An interventional study of Optimal cerebral perfusion pressure in Traumatic Brain Injury, Severe Traumatic Brain Injury and Intracranial Pressure, sponsored by Maastricht University Medical Center. Not yet recruiting at 4 sites in Netherlands. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-09-28.
Sponsored by Maastricht University Medical Center · Not applicable, Interventional, and Prevention
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.
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.
Main study parameters/endpoints:
The primary outcome of this effectiviness study will be the cumulative release of blood biomarker Glial Fibrillary Acidic Protein (GFAP) up to fourteen days of ICU admission, quantified as the area under the curve (AUC) in both groups. GFAP is selected because its relatively short half-life makes it particularly sensitive to secondary brain injury, as increases or sustained elevations reflect ongoing damage rather than the initial trauma. In the present study, the hypothesis is that patients managed with CPPopt-guided therapy will show lower cumulative GFAP release compared to patients receiving standard guideline-based CPP management. A lower cumulative GFAP level would indicate less secondary neuronal injury during the critical early phase after TBI.
Secondary study parameters are
Exclusion Criteria:
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.
Other: Optimal cerebral perfusion pressure
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.
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.
Also known as: CPPopt
Cumulative concentration of blood biomarker Glial Fibrillary Acidic Protein (GFAP) up to 14 days during 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.
Time frame: The first 14 days of ICU admission
Cumulative concentrations of biomarkers NSE, UCH-L1, S100B, Tau and NfL up to 14 days of ICU admission
The cumulative release of five additional brain injury biomarkers: Neuron Specific Enolase (NSE), Ubiquitin C-terminal hydrolase L1 (UCH-L1), S100 calcium-binding protein B (S100B), Tau, and Neu-rofilament light chain (NfL) 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.
Time frame: the first 14 days of ICU admission
Progression of cerebral edema on CT imaging based on size of hypodense regions in sequential CT scans
Cerebral edema progression will be quantified by comparing brain CT scans obtained at admission with follow-up scans within the first five days of ICU admission (performed when clinically indicated).
Time frame: first five days of ICU admission
Daily Therapy Intensity Level (TIL) score
Daily intracranial hypertenstion Therapy Intensity Level (TIL) score during the first five days on ICU to test whether our intervention reduces the need for aggressive treatment of increased ICP. Individual ICP-targeting therapies were assigned a score based on published estimates of their relative efficacy and risks of morbidity. The TIL includes eight ICP-treatment modalities, termed items. The maximum score is 38, with a higher score indicating that a patient is receiving more complex, aggressive, or frequent treatments.
Time frame: first five days on ICU
Mean daily Pressure Reactivity Index (PRx) values
Mean daily Pressure Reactivity Index (PRx) values will be calculated as a global measure of cerebral autoregulation. PRx is defined as the moving correlation coefficient between slow waves of ABP and ICP, with more positive values indicating impaired autoregulation.
Time frame: First 5 days on ICU
Frequency and duration of CPP outside safety limits (50-100 mmHg)
Frequency and cumulative duration of CPP excursions outside the predefined safety limits (CPP between 50 mmHg and 100 mmHg) during the first five days will be recorded for each patient. These data will be used to evaluate the safety of CPPopt guided management compared to standard care, by quantifying both the number and total time of CPP deviations beyond clinically acceptable thresholds.
Time frame: First 5 days on ICU
Glasgow Coma Score at the moment of intensive care unit discharge
Glasgow Coma Score at ICU discharge will be recorded as an early indicator of patient outcome. The Glasgow Coma Scale (GCS) is a clinical diagnostic tool widely used since the 1970s to roughly assess an injured person's level of brain damage. The GCS diagnosis is based on a patient's ability to respond and interact with three kinds of behaviour: eye movements, speech, and other body motions. A GCS score can range from 3 (completely unresponsive) to 15 (responsive). The higher the value, the better the neurological state.
Time frame: 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
ICU mortality will also be recorded as an early indicator of patient outcome. Patients dying will be registered as "dead", patients who are alive at ICU discharge will be registered as "survival".
Time frame: 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
Non-invasive near-infrared spectroscopy (NIRS) values will be recorded using bifrontal sensors to estimate cerebral oxygenation. NIRS provides a non-invasive measure of cerebral perfusion, as changes in cerebral oxygenation correlate with changes in cerebral blood flow
Time frame: First 5 days on ICU
Progression of cerebral hematoma on CT imaging based on size of hyperdense regions in sequential CT scans
Cerebral hematoma progression will be quantified by comparing brain CT scans obtained at admission with follow-up scans within the first five days of ICU admission (performed when clinically indicated).
Time frame: First 5 days of ICU admission
Plan to share: Undecided
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Maastricht University Medical Center