The Gamma Hydroxybutyric Acid in Alcohol-dependence Treatment Efficacy (GATE) I Trial: a Comparative Study Versus Oxazepam in the Treatment of Alcohol Withdrawal Syndrome
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 127
- 试验地点
- 3
- 主要终点
- Efficacy of GHB compared to oxazepam on alcohol withdrawal symptoms
研究概览
简要总结
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).
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 21 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- 未提供
研究组 & 干预措施
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.
干预措施: Sodium Oxybate (SMO) (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).
干预措施: Oxazepam (Drug)
结局指标
主要结局
Efficacy of GHB compared to oxazepam on alcohol withdrawal symptoms
时间窗: day 1, day 10, day 20
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).
次要结局
- Course of alcohol abstinence(day 1, day 10, day 20)
研究者
Giovanni Addolorato
Professor of Internal Medicine
Catholic University, Italy