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Phase 2 a Study to Assess Safety and Pharmacokinetics of VAS203 in Patients With Traumatic Brain Injury (NOSTRA)

2016年2月8日 更新者:Vasopharm GmbH

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).

研究概览

地位

完全的

详细说明

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.

研究类型

介入性

注册 (实际的)

32

阶段

  • 阶段2

联系人和位置

本节提供了进行研究的人员的详细联系信息,以及有关进行该研究的地点的信息。

学习地点

      • Innsbruck、奥地利、6020
        • Medical University Innsbruck Department of Neurology
      • Toulon、法国、83800
        • HIA Sainte-Anne Boulevard Sainte-Anne
      • Zuerich、瑞士、8091
        • University Hospital Zuerich Surgical Intensive Care
      • Southampton、英国、SO16 6YD
        • Southampton University Hospital Division of Clinical Neurosciences
      • Barcelona、西班牙、08035
        • Vall d'Hebron University Hospital Department of Neurosurgery
      • Barcelona、西班牙、08036
        • Hospital Clinic University of Barcelona Surgical Intensive Care Unit

参与标准

研究人员寻找符合特定描述的人,称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。

资格标准

适合学习的年龄

18年 至 65年 (成人、年长者)

接受健康志愿者

有资格学习的性别

全部

描述

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

学习计划

本节提供研究计划的详细信息,包括研究的设计方式和研究的衡量标准。

研究是如何设计的?

设计细节

  • 主要用途:治疗
  • 分配:随机化
  • 介入模型:并行分配
  • 屏蔽:四人间

武器和干预

参与者组/臂
干预/治疗
实验性的: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
其他名称:
  • 旋风蝶呤
实验性的:VAS203 20 mg/kg
10 mg/kg/24 hours, 48 hour continuous infusion. Total dose: 20 mg/kg
i.v. infusion
其他名称:
  • 旋风蝶呤
实验性的:VAS203 30 mg/kg
10 mg/kg/24 hours, 72 hour continuous infusion. Total dose: 30 mg/kg
i.v. infusion
其他名称:
  • 旋风蝶呤
安慰剂比较:Saline
0.9 % Sodium chloride infusion
i.v. infusion
其他名称:
  • 0.9 % NaCl

研究衡量的是什么?

主要结果指标

结果测量
措施说明
大体时间
Safety and Tolerability of VAS203 in Patients With Moderate and Severe TBI
大体时间: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

次要结果测量

结果测量
措施说明
大体时间
Duration (Number of Time-points) of Intracranial Pressure (ICP) > 20 mmHg
大体时间: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
大体时间: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
大体时间: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

合作者和调查者

在这里您可以找到参与这项研究的人员和组织。

调查人员

  • 研究主任:Frank Tegtmeier, Dr.、Vasopharm GmbH

出版物和有用的链接

负责输入研究信息的人员自愿提供这些出版物。这些可能与研究有关。

研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查,以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始

2009年11月1日

初级完成 (实际的)

2012年6月1日

研究完成 (实际的)

2012年9月1日

研究注册日期

首次提交

2013年12月10日

首先提交符合 QC 标准的

2013年12月13日

首次发布 (估计)

2013年12月16日

研究记录更新

最后更新发布 (估计)

2016年3月7日

上次提交的符合 QC 标准的更新

2016年2月8日

最后验证

2016年2月1日

更多信息

与本研究相关的术语

计划个人参与者数据 (IPD)

计划共享个人参与者数据 (IPD)?

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VAS203的临床试验

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