Treatment of Subarachnoid Hemorrhage with Human Albumin

描述（由申请方提供）：拟定研究将评价25%人血白蛋白（HA）治疗蛛网膜下腔出血（SAH）患者的耐受性和安全性。据估计，美国每年有37，500人患有SAH。SAH与51%的死亡率相关，三分之一的幸存者在功能上依赖。脑血管痉挛（CV）已被确定为神经功能恶化的最重要原因。CV可能是由于多种分子机制。使用具有各种作用的神经保护剂，如HA，对于预防CV和改善SAH患者的临床结局非常重要。拟议的开放标签、剂量递增研究将通过为确定性III期临床试验提供关于HA治疗SAH患者疗效的必要信息，对公共卫生产生重要影响。本研究将入组最多80例符合合格性标准的SAH患者。将评价每天给予4个剂量的HA（0.625、1.25、1.875和2.5 g/kg），持续7天。将在第一组20例受试者中评价最低剂量。根据既往研究的数据定义了特定的安全性阈值。数据和安全性监查委员会将根据充血性心力衰竭（CHF）发生率的评价，批准或不批准推进至下一个更高的HA剂量。该研究将评估三个结果：HA剂量的安全性和耐受性以及功能结果。主要耐受性结局将定义为受试者接受全部分配剂量HA而不发生需要终止治疗的明显CHF的能力。次要结局将是严重不良事件（包括神经系统和医学并发症以及过敏反应）。神经系统并发症包括治疗后CV、再出血、脑积水和癫痫发作的发生率。通过格拉斯哥结局量表、Barthel指数、改良兰金量表、NIH卒中量表和卒中影响量表测定3个月功能结局，以初步估计HA的治疗效果。这项研究的时间轴为三年。

DESCRIPTION (provided by applicant): The proposed study will evaluate the tolerability and safety of 25% human albumin (HA) therapy in patients with subarachnoid hemorrhage (SAH). It is estimated that 37,500 people in the USA have SAH every year. SAH is associated with a 51% mortality rate and one third of survivors are left functionally dependent. Cerebral vasospasm (CV) has been identified as the most important reason for neurological deterioration. CV may be due to multiple molecular mechanisms. The use of a neuroprotective agent with various actions, like HA, would be important for prevention of CV and improved clinical outcome in patients with SAH. The proposed open-label, dose-escalation study will have important public health implications by providing necessary information for a definitive phase III clinical trial regarding the efficacy of treatment with HA in patients with SAH. The study will enroll a maximum of 80 patients with SAH who meet the eligibility criteria. Four dosages of HA (0.625, 1.25, 1.875, and 2.5 g/kg) administered daily for seven days will be evaluated. The lowest dosage will be evaluated in the first group of 20 subjects. A specific safety threshold has been defined based on data from previous studies. The Data and Safety Monitoring Board will approve or disapprove advancing to the next higher HA dosage based on the evaluation of the rate of congestive heart failure (CHF). The study will assess three outcomes: safety and tolerability of the HA dosages and the functional outcome. The primary tolerability outcome will be defined as the subject's ability to receive the full allocated dose of HA without incurring frank CHF that requires termination of treatment. Secondary outcomes will be serious adverse events (including neurological and medical complications, and anaphylactic reactions). Neurological complications comprise incidence of CV, rebleeding, hydrocephalus, and seizures after treatment. The three-month functional outcome determined',by Glasgow Outcome Scale, Barthel Index, modified Rankin Scale, NIH Stroke Scale and Stroke Impact Scale will be; measured to obtain a preliminary estimate of the treatment effect of HA. The timeline of the study is three years.