Trauma, Head, Traumatic Brain Injury
Conditions
Keywords
Traumatic Brain Injury, C1-inhibitor, Neuroinflammation, Efficacy, Safety
Brief summary
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.
Interventions
DRUGC1 Inhibitor, Human
6000 IU C1-INH
DRUGPlacebo
0.9% saline
Sponsors
Netherlands Brain Foundation
Takeda
Leiden University Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 64 Years
Healthy volunteers
No
Inclusion criteria
* 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;
Exclusion criteria
* 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Therapy Intensity Level (TIL) Scale | 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) | At 6 months after trauma | Functional outcome (minimum score = 1, maximum score = 8) |
| Complication rate | Up to 1 year | Adverse and serious adverse events related possibly related to study medication |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Glasgow Outcome Scale Extended (GOSE) | At discharge (an average of 14 days), 3 and 12 months after trauma | Functional outcome (minimum score = 1, maximum score = 8) |
| QoLiBri | At 3, 6 and 12 months after trauma | Quality of Life |
| SF-36 | At 3, 6 and 12 months after trauma | Health-related quality of life |
| EQ-5D-5L | At 6 and 12 months after trauma | Health-related quality of life |
| ICU length of stay | Up to 1 year | in days |
| Ventilator days | Up to 1 year | in days |
| Intracranial pressure (ICP) burden | First four ICU days | Minutes of ICP\>20 mm Hg |
| Hospital disposition | Up to 1 year | Discharged to home, rehabilitation or nursery home |
| 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 | WIESLAB, C3b/C, C4b/C, C5b-9 ELISA assays, CH50/AC50 |
| Coagulation cascade activation | Baseline (Before adminstration of investigational product ) and 6, 12, 24, 48, 72 and 96 hours after adminstration of investigational product | PT, aPPT, PLT, D-dimer, fibrinogen |
| Inflammatory markers | Baseline (Before adminstration of investigational product ) and 6, 12, 24, 48, 72 and 96 hours after adminstration of investigational product | TNF-alpha, intraleukins |
| Hospital length of stay | Up to 1 year | in days |
| CT scan midline shift | Up to 1 year | in mm |
| Mortality | Up to 1 year after trauma | — |
Countries
Netherlands
Contacts
Primary ContactInge van Erp, BSc
Outcome results
None listed