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Efficacy of VAS203 (Ronopterin) in Patients With Moderate and Severe Traumatic Brain Injury (NOSTRA-III)

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ClinicalTrials.gov Identifier: NCT02794168
Recruitment Status : Recruiting
First Posted : June 8, 2016
Last Update Posted : January 8, 2018
Sponsor:
Collaborator:
ICON plc
Information provided by (Responsible Party):
Vasopharm GmbH

May 31, 2016
June 8, 2016
January 8, 2018
June 2016
November 2018   (Final data collection date for primary outcome measure)
extended Glasgow Outcome Scale [ Time Frame: 6 months ]
clinical outcome questionnaire
Same as current
Complete list of historical versions of study NCT02794168 on ClinicalTrials.gov Archive Site
  • Quality of life after brain injury (QOLIBRI) [ Time Frame: 6 months ]
    clinical outcome questionnaire
  • QOLIBRI overall scale [ Time Frame: 6 months ]
    clinical outcome questionnaire
  • extended Glasgow Outcome Scale [ Time Frame: 3 months ]
    clinical outcome questionnaire
  • QOLIBRI overall scale [ Time Frame: 3 months ]
    clinical outcome questionnaire
  • Therapy Intensity Level [ Time Frame: 14 days ]
    Daily recording of score for therapeutic measures
  • Number of decompressive craniectomies [ Time Frame: 14 days ]
    Number of decompressive craniotomies on both hemispheres
Same as current
  • Adverse Events [ Time Frame: 14 days ]
    Number of adverse events related to treatment
  • Intracranial Pressure (ICP) and Cerebral Perfusion Pressure (CPP) [ Time Frame: 5 days ]
    Hourly recording of ICP and CPP
  • Renal function [ Time Frame: 14 days ]
    Number of patients exhibiting acute kidney injury according Acute Kidney Injury Network criteria
  • Mortality [ Time Frame: 6 Months ]
    Mortality 6 months after traumatic brain injury
Same as current
 
Efficacy of VAS203 (Ronopterin) in Patients With Moderate and Severe Traumatic Brain Injury
Efficacy of VAS203 (Ronopterin) in Patients With Moderate and Severe Traumatic Brain Injury - (NOSTRA Phase III Trial): A Confirmatory, Placebo-controlled, Randomised, Double Blind, Multi-centre Study
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.

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.

Interventional
Phase 3
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Traumatic Brain Injury
  • Drug: VAS203
    Treatment
    Other Name: Ronopterin
  • Drug: Saline
    Placebo
  • Experimental: VAS203 (Ronopterin)
    Intravenous infusion of 17 mg/kg VAS203 over 48 hours, daily dose 8.5 mg/kg
    Intervention: Drug: VAS203
  • Placebo Comparator: Saline
    Intravenous infusion of physiological saline over 48 hours
    Intervention: Drug: Saline
Stover JF, Belli A, Boret H, Bulters D, Sahuquillo J, Schmutzhard E, Zavala E, Ungerstedt U, Schinzel R, Tegtmeier F; NOSTRA Investigators. Nitric oxide synthase inhibition with the antipterin VAS203 improves outcome in moderate and severe traumatic brain injury: a placebo-controlled randomized Phase IIa trial (NOSTRA). J Neurotrauma. 2014 Oct 1;31(19):1599-606. doi: 10.1089/neu.2014.3344. Epub 2014 Jul 28.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
220
Same as current
November 2018
November 2018   (Final data collection date for primary outcome measure)

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
Sexes Eligible for Study: All
18 Years to 60 Years   (Adult)
No
Contact: Reinhard Schinzel, PhD +49 931 359099 ext 115 schinzel@vasopharm.de
Contact: Frank Tegtmeier, PhD +49 931 359099 ext 230 tegtmeier@vasopharm.de
Austria,   France,   Germany,   Spain,   United Kingdom
 
 
NCT02794168
VAS203/III/1/04
Yes
Not Provided
Plan to Share IPD: Undecided
Vasopharm GmbH
Vasopharm GmbH
ICON plc
Principal Investigator: Erich Schmutzhard, Prof. MD Medical University Innsbruck
Vasopharm GmbH
January 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP