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

• Published in: Current controlled trials in cardiovascular medicine Vol. 21; no. 1; pp. 80 - 9
• Main Authors: Tegtmeier, Frank, Schinzel, Reinhard, Beer, Ronny, Bulters, Diederik, LeFrant, Jean-Yves, Sahuquillo, Joan, Unterberg, Andreas, Andrews, Peter, Belli, Antonio, Ibanez, Javier, Lagares, Alfonso, Mokry, Michael, Willschke, Harald, Flüh, Charlotte, Schmutzhard, Erich
• Format: Journal Article
• Language: English
• Published: London BioMed Central 14.01.2020; BMC
• Subjects: Adolescent; Adult; Age; Biomedicine; Biopterin; Biopterins - administration & dosage; Biopterins - adverse effects; Biopterins - analogs & derivatives; Biopterins - therapeutic use; Brain Injuries, Traumatic; Brain Injuries, Traumatic - drug therapy; Brain Injuries, Traumatic - mortality; Brain Injuries, Traumatic - psychology; Brain research; Case-Control Studies; Catheters; Cognitive science; Coma; Consent; Creatinine; Double-Blind Method; Double-blind studies; Drug dosages; Drug overdose; Europe; Europe - epidemiology; Glasgow Coma Scale; Head injuries; Health Sciences; Humans; Infusions, Intravenous; Infusions, Intravenous - methods; Medicine; Medicine & Public Health; Middle Aged; Neuroscience; Nitric oxide; Nitric Oxide Synthase; Nitric Oxide Synthase - antagonists & inhibitors; Nitric oxide synthase inhibition; Outcome; Patients; Pharmacy; Placebos; Placebos - administration & dosage; Prospective Studies; Quality of Life; Randomised controlled trials; Statistics for Life Sciences; Study Protocol; Substance abuse treatment; Traumatic brain injury; Treatment Outcome; Young Adult; Europe; Traumatic brain injury; Nitric oxide synthase inhibition; Randomised controlled trials; Outcome
• ISSN: 1745-6215; 1745-6215
• DOI: 10.1186/s13063-019-3965-4

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.