NCT02794168

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.

Trial Health

93
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
224

participants targeted

Target at P25-P50 for phase_3

Timeline
Completed

Started Jun 2016

Typical duration for phase_3

Geographic Reach
5 countries

29 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

May 31, 2016

Completed
1 day until next milestone

Study Start

First participant enrolled

June 1, 2016

Completed
7 days until next milestone

First Posted

Study publicly available on registry

June 8, 2016

Completed
4.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 30, 2020

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

June 30, 2020

Completed
Last Updated

October 11, 2021

Status Verified

October 1, 2021

Enrollment Period

4.1 years

First QC Date

May 31, 2016

Last Update Submit

October 6, 2021

Conditions

Traumatic Brain Injury

Outcome Measures

Primary Outcomes (1)

  • extended Glasgow Outcome Scale

    clinical outcome questionnaire

    6 months

Secondary Outcomes (6)

  • Quality of life after brain injury (QOLIBRI)

    6 months

  • QOLIBRI overall scale

    6 months

  • extended Glasgow Outcome Scale

    3 months

  • QOLIBRI overall scale

    3 months

  • Therapy Intensity Level

    14 days

  • +1 more secondary outcomes

Other Outcomes (3)

  • Adverse Events

    14 days

  • Renal function

    14 days

  • Mortality

    6 Months

Study Arms (2)

VAS203 (Ronopterin)

EXPERIMENTAL

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

Drug: VAS203

Saline

PLACEBO COMPARATOR

Intravenous infusion of physiological saline over 48 hours

Drug: Saline

Interventions

VAS203DRUG

Treatment

Also known as: Ronopterin
VAS203 (Ronopterin)
SalineDRUG

Placebo

Saline

Eligibility Criteria

Age18 Years - 60 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64)

You may qualify if:

  • Written informed consent from patient's legal guardian or legal representative or deferred consent procedure, according to local requirements
  • years of age, inclusive
  • Expected to survive more than 24 hours after admission
  • Traumatic Brain Injury (TBI) within the last 18 hours (infusion must not start earlier than 6 hours after the injury)
  • TBI with Glasgow Coma Score (GCS) ≥ 3 requiring intracranial pressure (ICP) monitoring according to the assessment of the treating physician.
  • Catheter placement (intraventricular or intraparenchymal, only) for monitoring and management of increased ICP
  • Systolic blood pressure ≥ 100 mmHg
  • Females of child-bearing potential must have a negative pregnancy test

You may not qualify if:

  • Penetrating head injury (e.g. missile, stab wound)
  • Concurrent, but not pre-existing, spinal cord injury
  • Bilateral fixed and dilated pupil (\> 4 mm)
  • Cardiopulmonary resuscitation performed post injury, or extracranial injuries causing continuing bleeding likely to require multiple transfusions (\> 4 units red blood cells)
  • Coma due to an exclusive epidural hematoma (lucid interval and absence of structural brain damage on CT scan)
  • Coma suspected to be primarily due to other causes than head injury (e.g. drug overdose intoxication, drowning/near drowning)
  • Known or CT scan evidence of pre-existing major cerebral damage
  • Patients who cannot be monitored with regard to their recovery (eGOS-I and QOLIBRI)
  • Patients and relatives of patients who don´t understand/speak Spanish, or English, or French, or German
  • Decompressive craniectomy, planned prior to randomisation
  • Polytraumatic patients with Injury Severity Score non-head \> 18
  • Rhabdomyolysis with Creatine Kinase \> 5000 IU/L
  • Injuries to ascending aorta and/or carotid arteries and vertebral arteries
  • Serum creatinine values \> 1.2 mg/dL (106 µmol/L) (women), or \> 1.5 mg/dL (133 µmol/L) (men)
  • Estimated glomerular filtration rate (eGFR) \< 60 mL/min as calculated by Chronic Kidney Disease Epidemiology Collaboration Formula
  • +3 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (29)

Universitätsklinik für Neurochirurgie

Graz, 8036, Austria

Location

Neurologie und Neurochirurgie Medizinische Universität Innsbruck

Innsbruck, Austria

Location

Klinik für Allgemeine Anästhesie und Intensivmedizin AKH Wien

Vienna, Austria

Location

Hôpital Pellegrin Service de réanimation traumatologique et chirurgicale

Bordeaux, 33076, France

Location

Hopital Gabriel Montpied

Clermont-Ferrand, 63003, France

Location

Pôle Anesthésie Réanimation Douleur Urgence

Nîmes, France

Location

HIA Sainte-Anne Boulevard Sainte-Anne

Toulon, 83800, France

Location

Charite Virchow-Klinikum

Berlin, 13353, Germany

Location

Berufsgenossenschaftliche Kliniken Bergmannsheil Klinik für Neurochirurgie

Bochum, Germany

Location

Allgemeines Krankenhaus Celle Neurotraumatologie

Celle, Germany

Location

Universitätsklinikum Düsseldorf Neurochirurgische Klinik

Düsseldorf, Germany

Location

Klinik für Neurochirurgie Universität Frankfurt

Frankfurt, Germany

Location

Universitätsklinikum Göttingen Klinik für Neurochirurgie

Göttingen, Germany

Location

Berufsgenossenschaftliche Kliniken Bergmannstrost Halle Klinik für Neurochirurgie

Halle, Germany

Location

Universitätsklinikum Hamburg-Eppendorf Klinik und Poliklinik für Neurochirurgie

Hamburg, Germany

Location

Medizinische Hochschule Hannover Klinik für Neurochirurgie

Hanover, Germany

Location

Neurochirurgische Universitätsklinik Heidelberg

Heidelberg, Germany

Location

Universitätsklinikum des Saarlands

Homburg, 66421, Germany

Location

Universitätsklinikum Jena Klinik und Poliklinik für Neurochirurgie

Jena, Germany

Location

Universitätsklinikum Schleswig-Holstein Klinik für Neurochirurgie

Kiel, Germany

Location

Universitätsklinikum Leipzig Klinik und Poliklinik für Neurochirurgie

Leipzig, Germany

Location

Vall d'Hebron University Hospital Department of Neurosurgery

Barcelona, 08035, Spain

Location

Hospital General Universitario

Elche, Spain

Location

Hospital 12 de Octubre

Madrid, Spain

Location

Son Espases University Hospital

Palma, Spain

Location

Queen Elizabeth Hospital Birmingham

Birmingham, United Kingdom

Location

NHS Lothian University of Edinburgh

Edinburgh, United Kingdom

Location

Kings College Hospital London

London, United Kingdom

Location

Southampton University Hospital Division of Clinical Neurosciences

Southampton, United Kingdom

Location

Related Publications (2)

  • 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.

    PMID: 24831445BACKGROUND

  • 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.

    PMID: 31937347DERIVED

MeSH Terms

Conditions

Brain Injuries, Traumatic

Interventions

4-amino-tetrahydrobiopterinSodium Chloride

Condition Hierarchy (Ancestors)

Brain InjuriesBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesCraniocerebral TraumaTrauma, Nervous SystemWounds and Injuries

Intervention Hierarchy (Ancestors)

ChloridesHydrochloric AcidChlorine CompoundsInorganic ChemicalsSodium Compounds

Study Officials

  • Erich Schmutzhard, Prof. MD

    Medical University Innsbruck

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

May 31, 2016

First Posted

June 8, 2016

Study Start

June 1, 2016

Primary Completion

June 30, 2020

Study Completion

June 30, 2020

Last Updated

October 11, 2021

Record last verified: 2021-10

Locations

ES(4)AU(3)GB(4)DE(14)FR(4)