Traumatic Brain Injury
Conditions
Brief summary
This study evaluates the efficacy of an infusion of Ronopterin (VAS203) on clinical outcome in patients with moderate and severe traumatic brain injury. Half of the participants will receive Ronopterin (VAS203), while the other half will receive placebo.
Detailed description
Severe and moderate traumatic brain injury (TBI) constitutes a major health problem. TBI is the leading cause of death and disability among young adults in developed countries, and the incidence in the elderly population is increasing. Neurological damage after TBI is caused not only by the accident itself, but evolves afterwards. The posttraumatic secondary injury includes - among others - inflammation and oedema formation with subsequent increase of intracranial pressure. A key molecule in these processes is the gas nitric oxide, which is produced in excess during neuroinflammation. Ronopterin (VAS203) is an inhibitor of nitric oxide synthase. Ronopterin reduces excess nitric oxide production and subsequent secondary injury.
Interventions
DRUGVAS203
Treatment
DRUGSaline
Placebo
Sponsors
ICON plc
veriNOS operations GmbH
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
1. Written informed consent from patient's legal guardian or legal representative or deferred consent procedure, according to local requirements 2. 18 - 60 years of age, inclusive 3. Expected to survive more than 24 hours after admission 4. Traumatic Brain Injury (TBI) within the last 18 hours (infusion must not start earlier than 6 hours after the injury) 5. TBI with Glasgow Coma Score (GCS) ≥ 3 requiring intracranial pressure (ICP) monitoring according to the assessment of the treating physician. 6. Catheter placement (intraventricular or intraparenchymal, only) for monitoring and management of increased ICP 7. Systolic blood pressure ≥ 100 mmHg 8. Females of child-bearing potential must have a negative pregnancy test
Exclusion criteria
1. Penetrating head injury (e.g. missile, stab wound) 2. Concurrent, but not pre-existing, spinal cord injury 3. Bilateral fixed and dilated pupil (\> 4 mm) 4. Cardiopulmonary resuscitation performed post injury, or extracranial injuries causing continuing bleeding likely to require multiple transfusions (\> 4 units red blood cells) 5. Coma due to an exclusive epidural hematoma (lucid interval and absence of structural brain damage on CT scan) 6. Coma suspected to be primarily due to other causes than head injury (e.g. drug overdose intoxication, drowning/near drowning) 7. Known or CT scan evidence of pre-existing major cerebral damage 8. Patients who cannot be monitored with regard to their recovery (eGOS-I and QOLIBRI) 9. Patients and relatives of patients who don´t understand/speak Spanish, or English, or French, or German 10. Decompressive craniectomy, planned prior to randomisation 11. Polytraumatic patients with Injury Severity Score non-head \> 18 12. Rhabdomyolysis with Creatine Kinase \> 5000 IU/L 13. Injuries to ascending aorta and/or carotid arteries and vertebral arteries 14. Serum creatinine values \> 1.2 mg/dL (106 µmol/L) (women), or \> 1.5 mg/dL (133 µmol/L) (men) 15. Estimated glomerular filtration rate (eGFR) \< 60 mL/min as calculated by Chronic Kidney Disease Epidemiology Collaboration Formula 16. BMI \< 18.5 kg/m2 and \> 40 kg/m2, Body weight \> 110 kg 17. Any severe concomitant condition (cancer; hematologic, renal, hepatic, coronary disease; major psychiatric disorder; alcohol or drug abuse), that can be ascertained at admission 18. Known to have received an experimental drug within 4 weeks prior to current injury
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| extended Glasgow Outcome Scale | 6 months | clinical outcome questionnaire |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| QOLIBRI overall scale | 6 months | clinical outcome questionnaire |
| extended Glasgow Outcome Scale | 3 months | clinical outcome questionnaire |
| Therapy Intensity Level | 14 days | Daily recording of score for therapeutic measures |
| Number of decompressive craniectomies | 14 days | Number of decompressive craniotomies on both hemispheres |
| Quality of life after brain injury (QOLIBRI) | 6 months | clinical outcome questionnaire |
Other
| Measure | Time frame | Description |
|---|---|---|
| Mortality | 6 Months | Mortality 6 months after traumatic brain injury |
| Renal function | 14 days | Number of patients exhibiting acute kidney injury according Acute Kidney Injury Network criteria |
| Adverse Events | 14 days | Number of adverse events related to treatment |
Countries
Austria, France, Germany, Spain, United Kingdom
Outcome results
None listed