Multicenter Randomized Placebo Controlled Trial Assessing the Efficacy of Oral Adjuvant Magnesium Supplementation in the Treatment of Alcohol Withdrawal Syndrome
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 105
- 试验地点
- 11
- 主要终点
- Between-group absolute difference of the CIWA-Ar score (revised clinical institute withdrawal assessment for alcohol scale) change from baseline
研究概览
简要总结
This study examine the efficacy of oral magnesium supplementation as an adjuvant therapy for decreasing intensity of alcohol withdrawal symptoms among inpatients requiring pharmacological treatment of their AWS. This double blind randomized multicenter clinical trial planned to treat half of participants as usal plus placebo and the other half as usual plus magnesium.
详细描述
Alcohol withdrawal syndrome (AWS) is a frequent and potentially fatal outcome. It is crucial to treat AWS in order to reduce symptoms severity, to prevent severe complications and to increase patient motivation to maintain long-term alcohol abstinence. Clarify the relevance of oral magnesium supplementation as a routine adjuvant therapy of AWS can give rise to a major evolution of guidelines regarding management of alcohol use disorder and make AWS more comfortable for hundred thousand patients.
Magnesium acts as a competitor of glutamate on NMDA receptor binding site, limiting glutamate toxicity leading to AWS. Previous findings suggested a correlation between AWS intensity and hypomagnesaemia degree, and an increased risk of severe AWS (i.e. delirium tremens and seizure) when there is deep depletion. In addition to magnesium role as a glutamatergic modulator via an NMDA-receptor antagonism activity, magnesium may also modulate GABAergic neurotransmission and affect numerous transduction pathways, including proteinkinase C, possibly influencing the access of corticosteroids to the brain.
Moreover, magnesium has been found to be a cofactor required for thiamine-dependent enzymes whereas thiamine supplementation is crucial to prevent from Wernicke's encephalopathy in the treatment of AWS. Finally, magnesium supplementation could help to reduce benzodiazepines use.
The primary endpoint is the between-group absolute difference of the revised clinical institute withdrawal assessment for alcohol scale (CIWA-Ar) score change from baseline, 3 days after randomization.
The secondary endpoints are:
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
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult inpatients, men and women (i.e. age>18 years and <75 years) ;
- •Current AWS according to DSM-5 criteria;
- •Score at the revised clinical institute withdrawal assessment for alcohol scale (CIWA-Ar) >8;
- •Written informed consent to participate in the study;
- •Affiliation to the French Social Security Health Care plan.
排除标准
- •Age less than 18 or greater than 75;
- •Hemodynamic failure;
- •Arythmia;
- •Lack of fulfilling AWS criteria according to DSM-5;
- •Score at the revised clinical institute withdrawal assessment for alcohol scale (CIWA-Ar) <=8;
- •Benzodiazepine misuse according to the opinion of the investigator;
- •Substance use disorder according to the opinion of the investigator, regarding licit and illicit substances, except for tobacco;
- •Pregnancy or breast-feeding;
- •Unable to take oral medications;
- •Creatinine clearance < 45mL/min less than 6 months old. If there is no dosage in the last 6 months, creatinine clearance must be <30mL/min at inclusion (creatinine clearance computed according to the Cockcroft-Gault Equation);
- •Cognitive disorders already known at inclusion that impair the informed consent, including dementia (except for acute withdrawal delirium), according to the opinion of the investigator;
- •Psychiatric disorder requiring hospitalization or specific cares in emergency (e.g. suicidal crisis, acute psychotic episode);
- •Magnesium supplementation (regardless the type of delivery) within 3 months prior to inclusion;
- •Actual quinidine intake;
- •No written informed consent to participate in the study;
- •Patient under tutorship or curatorship;
- •Hypersensitivity to Magnespasmyl® or to any of its excipients (including sucrose) or to lactose (placebo excipient).
研究组 & 干预措施
Intervention
Usual care (i.e. without any restriction of drug therapy) plus oral tablet magnesium supplementation: 426.6mg of magnesium per day three times daily (i.e. 142.2 mg for each shot) throughout the study (i.e. fifteen days). In case of diarrhea, nearly half-dosage will be used (i.e. 189.6mg).
干预措施: Magnesium (Drug)
Control
Usual care (i.e. without any restriction of drug therapy) plus oral placebo, totally similar to the verum, three times daily throughout the study (i.e. fifteen days). In case of diarrhea, nearly half-dosage will be used.
干预措施: Placebo Oral Tablet (Drug)
结局指标
主要结局
Between-group absolute difference of the CIWA-Ar score (revised clinical institute withdrawal assessment for alcohol scale) change from baseline
时间窗: 3 days after randomization
次要结局
- Total benzodiazepine consumption compared between experimental and control groups throughout the duration of the study(15 days after randomization)
- The delay compared between experimental and control groups until having a total score of 0 at the CIWA-Ar(15 days after randomization)
- The rate of patients experiencing seizures and delirium tremens during the study compared between intervention and control groups(15 days after randomization)
- Between-group absolute difference of the CIWA-Ar score change from baseline, considering two subgroups: score at the Charlson Comorbidity Index (CCI) min-score at the CCI median versus score score at the CCI median-score at the CCI min(3 days after randomization)
- Between-group absolute difference of the CIWA-Ar score (revised clinical institute withdrawal assessment for alcohol scale) change from baseline considering two subgroups: 18-59 years versus 60-75 years(3 days after randomization)
- The number of participants who left the hospital against medical advice during the study compared between intervention and control groups(15 days after randomization)
- The number of participants who made an appointment in an addiction unit during the study compared between intervention and control groups after stratification following alcohol use disorder (AUD) duration and number of previous addiction healthcare(15 days after randomization)
- Patient Satisfaction Questionnaire-18 scores at the last follow-up point compared between experimental and control groups(15 days after randomization)
- Total plasmatic or serum magnesium concentration changes between baseline,3 days after baseline, and 7 days after baseline, compared between intervention and control groups(3 days and 7 days after randomization)
- Rate of all adverse events occurred during the study and compare their incidence between intervention and control groups(15 days after randomization)