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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
106
6000 IU C1-INH
0.9% saline
Leiden University Medical Center
Leiden, Netherlands
RECRUITINGErasmus Medical Center
Rotterdam, Netherlands
NOT_YET_RECRUITINGHaaglanden Medisch Centrum
The Hague, Netherlands
RECRUITINGTherapy Intensity Level (TIL) Scale
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)
Time frame: First four ICU days
Glasgow Outcome Scale Extended (GOSE)
Functional outcome (minimum score = 1, maximum score = 8)
Time frame: At 6 months after trauma
Complication rate
Adverse and serious adverse events related possibly related to study medication
Time frame: Up to 1 year
Intracranial pressure (ICP) burden
Minutes of ICP\>20 mm Hg
Time frame: First four ICU days
CT scan midline shift
in mm
Time frame: Up to 1 year
Mortality
Time frame: Up to 1 year after trauma
Glasgow Outcome Scale Extended (GOSE)
Functional outcome (minimum score = 1, maximum score = 8)
Time frame: At discharge (an average of 14 days), 3 and 12 months after trauma
QoLiBri
Quality of Life
Time frame: At 3, 6 and 12 months after trauma
SF-36
Health-related quality of life
Time frame: At 3, 6 and 12 months after trauma
EQ-5D-5L
Health-related quality of life
Time frame: At 6 and 12 months after trauma
ICU length of stay
in days
Time frame: Up to 1 year
Ventilator days
in days
Time frame: Up to 1 year
Hospital length of stay
in days
Time frame: Up to 1 year
Hospital disposition
Discharged to home, rehabilitation or nursery home
Time frame: Up to 1 year
UCH-L1 and GFAP biomarkers
Time frame: Baseline (Before adminstration of investigational product ) and 6, 12, 24, 48, 72 and 96 hours after adminstration of investigational product
Complement activation
WIESLAB, C3b/C, C4b/C, C5b-9 ELISA assays, CH50/AC50
Time frame: Baseline (Before adminstration of investigational product ) and 6, 12, 24, 48, 72 and 96 hours after adminstration of investigational product
Coagulation cascade activation
PT, aPPT, PLT, D-dimer, fibrinogen
Time frame: Baseline (Before adminstration of investigational product ) and 6, 12, 24, 48, 72 and 96 hours after adminstration of investigational product
Inflammatory markers
TNF-alpha, intraleukins
Time frame: Baseline (Before adminstration of investigational product ) and 6, 12, 24, 48, 72 and 96 hours after adminstration of investigational product
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