Treatment of Subarachnoid Hemorrhage with Human Albumin

人白蛋白治疗蛛网膜下腔出血

• 批准号: 7048736
• 负责人: JOSE I SUAREZ
• 金额: $ 52.24万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-02-01 至 2007-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7048736
• 关键词: albumins; blood pressure; brain disorder chemotherapy; cerebral ischemia /hypoxia; clinical research; clinical trials; congestive heart failure; dosage; drug administration rate /duration; drug screening /evaluation; heart rate; human subject; human therapy evaluation; medical complication; neurologic manifestations; patient oriented research; serum albumin; stroke therapy; subarachnoid hemorrhage; vasospasm

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.

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可能是由多种分子机制引起的。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、剂量递增研究将为关于 HA 对 SAH 患者疗效的明确 III 期临床试验提供必要的信息，从而具有重要的公共健康意义。该研究将招募最多 80 名符合资格标准的 SAH 患者。将评估每天施用的四种剂量的 HA（0.625、1.25、1.875 和 2.5 g/kg），持续 7 天。最低剂量将在第一组 20 名受试者中进行评估。根据先前研究的数据定义了特定的安全阈值。数据和安全监测委员会将根据充血性心力衰竭 (CHF) 发生率的评估，批准或不批准推进到下一个更高的 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。主要耐受性结果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明显CHF的能力。次要结局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治疗后心血管、再出血、脑积水和癫痫发作的发生率。由格拉斯哥结果量表、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果将是：测量以获得HA治疗效果的初步估计。该研究的期限为三年。