The Albumin in Subarachnoid Hemorrhage (ALISAH) multicenter pilot clinical trial: safety and neurologic outcomes.
The Albumin in Subarachnoid Hemorrhage (ALISAH) multicenter pilot clinical trial: safety and neurologic outcomes.
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DOI：
10.1161/strokeaha.111.633958
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发表时间：
2012-03
期刊：
影响因子：
8.3
通讯作者：
ALISAH Investigators
中科院分区：
文献类型：
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作者：
Suarez JI;Martin RH;Calvillo E;Dillon C;Bershad EM;Macdonald RL;Wong J;Harbaugh R;ALISAH Investigators
人血白蛋白已被证明在脑缺血动物模型和患有各种颅内病变的人中发挥神经保护作用。我们研究了25%人血白蛋白（ALB）在蛛网膜下腔出血（SAH）患者中的安全性和耐受性。ALISAH（白蛋白用于蛛网膜下腔出血）初步临床试验是一项开放标签、剂量递增研究。我们打算研究4种不同剂量的ALB，剂量递增（0.625 g/kg：第1级; 1.25 g/kg：第2级; 1.875 g/kg：第3级; 2.5 g/kg：第4级）。每个剂量将给予20名成人患者。每天给药，持续7天。我们根据严重至危及生命的心力衰竭和过敏反应的发生率以及3个月时的功能结局研究了ALB的最大耐受剂量。我们治疗了47名成人受试者：1级20名; 2级20名; 3级7名。我们发现，剂量范围高达1.25 g/kg/天× 7天的患者耐受性良好，无重大剂量限制性并发症。我们还发现，与第1级（OR：3.0513; CI：0.6586 - 14.1367）和国际动脉瘤手术术中低温试验队列（OR：3.1462; CI：0.9158 - 10.8089）相比，第2级入组的受试者的结局趋向于更好的缓解。SAH患者耐受ALB剂量范围高达1.25 g/Kg/天× 7天，无严重并发症，可能具有神经保护作用。基于这些结果，正在计划ALISAH II，这是一项III期，随机，安慰剂对照试验，旨在测试ALB的疗效。临床试验注册信息：NCT 00283400（clinicaltrials.gov）http://clinicaltrials.gov/ct2/show/NCT00283400? term=蛛网膜下腔+出血+houston&rank=1
Human albumin has been shown to exert neuroprotective effects in animal models of cerebral ischemia and humans with various intracranial pathologies. We investigated the safety and tolerability of 25% human albumin (ALB) in patients with subarachnoid hemorrhage (SAH). The ALISAH (Albumin in Subarachnoid Hemorrhage) Pilot Clinical Trial was an open-label, dose-escalation study. We intended to study 4 different dosages of ALB of increasing magnitude (0.625 g/kg: tier 1; 1.25 g/kg: tier 2; 1.875 g/kg: tier 3; and 2.5 g/kg: tier 4). Each dosage was to be given to 20 adult patients. Treatment was administered daily for 7 days. We investigated the maximum tolerated dose of ALB based on the rate of severe-to-life-threatening heart failure and anaphylactic reaction, and functional outcome at 3 months. We treated 47 adult subjects: 20 in tier 1; 20 in tier 2; and 7 in tier 3. We found that doses ranging up to 1.25 g/kg/day × 7 days were tolerated by patients without major dose-limiting complications. We also found that outcomes trended towards better responses in those subjects enrolled in tier 2 compared to tier 1 (OR: 3.0513; CI: 0.6586 – 14.1367) and to the International Intra-operative Hypothermia for Aneurysm Surgery Trial cohort (OR: 3.1462; CI: 0.9158 – 10.8089). ALB in doses ranging up to 1.25 g/Kg/day × 7 days was tolerated by patients with SAH without major complications and may be neuroprotective. Based on these results, planning of the ALISAH II, a Phase III, randomized, placebo-controlled trial to test the efficacy of ALB is underway. Clinical Trial Registration Information: NCT00283400 (clinicaltrials.gov) http://clinicaltrials.gov/ct2/show/NCT00283400?term=subarachnoid+hemorrhage+houston&rank=1