Gabapentin vs Chlordiazepoxide for Ambulatory Alcohol Withdrawal
Study Details
Study Description
Brief Summary
A randomized, double-blind controlled trial comparing treatment outcomes between chlordiazepoxide, or gabapentin to treat alcohol withdrawal syndrome in alcohol dependent veteran subjects. The objective of this trial is to compare the safety and effectiveness of these two medications. Intervention is a fixed dose taper of chlordiazepoxide, or gabapentin over 6 days. Subjects will be evaluated for 7-10 days to monitor alcohol abstinence, withdrawal severity scores, adverse events including ataxia, sedation, cognitive function and alcohol craving.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 4 |
Detailed Description
Chlordiazepoxide 25 mg and matching placebo capsules or gabapentin 300 mg and matching placebo capsules were were used. The chlordiazepoxide/placebo and gabapentin/placebo capsules were not identical in appearance. Study medications were packaged into a 7-day medication organizer. The dosing for each subject was either gabapentin 1200mg or chlordiazepoxide 100 mg orally days 1-3, gabapentin 900 mg or chlordiazepoxide 75 mg day 4, gabapentin 600 mg or chlordiazepoxide 50 mg day 5, and gabapentin 300 mg or chlordiazepoxide 25 mg day 6.
Adherence was assessed by pill counts and serum samples were obtained for study drug analysis. Serum samples were batched and sent to a contract laboratory so that study clinicians were blinded to the results until after the trial was completed. Presence of the assigned study medication in the blood served as a surrogate adherence marker.
Subjects also received prescriptions for daily oral therapeutic multiple vitamin tablets, folic acid 1 mg, and thiamine 100 mg.
A psychiatric history and physical examination, breath alcohol concentration, vital signs, CIWA-Ar (alcohol withdrawal scale), and blood chemistry including transaminases and complete blood cell count were obtained for baseline for all participants. Subjects were seen on weekdays for clinic follow-up appointments. Assessments performed at each study visit included CIWA-Ar, ESS (Epworth Sleepiness Scale), PACS (Penn Alcohol Craving Scale), and a brief examination to document mental status and assess coordination, which included assessment of stance, tandem gait, Romberg test, pronator drift, toe and heel walk, rapid-alternating-movements, and point-to-point movements. Breath alcohol concentration (BAC) was also measured (AlcoSensor, Intoximeters, Inc.) at each visit.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Chlordiazepoxide Chlordiazepoxide 25mg capsule or matching placebo capsule |
Drug: Chlordiazepoxide
25mg four times daily x 3 days then tapered over 3 days
Other Names:
|
| Experimental: Gabapentin Gabapentin 300mg capsule or matching placebo capsule |
Drug: Gabapentin
300mg four times daily x 3 days then tapered over 3 days
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Epworth Sleepiness Scale (ESS) [1 week]
ESS is an 8 item-scale and scores range between 0 and 24. The higher the score implies more daytime sleepiness.
- PENN Alcohol Craving Scale [1 week]
PENN is a 5 item self-rated scale of alcohol craving. Scores range from 0 (little craving for alcohol) to 30 (irresistable urge to drink alcohol)
Secondary Outcome Measures
- Clinical Institute Withdrawal Assessment-Alcohol (Revised)(CIWA-Ar) [1 week]
CIWA-Ar measures severity of 10 observed or measured alcohol withdrawal signs or symptoms. Total score ranges from 0 (best possible outcome)-67 (worst possible outcome). Many previously publications suggest a total score of 8-10 is severe enough to warrant medication treatment. Lower scores (0-8) represent fewer withdrawal symptoms and less severity, scores > 8 represent more withdrawal symptoms and greater severity
Eligibility Criteria
Criteria
Inclusion Criteria:
- Alcohol dependent at risk for withdrawal symptoms
Exclusion Criteria:
- Benzodiazepine dependent
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | George E Wahlen VA Medical Center | Salt Lake City | Utah | United States | 84148 |
Sponsors and Collaborators
- VA Salt Lake City Health Care System
Investigators
- Principal Investigator: Christopher J Stock, PharmD, Salt Lake VA Health Care System
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- UU40574
Study Results
Participant Flow
| Recruitment Details | Subjects recruited from VA outpatient detoxification clinic |
|---|---|
| Pre-assignment Detail | Exclusions: subjects requiring hospitalization, receiving benzodiazepines prior to randomization and subjects not likely to follow instructions. |
| Arm/Group Title | Chlordiazepoxide | Gabapentin |
|---|---|---|
