Traumatic Brain InjuryPhase 2NOSTRANCT02012582
Phase 2 a Study to Assess Safety and Pharmacokinetics of VAS203 in Patients With Traumatic Brain Injury
A Phase 2 study testing VAS203 and Saline in people with Traumatic Brain Injury, run by veriNOS operations GmbH at 6 sites in 5 countries.
Trial summary
In the exploratory multi-center Phase 2 a study safety, tolerability, pharmacodynamics and pharmacokinetics of the Nitric Oxide Synthase inhibitor VAS203 is assessed in patients with moderate and severe traumatic brain injury. Read more about this study
- Who is it for?
- Ages 18 to 65 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
- 32 participants
- Where
- 6 sitesin 5 countries
- Study dates
- Nov 2009to Sep 2012
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Written informed consent from patient's legal guardian or legal representative
- 18 - 65 years of age, inclusive
- Head trauma within the last 12 hours
- Traumatic brain injury with Glasgow Coma Score (GCS) ≥ 5 and that requires ICP monitoring
- Catheter placement for monitoring and management of increased ICP
- Microdialysis probe placement in penumbra zone or ipsilateral to contusion if focal
- 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)
- Not expected to survive more than 24 hours after admission
- Concurrent, but not pre-existing, spinal cord injury
- Unilateral and bilateral fixed and dilated pupil (> 4 mm)
- Cardiopulmonary resuscitation performed post injury
- continuing bleeding likely to require multiple transfusions (> 4 units red blood cells)
Show all 18Show fewer
- Coma due to a "pure" 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)
- Known or CT scan evidence of pre-existing major cerebral damage
- Decompressive craniectomy, planned prior to randomization
- Polytraumatic patients with Injury Severity Score > 25, or rhabdomyolysis
- Injuries to ascending aorta and/or carotid arteries
- serum creatinine values > 1.5 mg/dL
- estimated Glomerular Filtration Rate < 60 ml/min (MDRD-formula)
- body mass index (BMI) > 35, Body weight > 120 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
- Administration of > 100 ml of contrast media containing iodine
Trial locations and contacts
6 sites in 5 countries.
6 sites in 5 countries
Spain2 sites
Vall d'Hebron University Hospital Department of Neurosurgery
Barcelona, 08035
Hospital Clinic University of Barcelona Surgical Intensive Care Unit
Barcelona, 08036
Austria1 site
Medical University Innsbruck Department of Neurology
Innsbruck, 6020
Switzerland1 site
University Hospital Zuerich Surgical Intensive Care
Zurich, 8091
United Kingdom1 site
Southampton University Hospital Division of Clinical Neurosciences
Southampton, SO16 6YD
About this study
Official title: An Exploratory Phase 2 a Study to Assess Safety, Tolerability, Pharmacodynamic and Pharmacokinetics of VAS203 in Patients With Moderate and Severe Traumatic Brain Injury
In the exploratory multi-center Phase 2 a study safety, tolerability, pharmacodynamics and pharmacokinetics of the Nitric Oxide Synthase inhibitor VAS203 is assessed in patients with moderate and severe traumatic brain injury. Traumatic brain injury patients (32 males) receive 15, 20 and 30 mg/kg VAS203, respectively, by continuous infusion in three cohorts (Cohort 1 open; Cohorts 2 and 3 double blind, randomised placebo-controlled). End of Study for all patients will be Day 14; adverse events and concomitant medications will be documented throughout the study.
Objectives are to assess safety and tolerability of VAS203, to evaluate concentrations of metabolites of VAS203 in plasma and microdialysate and to assess pharmacodynamic effects of VAS203 on surrogate parameters. Safety parameter will include vital signs (blood pressure heart rate, respiration rate, oxygen saturation and blood gases), fluid balance, ECG, laboratory examinations (clinical chemistry, liver function, haematology/coagulation, urinalysis, renal parameters) and adverse events. Concentration of VAS203 will be determined in plasma and microdialysate. Pharmacodynamic parameters will include intracranial pressure (ICP), biochemical parameters in microdialysate (nitrite/nitrate, arginine, citrulline, pyruvate, lactate, glucose), Partial Oxygen Pressure in brain parenchyma and Therapy Intensity Level (TIL).
