ProTECT III

保护III

• 批准号: 8323400
• 负责人: DAVID W WRIGHT
• 金额: $ 638.62万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-01 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8323400
• 关键词: Acute; Adult; Age; American; Animal Model; Animals; Brain Injuries; Cessation of life; Clinical Trials; Cognitive; Data; Double-Blind Method; Drug Kinetics; Economics; Funding; Glasgow Coma Scale; Glasgow Outcome Scale; Hospitalization; Hour; Human; Injury; Injury Severity Score; Intravenous; Measures; Methodology; National Institute of Neurological Disorders and Stroke; Nervous System Physiology; Neurological outcome; Outcome; Patients; Phase; Phase III Clinical Trials; Pilot Projects; Placebo Control; Placebos; Progesterone; Property; Publishing; Randomized; Recovery; Safety; Serious Adverse Event; Severe Adverse Event; Severities; Steroids; Testing; Therapeutic; Traumatic Brain Injury; Treatment Efficacy; base; clinical research site; disability; functional outcomes; improved; intravenous administration; mortality; pre-clinical; premature; primary outcome; sex

PROJECT ABSTRACT / SUMMARY Traumatic brain injury (TBI) is a major cause of premature death and disability worldwide. No therapy has been effective in reducing mortality and improving functional outcomes. We recently completed an NINDS-funded, Phase I/IIa double-blinded, randomized placebo-controlled pilot clinical trial examining the pharmacokinetics, safety, and activity of progesterone, a steroid found to have powerful neuroprotective properties in multiple different animal models of brain injury. Based on the extensive preclinical evidence of activity and the promising findings of our pilot study we propose to conduct a phase III clinical trial to definitively assess the efficacy of this treatment for adults with moderate to severe acute TBI. Our primary objective is to determine the effect of administering intravenous progesterone (initiated within 4 hours of injury and administered for 72 hours, followed by an additional 24 hour taper) versus placebo for treating victims of moderate to severe (GCS 12-4) TBI. Our secondary objectives are to examine the effects of progesterone vs. placebo in patients with moderate to severe TBI on 6 month mortality, Disability Rating Scale score, cognitive, neurological and functional outcome using a select battery of tests, and the rates of adverse and severe adverse events. If the therapeutic benefits observed in animals and from our pilot study are replicated, administration of intravenous progesterone should decrease mortality and improve neurological function. Positive results would represent a major advance in the treatment of TBI.

项目摘要 /摘要 创伤性脑损伤（TBI）是全球过早死亡和残疾的主要原因。没有治疗 有效降低死亡率并改善功能结果。我们最近完成了Ninds资助的 I/IIA阶段双盲，随机安慰剂对照的试验临床试验检查药代动力学， 孕酮的安全性和活性是一种类固醇，发现多种具有强大的神经保护特性 脑损伤的不同动物模型。基于活动的广泛临床前证据和 我们的试点研究的有希望的发现，我们建议进行III期临床试验，以确定评估 这种治疗对中度至重度急性TBI的成年人的疗效。 我们的主要目的是确定施用静脉孕酮的作用（在4中启动 小时受伤并进行72小时，然后再进行24小时锥度）与安慰剂相比 治疗中度至重度（GCS 12-4）TBI的受害者。 我们的次要目标是检查孕酮与安慰剂在中度至中等患者中的影响 严重的TBI在6个月死亡率，残疾评级评分，认知，神经和功能结果 使用精选的测试，以及不利和严重不良事件的速度。 如果复制动物和试点研究中观察到的治疗益处，则 静脉孕酮应降低死亡率并改善神经功能。积极的结果将是 代表了TBI治疗的重大进步。