A Randomized, Double-Blinded, Placebo-Controlled Study Evaluating Phenobarbital and Ketamine Adjunctive Therapies in the Treatment of Alcohol Withdrawal Syndrome
试验速览
- 阶段
- 4 期
- 状态
- 撤回
- 主要终点
- Intensive Care Unit admission rate
研究概览
简要总结
The goal of this study will aim to determine if adding phenobarbital or ketamine to a symptom-triggered benzodiazepine regimen decreases the rate of intensive care unit admissions during the treatment of alcohol withdrawal syndrome when compared to symptom-triggered benzodiazepine therapy alone.
详细描述
The primary objective of this study is to compare phenobarbital and ketamine adjunctive therapies to lorazepam-based therapy in the treatment of acute alcohol withdrawal syndrome.
It is hypothesized that the use of an alternative agent, either phenobarbital or ketamine, when used as an adjunct to symptom-triggered lorazepam therapy will significantly reduce the rate of intensive care unit admissions and thereby reduce the total cost associated with hospital admission for treatment of alcohol withdrawal syndrome.
Enrolled patients will be admitted to Santa Barbara Cottage Hospital where they will be monitored with continuous pulse oximetry and cardiac telemetry. They will remain hospitalized while undergoing study-guided therapy in addition to supportive care for acute alcohol withdrawal syndrome. Patients will undergo standard of care therapy with lorazepam symptom-triggered therapy regardless of study participation.
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
- Triple (Participant, Care Provider, Investigator)
盲法说明
Each participant will be randomized according to a web-based randomization program employed by a research pharmacist once the Emergency Department provider deems the patient appropriate for inpatient treatment of alcohol withdrawal syndrome.
Each medication will be packaged by Santa Barbara Cottage Hospital pharmacy. In order to blind both the clinicians and the participants, the pharmacy will provide medication bags that are identical. Therefore, Emergency Department nursing staff and physicians will be unaware of which study drug is being provided to the patient. Normal saline will be used as a placebo to mimic study drugs (phenobarbital and ketamine). Pharmacy will remain unblinded and maintain records of which treatment assignment is prepared for each patient.
Treatment will be provided for the duration of the patient's hospitalization; therefore, treatment compliance will be documented in the electronic health record using the medication bag identifier.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Primary admitting diagnosis of acute alcohol withdrawal syndrome based on International Statistical Classification of Diseases and Related Health Problems 10th Revision (ICD-10), code F10.3, F10.4.
排除标准
- •Significant comorbid medical illness requiring Intensive Care Unit admission;
- •Pregnancy;
- •Inability to obtain intravenous access;
- •Child Pugh Class C; and
- •Allergy to study medications (phenobarbital, ketamine, lorazepam).
研究组 & 干预措施
Lorazepam + Ketamine + Placebo A
Ketamine - infusion (0.15 - 0.4 mg/kg/hr) and placebo injections titrated by increases of 0.075 mg/kg/hr every 30 minutes for Clinical Institute Withdrawal Assessment for Alcohol (revised version) (CIWA-Ar) greater than or equal to 10 in addition to lorazepam symptom-triggered therapy
Ketamine dosing will be based on ideal body weight
Ketamine infusion will be discontinued once CIWA-Ar less than 10 for 4 hours
干预措施: Ketamine (Drug)
Lorazepam + Ketamine + Placebo A
Ketamine - infusion (0.15 - 0.4 mg/kg/hr) and placebo injections titrated by increases of 0.075 mg/kg/hr every 30 minutes for Clinical Institute Withdrawal Assessment for Alcohol (revised version) (CIWA-Ar) greater than or equal to 10 in addition to lorazepam symptom-triggered therapy
Ketamine dosing will be based on ideal body weight
