Comparative Study of Gamma-hydroxy Butyrate Versus Oxazepam in the Treatment of Alcohol Withdrawal Syndrome

Study Overview
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Brief Summary
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Benzodiazepines (BDZs) are the gold standard in the treatment of alcohol withdrawal syndrome (AWS). Gamma-Hydroxybutyric acid also known as sodium oxybate (SMO) has been tested as a treatment for AWS with encouraging results. Aim of this phase IV, multicenter randomized double-blind, double dummy study is to evaluate the efficacy of SMO in comparison to oxazepam in the treatment of alcohol withdrawal symptoms (AWS).

Detailed Description
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This is a phase IV, multicenter randomized (1:1), active drug-controlled study (double-blind, double dummy) with parallel groups evaluating the efficacy of SMO versus oxazepam in the treatment of AWS in alcohol-dependent patients. A placebo-controlled design was considered but excluded, given that a gold standard treatment for AWS is available (i.e., BDZs). Furthermore, considering that SMO and oxazepam have two different pharmaceutical formulation (suspension and tablets, respectively), a double-dummy design was adopted. Thus, all subjects will receive both medications, tablets (oxazepam or placebo) and suspension (SMO or placebo), at the same time.

Official Title
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The Gamma Hydroxybutyric Acid in Alcohol-dependence Treatment Efficacy (GATE) I Trial: a Comparative Study Versus Oxazepam in the Treatment of Alcohol Withdrawal Syndrome

Conditions
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Alcohol Withdrawal Syndrome, Alcohol Dependence

Intervention / Treatment
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* Drug: Sodium Oxybate (SMO)
* Drug: Oxazepam


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age range 21-75, diagnosis of alcohol dependence according to DSM-IV criteria the presence of AWS as assessed by Clinical Institute Withdrawal Assessment for Alcohol-revised (CIWA-Ar) scale, a scoring system for quantitative evaluation of physical symptoms of AWS.20 Only subjects with a CIWA-Ar score equal to or higher than 10 (defined as moderate or severe AWS requiring pharmacological treatment) were ultimately enrolled in the study. Exclusion criteria: ≤55 kg of body weight; history of withdrawal fits within 24 hours pre-study; history of epilepsy or epileptics seizures not properly controlled by established anti-epileptic treatment; dependence from narcotics, BDZs or other drugs of abuse; documented pre-existent hypersensitivity to SMO or to BDZs, renal failure (blood creatinine >2•5 mg/dl and/or documented proteinuria >500 mg/die), heart failure, severe respiratory failure hepatic encephalopathy stage II-IV; psychiatric disorders requiring treatment with psychoactive medications before the start of the study; treatment with clonidine, haloperidol, bromocriptine during the last 3 months prior to participation in the study; participation to other clinical investigations in the previous month prior to recruitment; females whose could not assure not to become pregnant during the 1 month period of treatment, and during the subsequent 3 weeks; subjects without a stable social condition or homeless.

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sodium oxybate (SMO)<br>Patients randomized to the first arm of the study will receive: SMO (sodium oxybate 175 mg/ml suspension): 10ml at 8.00 a.m., 10ml at 12.00 p.m., 10ml at 7.00 p.m. from day 1 to day 5, 5ml at 8.00 a.m., 5ml at 12.00 p.m., 5ml at 7.00 pm, on days 6 and 7, and 2.5ml at 8.00 a.m., 2.5 ml at 12.00 p.m., 2.5ml at 7.00 p.m. from day 8 to day 10 (If patient's weight is > 75 kg the dosage will be of 12ml instead of 10 ml, 6ml instead of 5ml, 3 ml instead of 2.5ml); placebo (tablets): 1 tablet at 8.00 a.m., 1 tablet at 12.00 p.m., 1 tablet at 7.00 p.m. from day 1 to day 10. | Drug: Sodium Oxybate (SMO)<br> <br> * Other names: Gamma-hydroxy butyrate (GHB);|
| Active Comparator: Oxazepam<br>Patients randomized to the second arm of the study will receive: OXAZEPAM (tablets): 60mg at 8.00 a.m., 60mg at 12.00 p.m., 90mg at 7.00 p.m. from day 1 to day 5, 30mg at 8.00 a.m., 30mg at 12.00 p.m., 30mg at 7.00 pm, on days 6 and 7, and 15mg at 8.00 a.m., 15mg at 12.00 p.m., 15mg at 7.00 p.m. from day 8 to day 10; placebo (suspension): 10ml at 8.00 a.m., 10ml at 12.00 p.m., 10ml at 7.00 p.m. from day 1 to day 5, 5ml at 8.00 a.m., 5ml at 12.00 p.m., 5ml at 7.00 pm, on days 6 and 7, and 2.5ml at 8.00 a.m., 2.5 ml at 12.00 p.m., 2.5ml at 7.00 p.m. from day 8 to day 10, (If patient's weight is > 75 kg the dosage will be of 12ml instead of 10 ml, 6ml instead of 5ml, 3 ml instead of 2.5ml). | Drug: Oxazepam<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy of GHB compared to oxazepam on alcohol withdrawal symptoms | The primary outcome was the reduction of symptoms of AWS reflected by the course of the total CIWA-Ar scores from the start (baseline) to the end of the study (day 10) and to the end of follow up (day 20, 10 days after drugs discontinuation). | day 1, day 10, day 20 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Course of alcohol abstinence | Secondary outcome variables included the course of alcohol abstinence. In order to confirm daily alcohol abstinence, a breath analyzer was used. In addition, to define those subjects remaining abstinent throughout the whole treatment period, carbohydrate-deficient transferrin (%CDT) was evaluated at the time of screening and at the end of the treatment period. | day 1, day 10, day 20 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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alcohol withdrawal syndrome, treatment, sodium oxybate, oxazepam