Phase 3, Multicenter, Multi-National, Randomized, Partial Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Alfimeprase in Subjects With Acute Peripheral Arterial Occlusion
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 300
- 试验地点
- 1
- 主要终点
- 30 day open vascular surgery free rate
研究概览
简要总结
The purpose of this study is to directly compare the safety and efficacy of intra-thrombus alfimeprase 0.3 mg/kg with placebo in acute peripheral arterial occlusion (PAO) as measured by a 30 day open vascular free surgery rate.
详细描述
There is an unmet medical need to improve thrombolytic therapy in acute peripheral arterial occlusion (PAO). Currently used plasminogen activators can result in increased circulating levels of plasmin that result in a systemic "lytic state" that does not distinguish between physiologic and pathologic thrombosis. In general, mean plasminogen activator infusion durations of greater than 24 hours in order to achieve successful thrombolysis are problematic in a disease where delayed restoration of arterial flow can lead to irreversible ischemic damage. A direct thrombolytic agent like alfimeprase, with a rapid mechanism of action and a potentially safer bleeding risk profile, could facilitate a rapid restoration of arterial flow and avoidance of open vascular surgery.
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
- Double
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Must give written informed consent
- •Ages 18 or older
- •Acute PAO of a lower extremity with onset of symptoms within 14 days prior to randomization
- •Acute index limb ischemia classified as SVS/ISCVS Class I or IIA caused by occlusion of a native artery and/or bypass graft (vein or prosthetic)
- •Need for open vascular surgical intervention in the event of unsuccessful thrombolysis
- •Available for follow-up assessments
排除标准
- •Contraindication to systemic anticoagulation
- •History of endovascular procedure or open vascular surgery on the index limb within the last 30 days
- •History of significant acute or chronic kidney disease that would preclude contrast angiography
- •Known allergy to contrast agents
- •History of heparin-induced thrombocytopenia (HIT)
- •Participation in any study of an investigational device, medication, biologic, or other agent within 30 days prior to randomization
- •Any thrombolytic therapy within 30 days prior to randomization
- •Past participation in any alfimeprase clinical trial
- •History of hypersensitivity to aspirin
- •Pregnant, lactating, or actively menstruating women and women of child-bearing potential who are not using adequate contraceptive precautions (e.g. intrauterine device, oral contraceptives, barrier methods, or other contraception deemed adequate by the investigator)
- •Uncontrolled hypertension: systolic blood pressure (BP) > 180 mmHg, or diastolic BP > 110 mmHg at the time of baseline assessment
- •Hematocrit < 30%; subjects with a low hematocrit who are not actively bleeding can be entered into this study if after transfusion their hematocrit is >= 30%
- •Platelet count <100 X 10(9)/L on baseline labs
- •Investigator inability to advance guidewire through index occlusion
- •Medically unable to withstand an open vascular surgical procedure
- •Any other feature that, in the opinion of the investigator, should preclude study participation
结局指标
主要结局
30 day open vascular surgery free rate
次要结局
- Rate of arterial flow restoration at 4 hours after initiation of study drug
- Rate of improvement in index limb ABI by >=0.15 at 30 days
- Change in index limb pain severity score at 30 days
- Length of intensive care unit (ICU) stay
- Safety
- Change in the severity of planned surgical procedures at 30 days
- 30 day open vascular surgery free survival rate
- Length of hospital stay