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.

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.

• Authors: Frank Tegtmeier, Reinhard Schinzel, Ronny Beer, Diederik Bulters, Jean-Yves LeFrant, Joan Sahuquillo, Andreas Unterberg, Peter Andrews, Antonio Belli, Javier Ibanez, Alfonso Lagares, Michael Mokry, Harald Willschke, Charlotte Flüh, Erich Schmutzhard, NOSTRA Investigators
• Journal: Trials (Trials) Vol. 21 Issue 1 Pg. 80 (Jan 14 2020) ISSN: 1745-6215 [Electronic] England
• PMID: 31937347 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial)

Chemical References

• Placebos
• 4-amino-tetrahydrobiopterin
• Biopterin
• Nitric Oxide Synthase

Topics

• Adolescent
• Adult
• Biopterin (administration & dosage, adverse effects, analogs & derivatives, therapeutic use)
• Brain Injuries, Traumatic (drug therapy, mortality, psychology)
• Case-Control Studies
• Double-Blind Method
• Europe (epidemiology)
• Glasgow Coma Scale
• Humans
• Infusions, Intravenous (methods)
• Middle Aged
• Nitric Oxide Synthase (antagonists & inhibitors)
• Placebos (administration & dosage)
• Prospective Studies
• Quality of Life
• Treatment Outcome
• Young Adult