Combination of the Immune Modulator Fingolimod With Alteplase in Acute Ischemic Stroke: A Pilot Trial.
Combination of the Immune Modulator Fingolimod With Alteplase in Acute Ischemic Stroke: A Pilot Trial.
复制标题
免疫调节剂芬戈莫德与阿替普酶联合治疗急性缺血性中风：初步试验。
DOI：
10.1161/circulationaha.115.016371
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发表时间：
2015-09-22
期刊：
影响因子：
37.8
通讯作者：
Shi FD
中科院分区：
文献类型：
--
作者：
Zhu Z;Fu Y;Tian D;Sun N;Han W;Chang G;Dong Y;Xu X;Liu Q;Huang D;Shi FD
脑缺血引发的炎症和免疫反应恶化了卒中的临床结局，并导致与静脉注射阿替普酶相关的出血性转化、大量水肿和再灌注损伤。我们评估了免疫调节剂芬戈莫德和阿替普酶联合治疗在症状发作的前4.5小时内治疗的急性缺血性卒中（AIS）患者中是否安全有效，以减轻再灌注损伤。在这项多中心试验中，我们将25例符合条件的大脑前动脉或中动脉闭塞导致的半球缺血性卒中患者随机分配接受阿替普酶单药治疗，或22例患者在缺血性卒中发作后4.5小时内接受阿替普酶联合口服芬戈莫德0.5 mg每日一次，连续3天。与接受阿替普酶单药治疗的患者或接受芬戈莫德与阿替普酶联合治疗的患者相比，第1天的国立卫生研究院卒中量表显示循环淋巴细胞减少、病灶体积缩小（10.1 vs 34.3 ml，P = 0.04）、出血减少（1.2 vs 4.4 ml，P = 0.01）和神经功能缺损减轻（4 vs 2，P =0.02）。此外，在给予芬戈莫德和阿替普酶的患者中，从第1天到第7天的病变生长受到抑制（−2.3 vs 12.1 ml，P < 0.01），第90天的恢复更好（改良兰金量表0-1，73% vs 32%，P < 0.01）。所有患者均未发生严重不良事件。在这项初步研究中，芬戈莫德和阿替普酶联合治疗耐受性良好，减轻了再灌注损伤，改善了AIS患者的临床结局。这些发现需要在进一步的临床试验中进行测试。
Inflammatory and immune responses triggered by brain ischemia worsen clinical outcomes of stroke and contribute to hemorrhagic transformation, massive edema and reperfusion injury associated with intravenous alteplase. We assessed whether a combination of the immune-modulator fingolimod and alteplase is safe and effective in attenuating reperfusion injury in patients with acute ischemic stroke (AIS) treated within the first 4.5 hours of symptom onset. In this multi-center trial, we randomly assigned 25 eligible patients with hemispheric ischemic stroke stemming from anterior or middle cerebral arterial occlusion to receive alteplase alone or 22 patients to receive alteplase plus oral fingolimod 0.5 mg daily for three consecutive days within 4.5 hours of the onset of ischemic stroke. Compared with patients who received alteplase alone or patients who received combination of fingolimod with alteplase exhibited lower circulating lymphocytes, smaller lesion volumes (10.1 vs 34.3 ml, P = 0.04), less hemorrhage (1.2 vs 4.4 ml, p = 0.01) and attenuated neurodeficits in National Institute of Health Stroke Scales (4 vs 2, P =0.02) at day 1. Furthermore, restrained lesion growth from day 1 to day 7 (−2.3 vs 12.1 ml, P < 0.01) with a better recovery at day 90 (modified Rankin Scale 0-1, 73% vs 32%, P < 0.01) was evident in patients given fingolimod and alteplase. No serious adverse events were recorded in all patients. In this pilot study, combination therapy of fingolimod and alteplase was well tolerated, attenuated reperfusion injury and improved clinical outcomes in AIS patients. These findings need to be tested in further clinical trials.