A Phase 2, Randomized, Open-label (With Blinded Plasminogen Activator and Placebo Control Groups) Study to Evaluate the Effects of Different Intra-thrombus Infusion Regimens of Plasmin (Human) Compared to Plasminogen Activator and Placebo In Patients With Acute Lower Extremity Native Artery or Bypass Graft Occlusion
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 174
- 试验地点
- 39
- 主要终点
- The Proportion of Subjects With >50% Thrombolysis
研究概览
简要总结
The primary purpose of this Phase 2 study is to optimize Plasmin delivery by comparing different delivery regimens in patients with peripheral arterial occlusion. The study includes a blinded plasminogen activator treatment group and a blinded plasminogen activator placebo group. The study will also assess safety and tolerability of Plasmin at 150 and 250 mg doses.
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
- None
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
- •Unilateral limb ischemia - Society of Vascular Surgery Categories I and IIa
- •Onset of symptoms less than or equal to 14 days
- •Thrombosed infrainguinal bypass graft or native artery
- •Diagnosis by arteriography of occlusive thrombus in graft or artery
- •Ability to embed the infusion catheter into the thrombus
- •Women of childbearing potential must use contraception and have a negative pregnancy test
排除标准
- •Any medical or social condition that may interfere with study participation
- •Women who are pregnant or lactating
- •Hemorrhagic stroke history
- •Thrombotic or embolic stroke or cerebrovascular events (including transient ischemic attack) within one year
- •Intracranial or spinal neurosurgery, or severe intracranial trauma in the last 3 months
- •Major surgery, organ biopsy, or major trauma within the past 10 days
- •Lumbar puncture or non-compressible arterial puncture in the past 10 days
- •Intraocular surgery within the past 10 days
- •Active gastrointestinal or organ bleeding
- •Uncontrolled arterial hypertension (systolic blood pressure >180 mmHg or diastolic blood pressure >110 mmHg)
- •Known intracranial neoplasm, aneurysm, or arteriovenous malformation
- •Current bleeding diathesis
- •Platelet count <75 x 10e9/L
- •Active graft infection
- •Occlusion occurred within one month of synthetic graft placement
- •Occlusion occurred within 6 months of autologous graft placement
- •A sequential composite graft with dual outflows to correct multiple occlusions
- •Medically unable to tolerate an open vascular procedure
- •Known prothrombotic state
- •Hemoglobin <10.0 g/dL
- •Impaired renal function or renal disease that constitutes a contraindication to contrast angiography, including creatinine >2.0 mg/dL
- •Treatment with a full dose plasminogen activator (PA) within the last 48 hours
- •Treatment with a glycoprotein IIb/IIIa class of platelet inhibitor within the past 5 days
- •Treatment with oral anticoagulants, and with an international normalized ratio of >1.7
研究组 & 干预措施
Plasminogen Activator Blinded Group E
PA administered for five hours at a dose and volume according to the Investigator's clinical judgement/standard practice
干预措施: Plasminogen Activator (Biological)
PA Placebo Blinded Treatment Arm F
PA placebo (normal saline for injection) administered for five hours at a dose and volume according to the Investigator's clinical judgement/standard practice for PA administration
干预措施: Placebo (Other)
Plasmin Open-label Treatment Group M
Open-label 250 mg Plasmin administered without pulsing; 5-hour infusion using 30 mL/hour infusion rate with balloon occlusion catheter
干预措施: Plasmin (Biological)
Plasmin Open-label Treatment Group J
Open-label 150 mg Plasmin administered without pulsing; 2-hour infusion using 35 mL/hour infusion rate with balloon occlusion catheter
干预措施: Plasmin (Biological)
Plasmin Open-label Treatment Group I
Open-label 150 mg Plasmin administered without pulsing; 5-hour infusion using 30 mL/hour infusion rate with balloon occlusion catheter
干预措施: Plasmin (Biological)
Plasmin Open-label Treatment Group H
Open-label 150 mg Plasmin administered without pulsing; 2-hour infusion using 75 mL/hour infusion rate
干预措施: Plasmin (Biological)
Plasmin Open-label Treatment Group G
Open-label 150 mg Plasmin administered without pulsing; 5-hour infusion using 60 mL/hour infusion rate
干预措施: Plasmin (Biological)
Plasmin Open-label Treatment Group D
Open-label 150 mg Plasmin administered with proximal pulse; 2-hour infusion using 35 mL/hour infusion rate
干预措施: Plasmin (Biological)
Plasmin Open-label Treatment Group C
Open-label 150 mg Plasmin administered with proximal pulse; 5 hour infusion using 30 mL/hour infusion rate.
干预措施: Plasmin (Biological)
Plasmin Open-label Treatment Group B
Open-label 150 mg Plasmin administered with initial proximal pulse; 5-hour infusion using 15 mL/hour infusion rate
干预措施: Plasmin (Biological)
Plasmin Open-label Treatment Group A
Open-label 150 mg Plasmin administered without initial proximal pulse; 5-hour infusion using 10 mL/hour infusion rate.
干预措施: Plasmin (Biological)
结局指标
主要结局
The Proportion of Subjects With >50% Thrombolysis
时间窗: 5 hours (Treatment Groups A, B, C, G, I, M) or 2 hours (Treatment Groups D, H, J)
The proportion of subjects with \>50% thrombolysis at the end of treatment compared to baseline by arteriography.
次要结局
- The Incidence of Major and Minor Bleeding Events, Deaths, Adverse Events, Serious Adverse Events, and Abnormal Laboratory Values as a Measure of Safety and Tolerability.(30 days)