Read the detailed description
Intravenous administration of study medication for each patient will start as soon as possible but not later than 12 hours after trauma. Patients in Group 1 will receive open label study drug (VAS203). Patients in Group 2 and 3 will be randomised to treatment with VAS203 or placebo.
In addition to study treatment, each patient will receive the best "standard of care" for the study centre; no treatment will be withheld.
- 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
i.v. infusion
SalineDrug
Also called 0.9 % NaCl
i.v. infusion
| Study group | Role | What they receive |
|---|---|---|
| VAS203 15 mg/kg | Experimental | Three 5 mg/kg/12-hours infusion with 12 hours break after each infusion. Total dose: 15 mg/kg Receives: Drug: VAS203 |
| VAS203 20 mg/kg | Experimental | 10 mg/kg/24 hours, 48 hour continuous infusion. Total dose: 20 mg/kg Receives: Drug: VAS203 |
| VAS203 30 mg/kg | Experimental | 10 mg/kg/24 hours, 72 hour continuous infusion. Total dose: 30 mg/kg Receives: Drug: VAS203 |
| Saline | Placebo comparator | 0.9 % Sodium chloride infusion Receives: Drug: Saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and Tolerability of VAS203 in Patients With Moderate and Severe TBI
Tolerability (good, satisfactory, sufficient, poor) of VAS203 in patients with moderate and severe TBI, as judged by the investigators at day 14.
Safety outcome measure description see safety section
Measured: 14 days
Secondary outcomes (3)
Duration (Number of Time-points) of Intracranial Pressure (ICP) > 20 mmHg
Measured: Hourly from start of infusion to 144 hours
Duration (Number of Hours) of Cerebral Perfusion Pressure (CPP) < 60 mmHg
Duration (number of hours) of cerebral perfusion pressure (CPP) < 60 mmHg calculated from ICP and mean arterial blood pressure (MAP): CPP = MAP - ICP)
Measured: Hourly from start of infusion to 144 hours
Therapy Intensity Level Score
Therapy Intensity Level Score: Total Score calculated daily as the sum of all individual measures, range from 3 (good outcome) to 50 (worst outcome):
Scores:
0-2 Head elevation 0-8 Sedation 0-1 Paralysis 1-3 Hyperventilation 0-2 Increased Oxygenation 1-3 Cooling 0-2 Osmotherapy 0-3 CSF Drainage 0-1 Red Blood Cell Transfusion 1-3 Cerebral perfusion pressure 0-1 Surgery for mass lesion 0/5/10 none/unilateral/bilateral Decompressive Craniectomy 0/10 Laparatomy to treat intracranial hypertension due to abdominal hypertension
Measured: Daily from day 1 to day 6
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Dec 2013 (estimated)
- Study startNov 2009
- Primary completionJun 2012
- Study completionSep 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- veriNOS operations GmbH
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Frank Tegtmeier, Dr., Study director, veriNOS operations GmbH
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02012582
- Sponsor's protocol ID
- VAS203/II/1/03
- Acronym
- NOSTRA
- Status last verified
- Feb 2016
- First submitted
- 10 Dec 2013
- Last updated
- 7 Mar 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
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
Study at a glance
From the registry record, last updated by the sponsor on 7 Mar 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Exploratory Phase 2 a Study to Assess Safety, Tolerability, Pharmacodynamic and Pharmacokinetics of VAS203 in Patients With Moderate and Severe Traumatic Brain Injury
- ClinicalTrials.gov ID
- NCT02012582
- Acronym / sponsor ID
- NOSTRA / VAS203/II/1/03
- Conditions
- Traumatic Brain Injury
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- veriNOS operations GmbHIndustry (pharma, biotech, devices)
- Study start
- Nov 2009
- Primary completion
- Jun 2012 (actual)
- Study completion
- Sep 2012 (actual)
- First posted
- 16 Dec 2013 (estimated)
- Results
- Posted 7 Mar 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
In the exploratory multi-center Phase 2 a study safety, tolerability, pharmacodynamics and pharmacokinetics of the Nitric Oxide Synthase inhibitor VAS203 is assessed in patients with moderate and severe traumatic brain injury. Traumatic brain injury patients (32 males) receive 15, 20 and 30 mg/kg VAS203, respectively, by continuous infusion in three cohorts (Cohort 1 open; Cohorts 2 and 3 double blind, randomised placebo-controlled). End of Study for all patients will be Day 14; adverse events and concomitant medications will be documented throughout the study.
