ProTECT III

外伤性脑损伤（TBI）是世界范围内过早死亡和残疾的主要原因。没有一种治疗方法能有效降低死亡率和改善功能预后。我们最近完成了一项由ninds资助的I/IIa期双盲、随机安慰剂对照的先导临床试验，研究孕酮的药代动力学、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具有强大的神经保护特性。基于广泛的临床前证据和我们的试点研究的有希望的发现，我们建议进行一项III期临床试验，以明确评估该治疗对中度至重度急性TBI成人的疗效。我们的主要目的是确定静脉注射黄体酮（在受伤后4小时内开始，72小时，随后24小时逐渐减少）与安慰剂治疗中重度（GCS 12-4） TBI患者的效果。我们的次要目标是研究黄体酮与安慰剂对中重度TBI患者6个月死亡率、残疾评定量表评分、认知、神经和功能结局的影响，以及不良和严重不良事件的发生率。如果在动物和我们的初步研究中观察到的治疗效果被复制，静脉注射黄体酮应该会降低死亡率并改善神经功能。积极的结果将代表创伤性脑损伤治疗的重大进展。

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.