ProTECT III

保护III

• 批准号: 8113157
• 负责人: DAVID W WRIGHT
• 金额: $ 833.03万
• 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/8113157
• 关键词: ProTECT; III

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.

创伤性脑损伤是世界范围内过早死亡和致残的主要原因。在降低死亡率和改善功能结果方面，没有任何治疗方法是有效的。我们最近完成了一项由NINDS资助的、I/IIa期双盲、随机安慰剂对照的试点临床试验，检查了孕酮的药代动力学、安全性和活性。孕酮是一种类固醇，在多种不同的脑损伤动物模型中被发现具有强大的神经保护特性。基于广泛的临床前活性证据和我们的初步研究的有希望的结果，我们建议进行一项III期临床试验，以明确评估这种治疗方法对成人中重度急性脑外伤的疗效。我们的主要目标是确定静脉注射黄体酮(在受伤后4小时内开始，持续72小时，然后再逐渐减少24小时)与安慰剂治疗中重度(GCS 12-4)脑外伤患者的效果。我们的次要目标是检验黄体酮和安慰剂对中重度脑外伤患者6个月死亡率、残疾评定量表评分、认知、神经和功能结果的影响，以及不良和严重不良事件的发生率。如果在动物身上观察到的治疗效果和我们的初步研究是重复的，静脉注射黄体酮应该会降低死亡率并改善神经功能。阳性结果将代表着脑损伤治疗的重大进步。