Ketamine infusion will be discontinued once CIWA-Ar less than 10 for 4 hours
干预措施: Lorazepam (Drug)
Lorazepam + Ketamine + Placebo A
Ketamine - infusion (0.15 - 0.4 mg/kg/hr) and placebo injections titrated by increases of 0.075 mg/kg/hr every 30 minutes for Clinical Institute Withdrawal Assessment for Alcohol (revised version) (CIWA-Ar) greater than or equal to 10 in addition to lorazepam symptom-triggered therapy
Ketamine dosing will be based on ideal body weight
Ketamine infusion will be discontinued once CIWA-Ar less than 10 for 4 hours
干预措施: Placebo A (Drug)
Lorazepam + Phenobarbital + Placebo B
Phenobarbital - IV push (260 mg loading followed by 130 mg q1 hour) with placebo infusion until CIWA-Ar less than 10 with a maximum daily dose of 10mg/kg in addition to lorazepam symptom-triggered dosing for recurrent symptoms (Gold 2007)
Maximum daily dose will be used in order to prevent over sedation as well as provide adequate storage in pharmacy monitored refrigerators for study drugs
干预措施: Phenobarbital (Drug)
Lorazepam + Phenobarbital + Placebo B
Phenobarbital - IV push (260 mg loading followed by 130 mg q1 hour) with placebo infusion until CIWA-Ar less than 10 with a maximum daily dose of 10mg/kg in addition to lorazepam symptom-triggered dosing for recurrent symptoms (Gold 2007)
Maximum daily dose will be used in order to prevent over sedation as well as provide adequate storage in pharmacy monitored refrigerators for study drugs
干预措施: Lorazepam (Drug)
Lorazepam + Phenobarbital + Placebo B
Phenobarbital - IV push (260 mg loading followed by 130 mg q1 hour) with placebo infusion until CIWA-Ar less than 10 with a maximum daily dose of 10mg/kg in addition to lorazepam symptom-triggered dosing for recurrent symptoms (Gold 2007)
Maximum daily dose will be used in order to prevent over sedation as well as provide adequate storage in pharmacy monitored refrigerators for study drugs
干预措施: Placebo B (Drug)
Lorazepam + Placebo A + Placebo B
Lorazepam will be administered every 30 minutes as indicated based on CIWA-Ar protocol for Cottage Health in addition to placebo injections and placebo infusion
干预措施: Lorazepam (Drug)
Lorazepam + Placebo A + Placebo B
Lorazepam will be administered every 30 minutes as indicated based on CIWA-Ar protocol for Cottage Health in addition to placebo injections and placebo infusion
干预措施: Placebo A (Drug)
Lorazepam + Placebo A + Placebo B
Lorazepam will be administered every 30 minutes as indicated based on CIWA-Ar protocol for Cottage Health in addition to placebo injections and placebo infusion
干预措施: Placebo B (Drug)
结局指标
主要结局
Intensive Care Unit admission rate
时间窗: Presentation to Emergency Department through hospital stay, data will be utilized through study completion, anticipated 2 years
Number of admissions to the intensive care unit
次要结局
- Incidence of withdrawal seizures(Presentation to Emergency Department through hospital stay, data will be utilized through study completion, anticipated 2 years)
- Incidence of alcohol withdrawal hallucinations(Presentation to Emergency Department through hospital stay, data will be utilized through study completion, anticipated 2 years)
- Clinical Institute Withdrawal Assessment of Alcohol Scale, Revised (CIWA-Ar) scores(Presentation to Emergency Department through hospital stay, data will be utilized through study completion, anticipated 2 years)
- Cumulative dose of medication/s administered(Presentation to Emergency Department through hospital stay, data will be utilized through study completion, anticipated 2 years)
- Rate of mechanical ventilation(Presentation to Emergency Department through hospital stay, data will be utilized through study completion, anticipated 2 years)
- Incidence of refractory alcohol withdrawal requiring alternative sedation with dexmedetomidine, propofol or midazolam infusions(Presentation to Emergency Department through hospital stay, data will be utilized through study completion, anticipated 2 years)