CPPopt Guided Therapy: Assessment of Target Effectiveness - II
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 62
- 试验地点
- 4
- 主要终点
- Cumulative concentration of blood biomarker Glial Fibrillary Acidic Protein (GFAP) up to 14 days during ICU admission
研究概览
简要总结
After severe traumatic brain injury, adequate blood flow to the brain is essential for recovery. This depends on arterial blood pressure, yet intensive care units apply fixed targets to all patients - treating every brain and patient the same. This study aims to change that. With new technology, 'optimal' blood pressure can be determined for each individual brain and treatment can be tailored accordingly. This personalized approach to neurocritical care has never been tested in a randomized controlled study before. If effective in showing reduced brain damage biomarkers, it will fundamentally transform brain injury treatment and dramatically improve recovery outcomes for patients worldwide.
详细描述
Rationale: In traumatic brain injury patients with intracranial pressure monitoring (TBIicp), individualized optimal cerebral perfusion pressure (also called CPPopt) can be determined based on continuous cerebral autoregulation information. In a 2021 study, CPPopt guided management has been demonstrated to be both feasible and safe in clinical practice. This study was performed in 4 European countries and coordinated by the Intensive care department in Maastricht. CPPopt guided management aims to minimize harm from global or regional hypo- or hyperperfusion of the injured brain compared to the classical treatment. Classical treatment maintains cerebral perfusion pressure (CPP) at a fixed, pre-determined range of 60-70 mmHg in all patients during the entire period the intracranial pressure (ICP) is monitored. CPP is calculated as the arterial blood pressure (ABP) minus the ICP. CPP targets are obtained by manipulating ICP (if elevated) or ABP. Observational data suggests that management of CPP above CPPopt is associated with severe disability, and below CPPopt with mortality. However, there is no prospective evidence to support the effectiviness of CPPopt guided management and its effect on clinical outcome in severe TBIicp patients.
Objective: To determine whether individualized CPPopt guided management reduces secondary brain injury in patients with severe traumatic brain injury requiring intracranial pressure monitoring, as reflected by lower concentrations of brain injury-related biomarkers during the first fourteen days of intensive care unit (ICU) admission, compared with standard guideline-based CPP management.
Study design: Multicenter, randomized, controlled trial to test the effectiviness of CPPopt guided management in 4 Dutch hospitals.
Study population: Adult patients with severe traumatic brain injury and intracranial pressure monitoring (TBIicp). 62 patients will be included in a 2 year period.
Intervention: The intervention group will receive CPPopt guided management with updated CPPopt targets every 4 hours, for a maximum duration of 5 days. The control group will receive standard of care CPP management formulated as a CPP between 60-70 mmHg according to Brain Trauma Foundation (BTF) guideline.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
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
- •Adult (>18 years old)
- •Severe TBI requiring ICP-directed therapy for at least 24 hrs on the assessment of the recruiting intensive care team and/or attending neurosurgeon
- •Start randomization within 24 hrs after ICU admission.
排除标准
- •Known pregnancy
- •Moribund at presentation (e.g. bilaterally absent pupillary responses)
- •Patients with a primary decompressive craniectomy
- •Failure to get final written informed consent
研究组 & 干预措施
CPPopt treatment
The CPPopt treatment group will receive management according to the Brain Trauma Foundation (BTF) guidelines, except for the targeted cerebral perfusion pressure. Here, the calculated "optimal cerebral perfusion pressure (CPPopt)" will be targeted, with updated CPPopt targets every 4 hours. CPPopt treatment will be performed for a maximum of 5 days. If a patient still requires ICP treatment after 5 days, the standard, guideline-based treatment will be followed. CPPopt treatment can be shorter than 5 days, if ICP measurement is no longer required, if a patients wakes up, or if a patient dies.
干预措施: Optimal cerebral perfusion pressure (Other)
Control group
The intervention group will receive standard brain trauma management according to the Brain Trauma Foundation (BTF) guidelines, including the standard cerebral perfusion pressure target of 60-70 mmHg.
结局指标
主要结局
Cumulative concentration of blood biomarker Glial Fibrillary Acidic Protein (GFAP) up to 14 days during ICU admission
时间窗: The first 14 days of ICU admission
The cumulative release of blood biomarker Glial Fibrillary Acidic Protein (GFAP) will be determined at ICU admission, and on day 1-5, 7 and 14 after ICU admission, but only as long as a patient is still on the ICU and has vascular access. GFAP will be quantified as the area under the curve (AUC) in both groups.
Cumulative concentration of blood biomarker Glial Fibrillary Acidic Protein (GFAP) during first 5 days of ICU admission
时间窗: The first 5 days of ICU admission
The cumulative release of blood biomarker Glial Fibrillary Acidic Protein (GFAP) over the first five days of ICU admission, quantified as the area under the curve (AUC) in both groups
次要结局
- Progression of cerebral edema on CT imaging based on size of hypodense regions in sequential CT scans(first five days of ICU admission)
- Daily Therapy Intensity Level (TIL) score(first five days on ICU)
- Mean daily Pressure Reactivity Index (PRx) values(First 5 days on ICU)
- Frequency and duration of CPP outside safety limits (50-100 mmHg)(First 5 days on ICU)
- Non-invasive near-infrared spectroscopy (NIRS) values(First 5 days on ICU)
- Progression of cerebral hematoma on CT imaging based on size of hyperdense regions in sequential CT scans(First 5 days of ICU admission)
- Cumulative concentrations of biomarkers NSE, UCH-L1, S100B, Tau and NfL up to 14 days of ICU admission(the first 14 days of ICU admission)
- Cumulative concentrations of biomarkers NSE, UCH-L1, S100B, Tau and NfL during first 5 days of ICU admission(the first 5 days of ICU admission)
- Progression of cerebral edema on CT imaging based on size of hypodense regions in sequential CT scans(first five days of ICU admission)
- Daily Therapy Intensity Level (TIL) score(first five days on ICU)
- Mean daily Pressure Reactivity Index (PRx) values(First 5 days on ICU)
- Frequency and duration of CPP outside safety limits (50-100 mmHg)(First 5 days on ICU)
- Glasgow Coma Score at the moment of intensive care unit discharge(At the moment a patient is discharged from ICU, assessed up to 2 months after ICU admission)
- ICU mortality at the moment of ICU discharge(At time of death, or if survival: at the moment the patient is discharged from ICU, assessed up to 2 months after ICU admission)
- Non-invasive near-infrared spectroscopy (NIRS) values(First 5 days on ICU)
- Progression of cerebral hematoma on CT imaging based on size of hyperdense regions in sequential CT scans(First 5 days of ICU admission)