Department of Neuroradiology, Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden, Dresden, Germany.
Int J Stroke. 2012 Oct;7(7):589-96. doi: 10.1111/j.1747-4949.2012.00910.x.
Desmoteplase is a novel, highly fibrin-specific thrombolytic agent in phase III of clinical development. In comparison to alteplase, it has high fibrin selectivity, is associated with minimal or no neurotoxicity, and has no apparent negative effect on the blood-brain barrier. The safety and efficacy of desmoteplase is being studied in the Desmoteplase in Acute Ischemic Stroke clinical trial program. Three studies (Dose Escalation Study of Desmoteplase in Acute Ischemic Stroke, Desmoteplase in Acute Ischemic Stroke, and Desmoteplase in Acute Ischemic Stroke-2) have been completed, two large randomized, double-blind, placebo-controlled, phase III trials are ongoing at >200 sites worldwide (Desmoteplase in Acute Ischemic Stroke-3 and Desmoteplase in Acute Ischemic Stroke-4, n = 800; DIAS-3 and DIAS-4), and a randomized, double-blind, placebo-controlled, dose-escalation phase II trial is ongoing in Japan (Desmoteplase in Acute Ischemic Stroke-Japan, n = 48; DIAS-J).
The objective of DIAS-3 and DIAS-4 is to evaluate the safety and efficacy of a single IV bolus injection of 90 μg/kg desmoteplase given three- to nine-hours after onset of ischemic stroke (National Institutes of Health Stroke Scale 4-24, age 18-85 years). The objective of DIAS-J is to evaluate the safety and tolerability of desmoteplase 70 and 90 μg/kg three- to nine-hours after ischemic stroke onset in Japanese patients.
Patients are included with occlusion or high-grade stenosis (thrombolysis in myocardial infarction 0-1) in proximal cerebral arteries on magnetic resonance or computed tomography angiography but excluded with extended ischemic edema on computed tomography or diffusion-weighted imaging.
Desmoteplase is the only thrombolytic agent in late-stage development for acute ischemic stroke that is now tested in patients with proven stroke pathology. The results of the Desmoteplase in Acute Ischemic Stroke clinical trial program will show whether patients with major artery occlusions but not extended ischemic brain damage can be safely and effectively treated up to nine-hours after onset.
地特酶是一种新型的、高度纤维蛋白特异性的溶栓药物，目前处于临床研究的第三阶段。与阿替普酶相比，它具有高纤维蛋白选择性，与最小或无神经毒性相关，并且对血脑屏障没有明显的负面影响。地特酶的安全性和有效性正在 Desmoteplase in Acute Ischemic Stroke 临床试验项目中进行研究。三项研究（急性缺血性卒中地特酶剂量递增研究、急性缺血性卒中地特酶研究和急性缺血性卒中地特酶 2 研究）已经完成，两项大型随机、双盲、安慰剂对照、三期临床试验正在全球 200 多个地点进行（急性缺血性卒中地特酶 3 研究和急性缺血性卒中地特酶 4 研究，n=800；DIAS-3 和 DIAS-4），一项随机、双盲、安慰剂对照、剂量递增二期临床试验正在日本进行（急性缺血性卒中地特酶日本研究，n=48；DIAS-J）。
DIAS-3 和 DIAS-4 的目的是评估在缺血性卒中发作后 3 至 9 小时给予 90μg/kg 地特酶单次静脉推注的安全性和有效性（国立卫生研究院卒中量表 4-24，年龄 18-85 岁）。DIAS-J 的目的是评估在缺血性卒中发作后 3 至 9 小时给予日本患者地特酶 70μg/kg 和 90μg/kg 的安全性和耐受性。
患者纳入标准为磁共振或计算机断层血管造影显示近端脑动脉闭塞或重度狭窄（心肌梗死溶栓治疗 0-1），但排除计算机断层或弥散加权成像显示广泛缺血性水肿的患者。
地特酶是唯一一种在晚期急性缺血性卒中开发的溶栓药物，目前正在有明确卒中病理的患者中进行测试。Desmoteplase in Acute Ischemic Stroke 临床试验项目的结果将表明，对于有大血管闭塞但无广泛脑缺血损伤的患者，能否在发病后 9 小时内安全有效地进行治疗。
