Treatment of Subarachnoid Hemorrhage with Human Albumin

描述（由申请人提供）：拟议的研究将评估25%人白蛋白（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可能由多种分子机制引起。使用具有多种作用的神经保护剂，如HA，对于预防CV和改善SAH患者的临床结果非常重要。拟议的开放标签、剂量递增研究将对公共卫生产生重要影响，为确定HA治疗SAH患者疗效的III期临床试验提供必要信息。该研究将招募最多80名符合资格标准的SAH患者。评估每日给药剂量（0.625、1.25、1.875和2.5 g/kg），连续7天。在第一组20名受试者中评估最低剂量。一个特定的安全阈值是根据先前研究的数据确定的。数据和安全监测委员会将根据充血性心力衰竭（CHF）的评估批准或不批准下一个更高的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。主要耐受性指标将被定义为受试者接受全部分配剂量的HA而不发生需要终止治疗的直接CHF的能力。次要结果将是严重的不良事件（包括神经和医学并发症，以及过敏反应）。神经系统并发症包括CV、再出血、脑积水和治疗后癫痫发作的发生率。由格拉斯哥结局量表、Barthel指数、改良Rankin量表、NIH卒中量表和卒中影响量表确定的三个月功能结局为；测量，以获得对HA处理效果的初步估计。这项研究的时间是三年。

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.