ProTECT III

项目摘要/摘要 创伤性脑损伤是世界范围内过早死亡和致残的主要原因。没有任何治疗方法 在降低死亡率和改善功能结果方面有效。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，检查药代动力学， 孕酮的安全性和活性，这是一种类固醇，被发现在多种疾病中具有强大的神经保护特性 不同的脑损伤动物模型。基于广泛的临床前活动证据和 我们的初步研究结果令人振奋，我们建议进行第三阶段临床试验，以明确评估 本疗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孕酮(在4小时内开始)的效果 受伤时间为72小时，然后再减少24小时)与安慰剂相比 治疗中重度(GCS 12-4)脑外伤患者。 我们的次要目标是检查黄体酮与安慰剂对中度到中度癌症患者的影响。 重型颅脑损伤后6个月死亡率、残疾评定量表评分、认知、神经和功能结果 使用选定的一组测试，以及不良事件和严重不良事件的发生率。 如果在动物和我们的先导研究中观察到的治疗益处是重复的，那么给药 静脉注射黄体酮可以降低死亡率，改善神经功能。积极的结果将 代表着脑外伤治疗方面的重大进步。

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.