A Double-blind, Placebo-controlled, Randomized Clinical Trial of Allopregnanolone for the Treatment of Traumatic Brain Injury
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 13
- 试验地点
- 1
- 主要终点
- Extended Glasgow Outcome Scale (GOS-E) Score
研究概览
简要总结
This study will provide initial data on the safety and effectiveness of allopregnanolone in improving neurobehavioral outcome and reducing mortality in adults with moderate and severe traumatic brain injury.
详细描述
This is a double-blind, placebo-controlled, randomized, dose-finding, two-stage adaptive, clinical trial study comparing allopregnanolone to placebo when administered intravenously for 5 days beginning within 8 hours after injury. Test products to be administered are low and high dose allopregnanolone (Products L and H, respectively) and placebo (Product P) intravenous solutions. The products are administered during a 4-day treatment period followed by a 1-day dose de-escalation period. Stage 1 of the study will assess safety and confirm that dosing with Products L and H achieve the target steady-state plasma concentrations set for each of these products. Dosing will be adjusted in Stage 1, if necessary. Stage 2 will initially allocate subjects equally to Products L, H and P but will then use adaptive randomization to allocate subjects between Products L and H to optimized the probability of yielding a better 3-month Glasgow Outcome Score Extended (GOS-E) score.
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
- 16 Years 至 65 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •English or Spanish speaking person
- •Moderate to severe closed or blunt traumatic brain injury [post resuscitation Glasgow Coma Score (GCS) 3-12 with abnormal head CT scan if GCS is 9-12]
- •Less than 8 hours from injury to study initiation
- •Able to participate for the full term of the study
排除标准
- •Subjects with life expectancy of less than 24 hours
- •Isolated epidural hematoma
- •Hypoxia (pulse oximetry saturation ≤90% for 15 or more minutes before enrollment)
- •Hypotension (systolic blood pressure ≤90 mm Hg on 2 or more reliable measurements before enrollment)
- •Cardiopulmonary arrest prior to randomization
- •Spinal cord injury with motor deficits
- •Bilateral non-reactive pupils with Glasgow Coma Scale 3
- •Body weight >120 kg
- •Pregnancy
- •Active breast or reproductive organ cancer
- •Allergy to progesterone
- •History of thromboembolic events
- •Receipt of activated Factor VII before enrollment
- •Any disease that is unstable or which could jeopardize the safety of the subject including severe renal impairment (creatinine clearance <50 ml/min)
- •Prisoner/ward of the state
- •Known treatment with another investigational drug therapy or procedure within 30 days of injury
研究组 & 干预措施
Allopregnanolone
Allopregnanolone injection (intravenous solution) continuous infusion for 5 days
干预措施: Allopregnanolone injection (Drug)
Placebo
Placebo injection (intravenous solution) continuous infusion for 5 days
干预措施: Placebo injection (Drug)
结局指标
主要结局
Extended Glasgow Outcome Scale (GOS-E) Score
时间窗: 6 months after injury
GOS-E is a global scale for functional outcome that rates patient status into one of 8 levels. The minimum score is 1 and the maximum score is 8. 1 = dead; 2 = vegetative state; 3 = low severe disability; 4 = upper severe disability; 5 = low moderate disability; 6 = upper moderate disability; 7 = low good recovery; 8 = upper good recovery. GOS-E was assessed by 19 question structured interview.
次要结局
未报告次要终点
研究者
Michael A. Rogawski, MD, PhD
Principal Invstigator
University of California, Davis