| Arm/Group Description | 25mg four times daily x 3 days, 25mg three times daily x 1 day, 25mg twice daily x 1 day, 25mg at bedtime x 1 day then discontinue | 300mg four times daily x 3 days, 300mg three times daily x 1 day, 300mg twice daily x 1 day, 300mg at bedtime x 1 day then discontinue |
| Period Title: Overall Study | ||
| STARTED | 9 | 17 |
| COMPLETED | 6 | 11 |
| NOT COMPLETED | 3 | 6 |
Baseline Characteristics
| Arm/Group Title | Chlordiazepoxide | Gabapentin | Total |
|---|---|---|---|
| Arm/Group Description | 25mg qid x 3 days, 25mg tid x 1 day, 25mg bid x 1 day, 25mg hs x 1 day then d/c | 300mg qid x 3 days, 300mg tid x 1 day, 300mg bid x 1 day, 300mg hs x 1 day then d/c | Total of all reporting groups |
| Overall Participants | 9 | 17 | 26 |
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
55.8
(4.8)
|
51.1
(7.7)
|
52.7
(6.6)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
1
11.1%
|
0
0%
|
1
3.8%
|
| Male |
8
88.9%
|
17
100%
|
25
96.2%
|
Outcome Measures
| Title | Epworth Sleepiness Scale (ESS) |
|---|---|
| Description | ESS is an 8 item-scale and scores range between 0 and 24. The higher the score implies more daytime sleepiness. |
| Time Frame | 1 week |
Outcome Measure Data
| Analysis Population Description |
|---|
| Late withdrawal period days 5-7 |
| Arm/Group Title | Chlordiazepoxide | Gabapentin |
|---|---|---|
| Arm/Group Description | 25mg four times daily x 3 days, 25mg three times daily x 1 day, 25mg twice daily x 1 day, 25mg at bedtime x 1 day then discontinue | 300mg four times daily x 3 days, 300mg three times daily x 1 day, 300mg twice daily x 1 day, 300mg at bedtime x 1 day then discontinue |
| Measure Participants | 9 | 17 |
| Mean (95% Confidence Interval) [units on a scale] |
6.35
|
2.65
|
| Title | PENN Alcohol Craving Scale |
|---|---|
| Description | PENN is a 5 item self-rated scale of alcohol craving. Scores range from 0 (little craving for alcohol) to 30 (irresistable urge to drink alcohol) |
| Time Frame | 1 week |
Outcome Measure Data
| Analysis Population Description |
|---|
| Late withdrawal period days 5-7 |
| Arm/Group Title | Chlordiazepoxide | Gabapentin |
|---|---|---|
| Arm/Group Description | 25mg four times daily x 3 days, 25mg three times daily x 1 day, 25mg twice daily x 1 day, 25mg at bedtime x 1 day then discontinue | 300mg four times daily x 3 days, 300mg three times daily x 1 day, 300mg twice daily x 1 day, 300mg at bedtime x 1 day then discontinue |
| Measure Participants | 9 | 17 |
| Mean (95% Confidence Interval) [units on a scale] |
16.78
|
10.74
|
| Title | Clinical Institute Withdrawal Assessment-Alcohol (Revised)(CIWA-Ar) |
|---|---|
| Description | CIWA-Ar measures severity of 10 observed or measured alcohol withdrawal signs or symptoms. Total score ranges from 0 (best possible outcome)-67 (worst possible outcome). Many previously publications suggest a total score of 8-10 is severe enough to warrant medication treatment. Lower scores (0-8) represent fewer withdrawal symptoms and less severity, scores > 8 represent more withdrawal symptoms and greater severity |
| Time Frame | 1 week |
Outcome Measure Data
| Analysis Population Description |
|---|
| Late withdrawal period days 5-7 |
| Arm/Group Title | Chlordiazepoxide | Gabapentin |
|---|---|---|
| Arm/Group Description | 25mg four times daily x 3 days, 25mg three times daily x 1 day, 25mg twice daily x 1 day, 25mg at bedtime x 1 day then discontinue | 300mg four times a day x 3 days, 300mg three times daily x 1 day, 300mg twice daily x 1 day, 300mg at bedtime x 1 day then discontinue |
| Measure Participants | 9 | 17 |
| Mean (95% Confidence Interval) [units on a scale] |
3.29
|
4.33
|
Adverse Events
| Time Frame | 7 days | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | Daily assessments of mental status, stance, tandem gait, Romberg test, pronator drift, toe and heel walk, rapid-alternating-movements, and point-to-point movements. | |||
| Arm/Group Title | Chlordiazepoxide | Gabapentin | ||
| Arm/Group Description | 25mg qid x 3 days, 25mg tid x 1 day, 25mg bid x 1 day, 25mg hs x 1 day then d/c | 300mg qid x 3 days, 300mg tid x 1 day, 300mg bid x 1 day, 300mg hs x 1 day then d/c | ||
All Cause Mortality |
||||
| Chlordiazepoxide | Gabapentin | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Chlordiazepoxide | Gabapentin | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/9 (0%) | 0/17 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Chlordiazepoxide | Gabapentin | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/9 (0%) | 0/17 (0%) | ||
Limitations/Caveats
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.
Results Point of Contact
| Name/Title | Dr. Christopher Stock |
|---|---|
| Organization | VA Salt Lake City Medical Center |
| Phone | 801-582-1565 ext 1172 |
| christopher.stock@va.gov |
- UU40574