ProTECT III

项目摘要/总结 创伤性脑损伤（TBI）是世界范围内过早死亡和残疾的主要原因。没有任何治疗 有效降低死亡率和改善功能结局。我们最近完成了一个由NINDS资助的， I/IIa期双盲、随机安慰剂对照初步临床试验，检查药代动力学， 安全性和活性的孕酮，类固醇发现有强大的神经保护特性，在多个 不同的脑损伤动物模型。基于广泛的临床前活性证据和 我们的试点研究有希望的结果，我们建议进行III期临床试验，以明确评估 这种治疗对患有中度至重度急性TBI的成人的有效性。 我们的主要目的是确定静脉注射黄体酮（在4小时内开始）的效果。 小时的损伤，给药72小时，然后再进行24小时的逐渐减量）与安慰剂相比， 治疗中度至重度（GCS 12-4）创伤性脑损伤的患者。 我们的次要目的是检查孕酮与安慰剂在中度至重度子宫内膜异位症患者中的作用。 重度TBI 6个月死亡率、残疾评定量表评分、认知、神经和功能结局 使用一组精选的测试，以及不良和严重不良事件的发生率。 如果在动物中观察到的和从我们的初步研究中观察到的治疗益处被复制， 静脉注射黄体酮可以降低死亡率并改善神经功能。积极的结果将 代表了TBI治疗的重大进展。

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.