepine doses were assessed for the 72 hours following the first Clinical Institute Withdrawal Assessment (CIWA) score of 11 or greater. |
Countries
United States
Participant flow
Recruitment details
Seventy-nine subjects met study inclusion criteria, and provided informed consent for participation in the study.
Pre-assignment details
Of 79 enrolled subjects, 44 developed signs of Alcohol Withdrawal Syndrome (AWS) sufficient to meet Diagnostic and Statistical Manual, 4th version, revised (DSMr-IV) criteria for AWS. These 44 were randomized to receive baclofen or placebo, in addition to benzodiazepine therapy. Of the 44 subjects randomized, 31 completed 72 hours of observation.
Participants by arm
| Arm | Count |
|---|---|
| Baclofen Standard benzodiazepine therapy plus baclofen 10 mg every 8 hours for 72 hours (9 doses) as an inpatient, or until discharge if before 72 hours. | 25 |
| Placebo Standard benzodiazepine therapy plus placebo every eight hous as inpatients for 72 hours or until discharge if less than 72 hours. | 19 |
| Total | 44 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 0 | 1 |
| Overall Study | Did not start intervention (pharmacy er) | 0 | 2 |
| Overall Study | Physician Decision | 2 | 0 |
| Overall Study | Withdrawal by Subject | 5 | 5 |
Baseline characteristics
| Characteristic | Placebo | Baclofen | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 1 Participants | 2 Participants |
| Age, Categorical Between 18 and 65 years | 18 Participants | 24 Participants | 42 Participants |
| Age Continuous | 46.1 years STANDARD_DEVIATION 11.9 | 47.5 years STANDARD_DEVIATION 10.3 | 46.9 years STANDARD_DEVIATION 10.9 |
| Region of Enrollment United States | 19 participants | 25 participants | 44 participants |
| Sex: Female, Male Female | 1 Participants | 6 Participants | 7 Participants |
| Sex: Female, Male Male | 18 Participants | 19 Participants | 37 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 25 | 0 / 19 |
| serious Total, serious adverse events | 2 / 25 | 1 / 19 |
Outcome results
Primary
Benzodiazepine Doses Used to Treat Acutely-withdrawing Alcoholic Patients in the Baclofen-treated and Placebo-treated Groups
In acutely-withdrawing alcoholic patients treated with either baclofen or placebo, symptom-driven benzodiazepine doses were assessed for the 72 hours following the first Clinical Institute Withdrawal Assessment (CIWA) score of 11 or greater.
Time frame: From eligibility for randomization (Clinical Institute Withdrawal Assessment [CIWA] score of at least 11) until 72 hours of observation had been completed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Baclofen | Benzodiazepine Doses Used to Treat Acutely-withdrawing Alcoholic Patients in the Baclofen-treated and Placebo-treated Groups | 14.1 mg of benzodiazepine per 8 hours | Standard Deviation 8.9 |
| Placebo | Benzodiazepine Doses Used to Treat Acutely-withdrawing Alcoholic Patients in the Baclofen-treated and Placebo-treated Groups | 124.4 mg of benzodiazepine per 8 hours | Standard Deviation 290.3 |