International, Multicenter, Double-Blind, Placebo-Controlled, Randomized Phase I/II Trial of Desmoteplase in the Indication of Acute Ischemic Stroke
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 38
- 主要终点
- National Institutes of Health Stroke Scale (NIHSS), Barthel-Index, mRS
研究概览
简要总结
The purpose of this study was to explore trends in safety and efficacy, and to find the optimal dose for the subsequent phase III trial. The decision to initiate the phase III trial will depend on both safety (incidence of symptomatic intracranial hemorrhage) and efficacy (reperfusion measured by MRI and correlating with clinical outcome) profiles. The safety (incidence of symptomatic intracranial haemorrhage) and efficacy (reperfusion measured by MRI and correlating with clinical outcome) profiles gained from this study were the basis of planning the phase III.
详细描述
Acute stroke is the third leading cause of mortality in developed countries and the major medical cause of disability in adults. The outcome can be improved by early treatment with thrombolysis. Alteplase (r-tPA) is the only approved thrombolytic drug in the indication of acute ischemic stroke. However, the use of alteplase is currently restricted by the need to administer it within 3 hours of symptom onset. As the risk of transforming a cerebral infarct into haemorrhage probably rises as the time elapsed increases, a thrombolytic drug that carries a lower risk of haemorrhage than alteplase may offer a wider time-to-treatment window and improve the safety profile.
Desmoteplase (DSPA) with its high fibrin specificity, lack of neurotoxicity, potential neuroprotective effect, non-activation by ß-amyloid, and long terminal half-life may account for an improved safety and efficacy profile within the first 9 hours after onset of symptoms.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •scoring 4 to 20 on the National Institute of Health Stroke Scale (NIHSS)
- •showing a perfusion-diffusion mismatch on MRI of 20 %
- •enrolment within a 3 h to 9 h time window after symptom onset.
- •18-85 years of age
排除标准
- •Participation in any interventional trial in the previous 30 days.
- •Women in the childbearing age.
- •Any history of intracranial hemorrhage, subarachnoid hemorrhage, neoplasm, arteriovenous malformation or aneurysm.
- •Conditions that, according to the judgment of the investigator, might impose an additional risk to any individual stroke patient when receiving study medication (this applied to patients on platelet-function inhibitors as well).
- •MRI exclusion criteria: Evidence of ICH, Evidence of SAH, Signs of extensive early infarction on DWI assessed by evidence of involvement of >1/3 of the middle cerebral artery (MCA) territory. No perfusion deficit, Internal carotid artery (ICA) occlusion ipsilateral to stroke lesion without additional ipsilateral MCA, anterior cerebral artery (ACA) or posterior cerebral artery (PCA) occlusion. Any intracranial pathology that would interfere with the MRI assessment of acute ischemic stroke.
研究组 & 干预措施
1
Desmoteplase 90µg/kg BW
干预措施: Desmoteplase (Drug)
2
Desmoteplase 125 µg/kg BW
干预措施: Desmoteplase (Drug)
3
Placebo
干预措施: Placebo (Drug)
结局指标
主要结局
National Institutes of Health Stroke Scale (NIHSS), Barthel-Index, mRS
时间窗: Day 90
Reperfusion after 4-8 h
时间窗: 8 h
Infarct lesion volume after 30 days
时间窗: Day 30
Safety & pharmacokinetic outcomes
时间窗: Day 90
次要结局
未报告次要终点