Objectives are to assess safety and tolerability of VAS203, to evaluate concentrations of metabolites of VAS203 in plasma and microdialysate and to assess pharmacodynamic effects of VAS203 on surrogate parameters. Safety parameter will include vital signs (blood pressure heart rate, respiration rate, oxygen saturation and blood gases), fluid balance, ECG, laboratory examinations (clinical chemistry, liver function, haematology/coagulation, urinalysis, renal parameters) and adverse events. Concentration of VAS203 will be determined in plasma and microdialysate. Pharmacodynamic parameters will include intracranial pressure (ICP), biochemical parameters in microdialysate (nitrite/nitrate, arginine, citrulline, pyruvate, lactate, glucose), Partial Oxygen Pressure in brain parenchyma and Therapy Intensity Level (TIL).
Detailed description
Intravenous administration of study medication for each patient will start as soon as possible but not later than 12 hours after trauma. Patients in Group 1 will receive open label study drug (VAS203). Patients in Group 2 and 3 will be randomised to treatment with VAS203 or placebo.
In addition to study treatment, each patient will receive the best "standard of care" for the study centre; no treatment will be withheld.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| VAS203 15 mg/kg | Experimental | Drug: VAS203Three 5 mg/kg/12-hours infusion with 12 hours break after each infusion. Total dose: 15 mg/kg |
| VAS203 20 mg/kg | Experimental | Drug: VAS20310 mg/kg/24 hours, 48 hour continuous infusion. Total dose: 20 mg/kg |
| VAS203 30 mg/kg | Experimental | Drug: VAS20310 mg/kg/24 hours, 72 hour continuous infusion. Total dose: 30 mg/kg |
| Saline | Placebo comparator | Drug: Saline0.9 % Sodium chloride infusion |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Written informed consent from patient's legal guardian or legal representative
- 18 - 65 years of age, inclusive
- Head trauma within the last 12 hours
- Traumatic brain injury with Glasgow Coma Score (GCS) ≥ 5 and that requires ICP monitoring
- Catheter placement for monitoring and management of increased ICP
Key exclusion criteria (18 listed)
- Penetrating head injury (e.g. missile, stab wound)
- Not expected to survive more than 24 hours after admission
- Concurrent, but not pre-existing, spinal cord injury
- Unilateral and bilateral fixed and dilated pupil (> 4 mm)
- Cardiopulmonary resuscitation performed post injury
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: Ronopterini.v. infusion | Drug | VAS203 15 mg/kg, VAS203 20 mg/kg, VAS203 30 mg/kg |
| SalineAlso: 0.9 % NaCli.v. infusion | Drug | Saline |
Primary outcome
Safety and Tolerability of VAS203 in Patients With Moderate and Severe TBI
Time frame: 14 days
Tolerability (good, satisfactory, sufficient, poor) of VAS203 in patients with moderate and severe TBI, as judged by the investigators at day 14. Safety outcome measure description see safety section
3 secondary outcomes
Duration (Number of Time-points) of Intracranial Pressure (ICP) > 20 mmHg
Time frame: Hourly from start of infusion to 144 hours
Duration (Number of Hours) of Cerebral Perfusion Pressure (CPP) < 60 mmHg
Time frame: Hourly from start of infusion to 144 hours
Therapy Intensity Level Score
Time frame: Daily from day 1 to day 6
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Mar 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: 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.
- Individual participant dataSharing planned: No
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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.
Frank Tegtmeier, Dr. study director
veriNOS operations GmbH
6 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing VAS203 and Saline in people with Traumatic Brain Injury, run by veriNOS operations GmbH at 6 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 7 Mar 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in Spain, Austria, France, Switzerland, United Kingdom. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 7 Mar 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Safety and Tolerability of VAS203 in Patients With Moderate and Severe TBI (time frame: 14 days). 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 NCT02012582, which also lists 1 linked publication.
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 7 Mar 2016.