Treatment of Subarachnoid Hemorrhage with Human Albumin

描述(申请人提供)：这项拟议的研究将评估25%人血清白蛋白(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37500人患有SAH。SAH与51%的死亡率有关，三分之一的幸存者仍有功能依赖。脑血管痉挛(CV)已被认为是神经功能恶化的最重要原因。血管紧张素转换酶可能与多种分子机制有关。使用一种具有多种作用的神经保护剂，如HA，对于预防脑血管意外和改善SAH患者的临床结果将是重要的。拟议的开放标签、剂量递增研究将为关于HA治疗SAH患者的疗效的最终III期临床试验提供必要的信息，从而对公众健康产生重要影响。这项研究将招募最多80名符合资格标准的SAH患者。将评估四种剂量的HA(0.625、1.25、1.875和2.5g/kg)，连续七天每天给药。最低剂量将在第一组20名受试者中进行评估。根据之前的研究数据，已经定义了一个特定的安全阈值。数据和安全监测委员会将根据充血性心力衰竭(CHF)的比率评估，批准或不批准提前使用下一个更高的HA剂量。这项研究将评估三种结果：HA剂量的安全性和耐受性以及功能结果。主要耐受性结果将被定义为受试者接受全部分配剂量的HA而不会招致需要终止治疗的坦率心力衰竭的能力。次要结果将是严重的不良反应(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治疗后脑血管意外、再出血、脑积水和癫痫发作的发生率。通过格拉斯哥预后评分、Barthel指数、改良Rankin评分、NIH卒中评分和卒中影响评分评定3个月的功能结局，初步评估HA的治疗效果。这项研究的时间表是三年。

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.