A Phase II Trial on the Safety and Efficacy of C1 Inhibitor for the Acute Management of Severe Traumatic Brain Injury
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 106
- 试验地点
- 3
- 主要终点
- Therapy Intensity Level (TIL) Scale
研究概览
简要总结
Severe Traumatic Brain Injury (s-TBI) is a major cause of death and disability across all ages. Besides the primary impact, the pathophysiologic process of major secondary brain damage consists of a neuroinflammation response that critically leads to irreversible brain damage in the first days after the trauma. A key catalyst in this inflammatory process is the complement system. Inhibiting the complement system is therefore considered to be a potentially important new treatment for TBI, as has been shown in animal studies. This trial aims to study the safety and efficacy of C1-inhibitor compared to placebo in TBI patients. By temporarily blocking the complement system we hypothesize limitation of secondary brain injury and more favourable clinical outcome for TBI patients due to a decrease in the posttraumatic neuroinflammatory response.
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 64 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age at admission ≥ 18 years and < 65 years;
- •Clinical diagnosis of traumatic brain injury with GCS < 13 (with intracranial deviations);
- •Catheter placement for monitoring and management of increased ICP for at least 24 hours;
排除标准
- •A clear, non-traumatic cause of low GCS (e.g. toxic, cardial) on admission;
- •Not expected to survive more than 24 hours after admission;
- •Brain death on arrival in the participating centers;
- •Severe pre-trauma disability, defined as being dependent on other people;
- •Known prior history of sensibility to blood products or Cinryze;
- •Patients with a history of hereditary angioedema;
- •Patients with a history of thrombosis;
- •Pregnant women.
研究组 & 干预措施
C1-inhibitor
One dose 6000 IU C1-inhibitor intravenously
干预措施: C1 Inhibitor, Human (Drug)
Placebo
0.9% saline
干预措施: Placebo (Drug)
结局指标
主要结局
Therapy Intensity Level (TIL) Scale
时间窗: First four ICU days
TIL differentiated for various treatment modalities aimed at prevention or control of raised Intracranial Pressure (ICP) and/or for CPP management (0 to 38 points)
Glasgow Outcome Scale Extended (GOSE)
时间窗: At 6 months after trauma
Functional outcome (minimum score = 1, maximum score = 8)
Complication rate
时间窗: Up to 1 year
Adverse and serious adverse events related possibly related to study medication
次要结局
- Intracranial pressure (ICP) burden(First four ICU days)
- CT scan midline shift(Up to 1 year)
- Mortality(Up to 1 year after trauma)
- Glasgow Outcome Scale Extended (GOSE)(At discharge (an average of 14 days), 3 and 12 months after trauma)
- QoLiBri(At 3, 6 and 12 months after trauma)
- SF-36(At 3, 6 and 12 months after trauma)
- EQ-5D-5L(At 6 and 12 months after trauma)
- ICU length of stay(Up to 1 year)
- Ventilator days(Up to 1 year)
- Hospital length of stay(Up to 1 year)
- Hospital disposition(Up to 1 year)
- UCH-L1 and GFAP biomarkers(Baseline (Before adminstration of investigational product ) and 6, 12, 24, 48, 72 and 96 hours after adminstration of investigational product)
- Complement activation(Baseline (Before adminstration of investigational product ) and 6, 12, 24, 48, 72 and 96 hours after adminstration of investigational product)
- Coagulation cascade activation(Baseline (Before adminstration of investigational product ) and 6, 12, 24, 48, 72 and 96 hours after adminstration of investigational product)
- Inflammatory markers(Baseline (Before adminstration of investigational product ) and 6, 12, 24, 48, 72 and 96 hours after adminstration of investigational product)
研究者
wcpeul
Principal Investigator
Leiden University Medical Center