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.
Frank Tegtmeier  1 ,  Reinhard Schinzel  2 ,  Ronny Beer  3 ,  Diederik Bulters  4 ,  Jean-Yves LeFrant  5 ,  Joan Sahuquillo  6 ,  Andreas Unterberg  7 ,  Peter Andrews  8 ,  Antonio Belli  9 ,  Javier Ibanez  10 ,  Alfonso Lagares  11 ,  Michael Mokry  12 ,  Harald Willschke  13 ,  Charlotte Flüh  14 ,  Erich Schmutzhard  3 ,  NOSTRA Investigators
Affiliations
  • 1. vasopharm GmbH, Würzburg, Germany.
  • 2. vasopharm GmbH, Würzburg, Germany. [email protected].
  • 3. Medizinische Universität Innsbruck, Innsbruck, Austria.
  • 4. Wessex Neurological Centre University Hospital, Southampton, UK.
  • 5. Hopital Universitaire Caremeau , Nimes, France.
  • 6. Vall d'Hebron University Hospital , Barcelona, Spain.
  • 7. Universitätsklinikum Heidelberg, Heidelberg, Germany.
  • 8. Western General Hospital Lothian University , Edinburgh, UK.
  • 9. Queen Elizabeth Hospital, Birmingham, UK.
  • 10. Espases University Hospital , Palma de Mallorca, Spain.
  • 11. Hospital Universitario 12 de Octubre , Madrid, Spain.
  • 12. LKH - Universitätsklinikum Graz, Graz, Austria.
  • 13. Medizinische Universität Wien, Wien, Austria.
  • 14. Universitätsklinikum Schleswig-Holstein, Kiel, Germany.
PMID: 31937347 DOI: 10.1186/s13063-019-3965-4
Abstract

Background: Traumatic brain injury is a leading cause of death and disability worldwide. The nitric oxide synthase inhibitor Ronopterin was shown to improve clinical outcome by enhancing neuroprotection in a phase IIa trial.

Methods/design: The NOSTRA phase III trial (Ronopterin in traumatic brain injury) is a multi-centre, prospective, randomised, double-blinded, placebo-controlled, phase III trial in Europe. It aims at determining whether the administration of Ronopterin compared to placebo improves neurological outcome in patients with moderate or severe traumatic brain injury at 6 months after injury. The trial is designed to recruit patients between 18 and 60 years of age with moderate or severe traumatic brain injury (Glasgow Coma Scale score ≥ 3) and requiring insertion of an intracranial pressure probe. Trial patients will receive a 48-h intravenous infusion of either Ronopterin or placebo starting at the earliest 6 h and at the latest 18 h after injury. The primary outcome will be the extended Glasgow Outcome Score (eGOS) at 6 months. Secondary outcomes will include the Quality of Life Index (QOLIBRI) at 6 months after the injury and the eGOS at 3 months after the injury. Additionally, effects on mortality, intracranial pressure and cerebral perfusion pressure are evaluated.

Discussion: The trial aims to provide evidence on the efficacy and safety of Ronopterin in patients with traumatic brain injury.

Trial registration: EudraCT, 2013-003368-29. Registered on 9 March 2016. ClinicalTrials.gov, NCT02794168. Registered on 8 June 2016. Protocol version 14.0 from 05 November 2018.

Keywords
Nitric oxide synthase inhibition; Outcome; Randomised controlled trials; Traumatic brain injury.
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