- ICH GCP
- Registro degli studi clinici negli Stati Uniti
- Sperimentazione clinica NCT02012582
Phase 2 a Study to Assess Safety and Pharmacokinetics of VAS203 in Patients With Traumatic Brain Injury (NOSTRA)
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).
Panoramica dello studio
Descrizione dettagliata
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.
Tipo di studio
Iscrizione (Effettivo)
Fase
- Fase 2
Contatti e Sedi
Luoghi di studio
-
-
-
Innsbruck, Austria, 6020
- Medical University Innsbruck Department of Neurology
-
-
-
-
-
Toulon, Francia, 83800
- HIA Sainte-Anne Boulevard Sainte-Anne
-
-
-
-
-
Southampton, Regno Unito, SO16 6YD
- Southampton University Hospital Division of Clinical Neurosciences
-
-
-
-
-
Barcelona, Spagna, 08035
- Vall d'Hebron University Hospital Department of Neurosurgery
-
Barcelona, Spagna, 08036
- Hospital Clinic University of Barcelona Surgical Intensive Care Unit
-
-
-
-
-
Zuerich, Svizzera, 8091
- University Hospital Zuerich Surgical Intensive Care
-
-
Criteri di partecipazione
Criteri di ammissibilità
Età idonea allo studio
Accetta volontari sani
Sessi ammissibili allo studio
Descrizione
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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)
- 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
Piano di studio
Come è strutturato lo studio?
Dettagli di progettazione
- Scopo principale: Trattamento
- Assegnazione: Randomizzato
- Modello interventistico: Assegnazione parallela
- Mascheramento: Quadruplicare
Armi e interventi
Gruppo di partecipanti / Arm |
Intervento / Trattamento |
---|---|
Sperimentale: VAS203 15 mg/kg
Three 5 mg/kg/12-hours infusion with 12 hours break after each infusion.
Total dose: 15 mg/kg
|
i.v. infusion
Altri nomi:
|
Sperimentale: VAS203 20 mg/kg
10 mg/kg/24 hours, 48 hour continuous infusion.
Total dose: 20 mg/kg
|
i.v. infusion
Altri nomi:
|
Sperimentale: VAS203 30 mg/kg
10 mg/kg/24 hours, 72 hour continuous infusion.
Total dose: 30 mg/kg
|
i.v. infusion
Altri nomi:
|
Comparatore placebo: Saline
0.9 % Sodium chloride infusion
|
i.v. infusion
Altri nomi:
|
Cosa sta misurando lo studio?
Misure di risultato primarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
---|---|---|
Safety and Tolerability of VAS203 in Patients With Moderate and Severe TBI
Lasso di tempo: 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 |
14 days
|
Misure di risultato secondarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
---|---|---|
Duration (Number of Time-points) of Intracranial Pressure (ICP) > 20 mmHg
Lasso di tempo: Hourly from start of infusion to 144 hours
|
Hourly from start of infusion to 144 hours
|
|
Duration (Number of Hours) of Cerebral Perfusion Pressure (CPP) < 60 mmHg
Lasso di tempo: Hourly from start of infusion to 144 hours
|
Duration (number of hours) of cerebral perfusion pressure (CPP) < 60 mmHg calculated from ICP and mean arterial blood pressure (MAP): CPP = MAP - ICP)
|
Hourly from start of infusion to 144 hours
|
Therapy Intensity Level Score
Lasso di tempo: Daily from day 1 to day 6
|
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 |
Daily from day 1 to day 6
|
Collaboratori e investigatori
Sponsor
Investigatori
- Direttore dello studio: Frank Tegtmeier, Dr., Vasopharm GmbH
Pubblicazioni e link utili
Studiare le date dei record
Studia le date principali
Inizio studio
Completamento primario (Effettivo)
Completamento dello studio (Effettivo)
Date di iscrizione allo studio
Primo inviato
Primo inviato che soddisfa i criteri di controllo qualità
Primo Inserito (Stima)
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Stima)
Ultimo aggiornamento inviato che soddisfa i criteri QC
Ultimo verificato
Maggiori informazioni
Termini relativi a questo studio
Termini MeSH pertinenti aggiuntivi
Altri numeri di identificazione dello studio
- VAS203/II/1/03
Piano per i dati dei singoli partecipanti (IPD)
Hai intenzione di condividere i dati dei singoli partecipanti (IPD)?
Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .
Prove cliniche su Trauma cranico
-
University of PadovaCompletatoPropofol | Anestesia Brain MonitoringItalia
-
University of PadovaCompletato
-
University of PadovaReclutamentoAnestesia Brain MonitoringItalia
-
University of PadovaCompletato
-
University of PadovaCompletato
-
University of PadovaCompletatoLidocaina | Anestesia Brain MonitoringItalia
-
University of PadovaCompletatoPropofol | Anestesia Brain MonitoringItalia
-
University of Dublin, Trinity CollegeSconosciutoBrain Health Atleti d'élite in pensione
-
Hospital Universitari Son DuretaEspen; This research prize was funded by Nestle Nutrition Institute and by Fresenius...CompletatoTrauma da moderato a grave, come definito da an | Injury Severity Score (ISS) > 12 punti sono stati inclusi nello studio.Spagna
-
Assiut UniversityCompletatoMorfometria basata su Brain Voxel in ManiaEgitto
Prove cliniche su VAS203
-
Vasopharm GmbHICON plcCompletatoTrauma cranicoRegno Unito, Spagna, Francia, Austria, Germania
-
Vasopharm GmbHWinicker Norimed GmbHCompletatoCompromissione della funzione renale in volontari saniGermania