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.

中文翻译：

---

Ronopterin (VAS203) 对中度和重度创伤性脑损伤患者的疗效（NOSTRA III 期试验）：一项验证性、安慰剂对照、随机、双盲、多中心研究的研究方案。


背景技术创伤性脑损伤是全世界死亡和残疾的主要原因。在 IIa 期试验中，一氧化氮合酶抑制剂 Ronopterin 被证明可以通过增强神经保护来改善临床结果。方法/设计 NOSTRA III 期试验（罗硝蝶呤治疗创伤性脑损伤）是在欧洲进行的一项多中心、前瞻性、随机、双盲、安慰剂对照 III 期试验。其目的是确定与安慰剂相比，给予 Ronopterin 是否可以改善中度或重度创伤性脑损伤患者在受伤后 6 个月的神经学结果。该试验旨在招募年龄在18至60岁之间、患有中度或重度创伤性脑损伤（格拉斯哥昏迷量表评分≥3）且需要插入颅内压探头的患者。试验患者将在受伤后最早 6 小时和最晚 18 小时开始接受 48 小时静脉输注 Ronopterin 或安慰剂。主要结果将是 6 个月时的扩展格拉斯哥结果评分 (eGOS)。次要结果包括受伤后 6 个月的生活质量指数 (QOLIBRI) 和受伤后 3 个月的 eGOS。此外，还评估了对死亡率、颅内压和脑灌注压的影响。讨论 该试验旨在提供罗硝蝶呤治疗脑外伤患者的有效性和安全性的证据。试用注册 EudraCT，2013-003368-29。于 2016 年 3 月 9 日注册。ClinicalTrials.gov，NCT02794168。注册于 2016 年 6 月 8 日。协议版本 14.0 自 2018 年 11 月 5 日起。