Study Posting (4305) -- Trial #89520, Peripheral Arterial Occlusive Disease, Merrillville, IN

Purpose
The purpose of this research study is to evaluate the safety and effectiveness of study drug intra-thrombus alfimeprase 0.3mg/kg with placebo in acute peripheral arterial occlusion (PAO) as measured by a 30 day open vascular free surgery rate.

Study Type: Interventional
Study Design: Treatment, Randomized, Double-blind, Placebo Control, Parallel Assignment, Safety/Efficacy Study

Official Tittle: Phase 3, Multicenter, Multi-National, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Alfimeprase in Subjects with Acute Peripheral Arterial Occlusion (NAPA-3)

Primary Outcome: 30 day open vascular surgery free rate
Secondary Outcomes: Rate of arterial flow restoration at 4 hours after the initiation of the first dose of study drug; Rate of improvement in index limb ankle-brachial index (ABI) by =0.15 at 30 days; Change in Walking Impairment Questionnaire (WIQ) functional status scores from baseline at 30 days; Adverse events, serious adverse events, major bleeding events, ICH, peripheral arterial embolic events, all cause mortality, surgical and endovascular procedures and amputation up to 30 days.

There is an unmet medical need to improve the therapy of acute peripheral arterial occlusion (PAO). Currently used therapies include open surgery such as thromboembolectomy and thrombolysis with plasminogen activator. Surgery is associated with perioperative morbidity and mortality as well as extended hospitalization. Plasminogen activators are not approved by regulatory agencies for acute PAO and have not been clearly shown to have clinical efficacy. Plasminogen activators can also 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 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 and plasminogen activator exposure.

1. Subject or legally authorized representative must give written informed consent
2. Age 18 or older
3. Arteriographically confirmed Acute PAO of the lower extremity with onset of symptoms within 14 days prior to randomization
4. Acute index limb ischemia classified as SVS/ISCVS Class I or IIA caused by occlusion of a native artery and/or ischemic rest pain or abrupt onset/progression of lifestyle-limiting claudication are eligible.
5. Acute PAO with a need for urgent surgical intervention to restore arterial blood flow in the event of unsuccessful thrombolytic therapy
6. Available for follow-up assessments

1. Contraindication to systemic anticoagulation e.g., history of documented hemorrhage requiring treatment within the past 30 days; history of a hereditary bleeding disorder or known bleeding diathesis; major surgery or trauma, open chest massage, ocular surgery or hemorrhagic retinopathy within the past 30 days; puncture at non-compressible site within 48 hours prior to administration of study drug; and history of stroke, intracranial hemorrhage, or central nervous system structural abnormalities within the past 3 months.
2. History of endovascular procedure or open vascular surgery on the index limb within the last 30 days
3. History of significant acute or chronic kidney disease that would preclude contrast angiography
4. Known allergy to contrast agents
5. History of herparin-induced thrombocytopenia (HIT)
6. Participation in any study of an investigational device, medication, biologic, or other agent within 30 days prior to randomization
7. Any thrombolytic therapy within 5 days prior to randomization
8. Past participation in any alfimeprase clinical trial
9. 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)
10. Investigator inability to advance guidewire through index occlusion
11. Any other subject feature that in the opinion of the investigator should preclude study participation

If you would like to learn more about participating in this study, please send an e-mail message using the form below.

Trial Information

Summary: Study of the Ability of Alfimeprase to Rapidly Dissolve Blood Clots in the Leg and Help Prevent the Need for Surgery on Leg Arteries