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

NCT ID: NCT02090504

Last Updated: 2014-03-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 127 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2002-02-28
• Study Completion Date: 2009-05-31

Brief Summary

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

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.

Conditions

Alcohol Withdrawal Syndrome; Alcohol Dependence

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Sodium oxybate (SMO)

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.

Group Type: EXPERIMENTAL

Sodium Oxybate (SMO)

Intervention Type: DRUG

Oxazepam

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).

Group Type: ACTIVE_COMPARATOR

Oxazepam

Intervention Type: DRUG

Interventions

Sodium Oxybate (SMO)

Intervention Type: DRUG

Oxazepam

Intervention Type: DRUG

Other Intervention Names

Gamma-hydroxy butyrate (GHB)

Eligibility Criteria

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.

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

CT Pharmaceutical Industries, Sanremo - Italy

UNKNOWN

Sponsor Role: collaborator

University of Bologna

OTHER

Sponsor Role: collaborator

Medical University of Vienna

OTHER

Sponsor Role: collaborator

Catholic University of the Sacred Heart

OTHER

Sponsor Role: lead

Responsible Party

Giovanni Addolorato

Professor of Internal Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Otto Lesch, MD, Prof.

Role: PRINCIPAL_INVESTIGATOR

Department of Psychiatry, University of Wien

Giovanni Addolorato, MD

Role: STUDY_DIRECTOR

Department of Internal Medicine, Catholic University of Rome

Locations

University of Wien

Vienna, AT, Austria

"G. Fontana" Centre for the Study and Multidisciplinary Treatment of Alcohol Addiction, Department of Clinical Medicine, University of Bologna

Bologna, BO, Italy

Catholic University of Rome

Rome, Rm, Italy

Countries

Austria; Italy

References

Skala K, Caputo F, Mirijello A, Vassallo G, Antonelli M, Ferrulli A, Walter H, Lesch O, Addolorato G. Sodium oxybate in the treatment of alcohol dependence: from the alcohol withdrawal syndrome to the alcohol relapse prevention. Expert Opin Pharmacother. 2014 Feb;15(2):245-57. doi: 10.1517/14656566.2014.863278. Epub 2013 Nov 28.

Reference Type: BACKGROUND

PMID: 24283802 (View on PubMed)

Caputo F, Skala K, Mirijello A, Ferrulli A, Walter H, Lesch O, Addolorato G. Sodium oxybate in the treatment of alcohol withdrawal syndrome: a randomized double-blind comparative study versus oxazepam. The GATE 1 trial. CNS Drugs. 2014 Aug;28(8):743-52. doi: 10.1007/s40263-014-0183-1.

Reference Type: DERIVED

PMID: 24996524 (View on PubMed)

Other Identifiers

GATE-I

Identifier Type: -

Identifier Source: org_study_id