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Trial record 1 of 1 for:    NCT02794168
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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 : Active, not recruiting
First Posted : June 8, 2016
Last Update Posted : January 18, 2020
Sponsor:
Collaborator:
ICON plc
Information provided by (Responsible Party):
Vasopharm GmbH

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.

Condition or disease Intervention/treatment Phase
Traumatic Brain Injury Drug: VAS203 Drug: Saline Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 224 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : June 2016
Estimated Primary Completion Date : June 30, 2020
Estimated Study Completion Date : June 30, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: VAS203 (Ronopterin)
Intravenous infusion of 17 mg/kg VAS203 over 48 hours, daily dose 8.5 mg/kg
Drug: VAS203
Treatment
Other Name: Ronopterin

Placebo Comparator: Saline
Intravenous infusion of physiological saline over 48 hours
Drug: Saline
Placebo




Primary Outcome Measures :
  1. extended Glasgow Outcome Scale [ Time Frame: 6 months ]
    clinical outcome questionnaire


Secondary Outcome Measures :
  1. Quality of life after brain injury (QOLIBRI) [ Time Frame: 6 months ]
    clinical outcome questionnaire

  2. QOLIBRI overall scale [ Time Frame: 6 months ]
    clinical outcome questionnaire

  3. extended Glasgow Outcome Scale [ Time Frame: 3 months ]
    clinical outcome questionnaire

  4. QOLIBRI overall scale [ Time Frame: 3 months ]
    clinical outcome questionnaire

  5. Therapy Intensity Level [ Time Frame: 14 days ]
    Daily recording of score for therapeutic measures

  6. Number of decompressive craniectomies [ Time Frame: 14 days ]
    Number of decompressive craniotomies on both hemispheres


Other Outcome Measures:
  1. Adverse Events [ Time Frame: 14 days ]
    Number of adverse events related to treatment

  2. Intracranial Pressure (ICP) and Cerebral Perfusion Pressure (CPP) [ Time Frame: 5 days ]
    Hourly recording of ICP and CPP

  3. Renal function [ Time Frame: 14 days ]
    Number of patients exhibiting acute kidney injury according Acute Kidney Injury Network criteria

  4. Mortality [ Time Frame: 6 Months ]
    Mortality 6 months after traumatic brain injury



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02794168


Locations
Show Show 29 study locations
Sponsors and Collaborators
Vasopharm GmbH
ICON plc
Investigators
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Principal Investigator: Erich Schmutzhard, Prof. MD Medical University Innsbruck
Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Vasopharm GmbH
ClinicalTrials.gov Identifier: NCT02794168    
Other Study ID Numbers: VAS203/III/1/04
First Posted: June 8, 2016    Key Record Dates
Last Update Posted: January 18, 2020
Last Verified: January 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Additional relevant MeSH terms:
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Brain Injuries
Brain Injuries, Traumatic
Wounds and Injuries
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Craniocerebral Trauma
Trauma, Nervous System