Comparative Study of Gamma-hydroxy Butyrate Versus Oxazepam in the Treatment of Alcohol Withdrawal Syndrome (GATE I)

Catholic University of the Sacred Heart

Status and phase: Completed; Phase 4

Conditions: Alcohol Withdrawal Syndrome; Alcohol Dependence

Treatments: Drug: Oxazepam; Drug: Sodium Oxybate (SMO)

Study type: Interventional

Funder types: Other

Identifiers

NCT02090504

GATE-I

Details and patient eligibility

About

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).

Full description

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.

Enrollment: 127 patients

Sex: All

Ages: 21 to 75 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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127 participants in 2 patient groups

Sodium oxybate (SMO)

Experimental group

Description:

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.

Treatment:

Drug: Sodium Oxybate (SMO)

Oxazepam

Active Comparator group

Description:

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).

Treatment:

Drug: Oxazepam