ProTECT II: Progesterone for TBI, MCCT Planning Grant

描述（由申请人提供）： 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。可能的功能结果。我们最近完成了一项NINDS资助的I/IIa期双盲随机安慰剂对照试点临床试验，研究了黄体酮的药代动力学，安全性和活性，黄体酮是一种类固醇，在多种不同的脑损伤动物模型中具有强大的神经保护作用。基于令人鼓舞的结果，我们建议进行III期临床试验，以确定这种治疗在中度至重度TBI成人中的疗效和安全性。 我们的主要目的是确定在损伤后4小时内开始静脉注射黄体酮，持续72小时，然后再增加24小时的减量，与安慰剂相比，在改善中重度创伤性脑损伤患者的功能结局方面的有效性。主要功能结果将通过在损伤后6个月测量的格拉斯哥结果量表-增强（GOSE）确定。次要目的是检查孕酮与安慰剂对死亡率、颅内压、功能性神经结局的替代指标、不良事件发生率的影响，并检查中重度TBI患者5个临床亚组的有效性。为了继续进行III期临床试验，我们正在提交临床试验计划补助金。规划补助金的具体目标是完成操作手册;确定、招募和认证参与中心;评估每个候选中心招募合格患者的能力;制定MCCT数据管理计划;完成研究材料并生成研究表格;准备培训时间表和材料;建立委员会和组织结构图;编制预算和合作协议：制定IRB方案范本，与当地IRB合作实施知情同意例外;并获得FDA IND最终批准，静脉使用黄体酮治疗急性脑损伤成人，但需知情同意例外。

DESCRIPTION (provided by applicant): Traumatic brain injury (TBI) is a major cause of premature death and disability worldwide. With the possible functional outcomes. We recently completed an NINDS-funded, Phase l/lla 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 encouraging results, we propose to conduct a phase III clinical trial to determine the efficacy and confirm safety of this treatment in adults with moderate to severe TBI. Our primary objective is to determine the effectiveness of intravenous progesterone initiated within 4 hours of injury and administered for 72 hours, followed by an additional 24 hour taper, as compared to placebo at improving functional outcome in patients with moderate to severe traumatic brain injury. The primary functional outcome will be determined by Glasgow Outcome Scale - Enhanced (GOSE) measured at 6 months after injury. Secondary objectives are to examine the effects of progesterone versus placebo on mortality, intracranial pressure, alternative measures of functional neurological outcome, on rates of adverse events, and examine the effectiveness in 5 clinical subgroups in patients with moderate to severe TBI. In order to proceed towards the Phase III clinical trial, we are submitting a clinical trial planning grant. The specific objectives of the planning grant are to complete a Manual of Operations; identify, recruit and certify participating centers; assess each candidate center's ability to enroll eligible patients; develop a MCCT data management plan; complete study materials and generate study forms; prepare training schedules and materials; establish committees and organizational chart; prepare budgets and cooperative agreements: develop a model IRB protocol, work with local IRBs to implement Exception from Consent; and obtain FDA IND final approval for intravenous use of progesterone to treat acutely brain-injured adults with an Exception from Informed Consent.