Traumatic Brain InjuryPhase 3NOSTRA-IIINCT02794168
Efficacy of VAS203 (Ronopterin) in Patients With Moderate and Severe Traumatic Brain Injury
A Phase 3 study testing VAS203 and Saline in people with Traumatic Brain Injury, run by veriNOS operations GmbH at 29 sites in 5 countries.
Trial 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 more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Traumatic Brain Injury
- What is being tested?
- VAS203 and Saline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 224 participants
- Where
- 29 sitesin 5 countries
- Study dates
- Jun 2016to 30 Jun 2020
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Written informed consent from patient's legal guardian or legal representative or deferred consent procedure, according to local requirements
- 18 - 60 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
Who cannot join
- 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)
Show all 18Show fewer
- 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
- BMI < 18.5 kg/m2 and > 40 kg/m2, Body weight > 110 kg
- Any severe concomitant condition (cancer; hematologic, renal, hepatic, coronary disease; major psychiatric disorder; alcohol or drug abuse), that can be ascertained at admission
- Known to have received an experimental drug within 4 weeks prior to current injury
Trial locations and contacts
29 sites in 5 countries.
29 sites in 5 countries
Germany14 sites
Charite Virchow-Klinikum
Berlin, 13353
Berufsgenossenschaftliche Kliniken Bergmannsheil Klinik für Neurochirurgie
Bochum
Allgemeines Krankenhaus Celle Neurotraumatologie
Celle
Universitätsklinikum Düsseldorf Neurochirurgische Klinik
Düsseldorf
Klinik für Neurochirurgie Universität Frankfurt
Frankfurt
Universitätsklinikum Göttingen Klinik für Neurochirurgie
Göttingen
Berufsgenossenschaftliche Kliniken Bergmannstrost Halle Klinik für Neurochirurgie
Halle
Universitätsklinikum Hamburg-Eppendorf Klinik und Poliklinik für Neurochirurgie
Hamburg
Medizinische Hochschule Hannover Klinik für Neurochirurgie
Hanover
Neurochirurgische Universitätsklinik Heidelberg
Heidelberg
Universitätsklinikum des Saarlands
Homburg, 66421
Universitätsklinikum Jena Klinik und Poliklinik für Neurochirurgie
Jena
Universitätsklinikum Schleswig-Holstein Klinik für Neurochirurgie
Kiel
Universitätsklinikum Leipzig Klinik und Poliklinik für Neurochirurgie
Leipzig
France4 sites
Hôpital Pellegrin Service de réanimation traumatologique et chirurgicale
Bordeaux, 33076
Hopital Gabriel Montpied
Clermont-Ferrand, 63003
Pôle Anesthésie Réanimation Douleur Urgence
Nîmes
HIA Sainte-Anne Boulevard Sainte-Anne
Toulon, 83800
Spain4 sites
Vall d'Hebron University Hospital Department of Neurosurgery
Barcelona, 08035
Hospital General Universitario
Elche
Hospital 12 de Octubre
Madrid
Son Espases University Hospital
Palma
United Kingdom4 sites
Queen Elizabeth Hospital Birmingham
Birmingham
NHS Lothian University of Edinburgh
Edinburgh
Kings College Hospital London
London
Southampton University Hospital Division of Clinical Neurosciences
Southampton
Austria3 sites
Universitätsklinik für Neurochirurgie
Graz, 8036
Neurologie und Neurochirurgie Medizinische Universität Innsbruck
Innsbruck
Klinik für Allgemeine Anästhesie und Intensivmedizin AKH Wien
Vienna
About this study
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
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.
- Conditions
- Traumatic Brain Injury
- Being tested
- VAS203, Saline
- Medical subject headings
- Brain Injuries, Traumatic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VAS203Drug
Also called Ronopterin
Treatment
SalineDrug
Placebo
| Study group | Role | What they receive |
|---|---|---|
| VAS203 (Ronopterin) | Experimental | Intravenous infusion of 17 mg/kg VAS203 over 48 hours, daily dose 8.5 mg/kg Receives: Drug: VAS203 |
| Saline | Placebo comparator | Intravenous infusion of physiological saline over 48 hours Receives: Drug: Saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
extended Glasgow Outcome Scale
clinical outcome questionnaire
Measured: 6 months
Secondary outcomes (6)
Quality of life after brain injury (QOLIBRI)
clinical outcome questionnaire
Measured: 6 months
QOLIBRI overall scale
clinical outcome questionnaire
Measured: 6 months
extended Glasgow Outcome Scale
clinical outcome questionnaire
Measured: 3 months
QOLIBRI overall scale
clinical outcome questionnaire
Measured: 3 months
Therapy Intensity Level
Daily recording of score for therapeutic measures
Measured: 14 days
Number of decompressive craniectomies
Number of decompressive craniotomies on both hemispheres
Measured: 14 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jun 2016 (estimated)
- Study startJun 2016
- Primary completion30 Jun 2020
- Study completion30 Jun 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Traumatic Brain InjuryStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 224 participants (actual)
Sponsor and investigators
- Lead sponsor
- veriNOS operations GmbH
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- ICON plc
- Responsible party
- Sponsor
- Investigators
- Erich Schmutzhard, Prof. MD, Principal investigator, Medical University Innsbruck
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02794168
- Sponsor's protocol ID
- VAS203/III/1/04
- Acronym
- NOSTRA-III
- Status last verified
- Oct 2021
- First submitted
- 31 May 2016
- Last updated
- 11 Oct 2021
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided
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 24831445Tegtmeier 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.
PubMed 31937347
Study at a glance
From the registry record, last updated by the sponsor on 11 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02794168
- Acronym / sponsor ID
- NOSTRA-III / VAS203/III/1/04
- Conditions
- Traumatic Brain Injury
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 224 participants (actual)
- Lead sponsor
- veriNOS operations GmbHIndustry (pharma, biotech, devices)
- Collaborators
- ICON plc
- Study start
- Jun 2016 (actual)
- Primary completion
- 30 Jun 2020 (actual)
- Study completion
- 30 Jun 2020 (actual)
- First posted
- 8 Jun 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| VAS203 (Ronopterin) | Experimental | Drug: VAS203Intravenous infusion of 17 mg/kg VAS203 over 48 hours, daily dose 8.5 mg/kg |
| Saline | Placebo comparator | Drug: SalineIntravenous infusion of physiological saline over 48 hours |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- Written informed consent from patient's legal guardian or legal representative or deferred consent procedure, according to local requirements
- 18 - 60 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.
Key exclusion criteria (18 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| VAS203Also: RonopterinTreatment | Drug | VAS203 (Ronopterin) |
| SalinePlacebo | Drug | Saline |
Primary outcome
extended Glasgow Outcome Scale
Time frame: 6 months
clinical outcome questionnaire
6 secondary outcomes
Quality of life after brain injury (QOLIBRI)
Time frame: 6 months
QOLIBRI overall scale
Time frame: 6 months
extended Glasgow Outcome Scale
Time frame: 3 months
QOLIBRI overall scale
Time frame: 3 months
Therapy Intensity Level
Time frame: 14 days
Number of decompressive craniectomies
Time frame: 14 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Oct 2021.
- Background: PubMed 24831445Stover 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.
- Derived from this study: PubMed 31937347Tegtmeier 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.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Erich Schmutzhard, Prof. MD principal investigator
Medical University Innsbruck
29 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing VAS203 and Saline in people with Traumatic Brain Injury, run by veriNOS operations GmbH at 29 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 29 sites in Germany, France, Spain, United Kingdom, Austria. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
extended Glasgow Outcome Scale (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02794168, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Oct 2021.