CClinicalTrials.gg
Sign In
CompletedNCT02794168NOSTRA-IIIUpdated Oct 11, 2021

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

A Phase 3 interventional study of VAS203 and Saline in Traumatic Brain Injury, sponsored by veriNOS operations GmbH. Completed at 29 sites in 5 countries. Open to participants aged 18 Years to 60 Years. Per ClinicalTrials.gov, last updated 2021-10-11.

Sponsored by veriNOS operations GmbH · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
224
Allocation
Randomized
Ages
18 Years to 60 Years
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • Traumatic Brain Injury
03

In context

Brain Injuries

2,113 studies on the registry are indexed under Brain Injuries; 385 are open to participants now.

This study's enrollment of 224 is above the median of 48 across 1,331 interventional studies indexed under Brain Injuries.

Browse Brain Injuries studies →

Lead sponsor

veriNOS operations GmbH is the lead sponsor of 3 studies on the registry; none are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 60 Years
Sexes eligible
All
Accepts 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

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
05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Double (Participant, Investigator)
Enrollment
224 participants (actual)

Study arms

  • Experimental
    VAS203 (Ronopterin)

    Intravenous infusion of 17 mg/kg VAS203 over 48 hours, daily dose 8.5 mg/kg

    Drug: VAS203

  • Placebo comparator
    Saline

    Intravenous infusion of physiological saline over 48 hours

    Drug: Saline

Interventions

  • DrugVAS203

    Treatment

    Also known as: Ronopterin

  • DrugSaline

    Placebo

06

What researchers measure

Primary outcomes

  1. extended Glasgow Outcome Scale

    clinical outcome questionnaire

    Time frame: 6 months

Secondary outcomes

  1. Quality of life after brain injury (QOLIBRI)

    clinical outcome questionnaire

    Time frame: 6 months

  2. QOLIBRI overall scale

    clinical outcome questionnaire

    Time frame: 6 months

  3. extended Glasgow Outcome Scale

    clinical outcome questionnaire

    Time frame: 3 months

  4. QOLIBRI overall scale

    clinical outcome questionnaire

    Time frame: 3 months

  5. Therapy Intensity Level

    Daily recording of score for therapeutic measures

    Time frame: 14 days

  6. Number of decompressive craniectomies

    Number of decompressive craniotomies on both hemispheres

    Time frame: 14 days

Other outcomes

  1. Adverse Events

    Number of adverse events related to treatment

    Time frame: 14 days

  2. Renal function

    Number of patients exhibiting acute kidney injury according Acute Kidney Injury Network criteria

    Time frame: 14 days

  3. Mortality

    Mortality 6 months after traumatic brain injury

    Time frame: 6 Months

07

Study locations

29 sites
  • Universitätsklinik für Neurochirurgie
    Graz, 8036, Austria
  • Neurologie und Neurochirurgie Medizinische Universität Innsbruck
    Innsbruck, Austria
  • Klinik für Allgemeine Anästhesie und Intensivmedizin AKH Wien
    Wien, Austria
  • Hôpital Pellegrin Service de réanimation traumatologique et chirurgicale
    Bordeaux, 33076, France
  • Hopital Gabriel Montpied
    Clermont-Ferrand, 63003, France
  • Pôle Anesthésie Réanimation Douleur Urgence
    Nimes, France
  • HIA Sainte-Anne Boulevard Sainte-Anne
    Toulon, 83800, France
  • Charite Virchow-Klinikum
    Berlin, 13353, Germany
  • Berufsgenossenschaftliche Kliniken Bergmannsheil Klinik für Neurochirurgie
    Bochum, Germany
  • Allgemeines Krankenhaus Celle Neurotraumatologie
    Celle, Germany
  • Universitätsklinikum Düsseldorf Neurochirurgische Klinik
    Düsseldorf, Germany
  • Klinik für Neurochirurgie Universität Frankfurt
    Frankfurt, Germany
  • Universitätsklinikum Göttingen Klinik für Neurochirurgie
    Göttingen, Germany
  • Berufsgenossenschaftliche Kliniken Bergmannstrost Halle Klinik für Neurochirurgie
    Halle, Germany
  • Universitätsklinikum Hamburg-Eppendorf Klinik und Poliklinik für Neurochirurgie
    Hamburg, Germany
  • Medizinische Hochschule Hannover Klinik für Neurochirurgie
    Hannover, Germany
  • Neurochirurgische Universitätsklinik Heidelberg
    Heidelberg, Germany
  • Universitätsklinikum des Saarlands
    Homburg, 66421, Germany
  • Universitätsklinikum Jena Klinik und Poliklinik für Neurochirurgie
    Jena, Germany
  • Universitätsklinikum Schleswig-Holstein Klinik für Neurochirurgie
    Kiel, Germany
  • Universitätsklinikum Leipzig Klinik und Poliklinik für Neurochirurgie
    Leipzig, Germany
  • Vall d'Hebron University Hospital Department of Neurosurgery
    Barcelona, 08035, Spain
  • Hospital General Universitario
    Elche, Spain
  • Hospital 12 de Octubre
    Madrid, Spain
  • Son Espases University Hospital
    Palma, Spain
  • Queen Elizabeth Hospital Birmingham
    Birmingham, United Kingdom
  • NHS Lothian University of Edinburgh
    Edinburgh, United Kingdom
  • Kings College Hospital London
    London, United Kingdom
  • Southampton University Hospital Division of Clinical Neurosciences
    Southampton, United Kingdom
08

References and documents

Publications

  • 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. PubMed 24831445 ↗
  • Tegtmeier F, Schinzel R, Beer R, Bulters D, LeFrant JY, Sahuquillo J, Unterberg A, Andrews P, Belli A, Ibanez J, Lagares A, Mokry M, Willschke H, Fluh C, Schmutzhard E; NOSTRA Investigators. Efficacy of Ronopterin (VAS203) in Patients with Moderate and Severe Traumatic Brain Injury (NOSTRA phase III trial): study protocol of a confirmatory, placebo-controlled, randomised, double blind, multi-centre study. Trials. 2020 Jan 14;21(1):80. doi: 10.1186/s13063-019-3965-4. Erratum In: Trials. 2020 Feb 12;21(1):172. doi: 10.1186/s13063-020-4107-8. PubMed 31937347 ↗

Individual participant data

Plan to share: Undecided

09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Oct 11, 2021, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT02794168
Lead sponsor
veriNOS operations GmbH
Collaborators
ICON plc
Responsible party
Sponsor
First posted
Jun 8, 2016
Start date
Jun 2016
Primary completion
Jun 30, 2020
Completion
Jun 30, 2020
Last update
Oct 11, 2021

Study contacts

Erich Schmutzhard, Prof. MD
principal investigator · Medical University Innsbruck

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Oct 2021. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Other studies in this condition

Brain Injuries→

Other studies from this sponsor

veriNOS operations GmbH

Start the discussion