Acute Peripheral Arterial Occlusion (acute PAO) is to peripheral vascular disease what acute coronary syndromes are to atherosclerotic heart disease and what stroke is to atherosclerotic cerebrovascular diease. "Leg attack", "heart attack", and "brain attack" alike, require prompt restoration of arterial blood flow in order to affect a minimization of symptoms, tissue damage, morbidity, and mortality.
Conditions
Sponsors
Nuvelo
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: a) The subject (or legally acceptable representative) must give written informed consent b) Age 18 years or older c) Arteriographically confirmed acute PAO of the lower extremity with onset of symptoms within 14 days prior to randomization d) 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). Only Class I subjects with abrupt onset of ischemic rest pain or abrupt onset/progression of lifestyle-limiting claudication are eligible. e) Acute PAO with a need for urgent surgical intervention to restore arterial blood flow in the event of unsuccessful thrombolytic therapy f) Available for follow-up assessments Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: a) 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 b) History of endovascular procedure or open vascular surgery on the index limb within the last 30 days c) History of significant acute or chronic kidney disease that would preclude contrast angiography d) Known allergy to contrast agents e) History of heparin-induced thrombocytopenia (HIT) f) Participation in any study of an investigational device, medication, biologic, or other agent within 30 days prior to randomization g) Any thrombolytic therapy within 5 days prior to randomization h) Past participation in any alfimeprase clinical trial i) Pregnant, lactating, or actively menstruating women and women o 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) j) Investigator inability to advance guidewire through index occlusion k) Any other subject feature that in the opinion of the investigator should preclude study participation
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of alfimeprase compared with placebo as measured by 30 day open vascular surgery free rate;Secondary Objective: To evaluate: • Rate of arterial flow restoration at 4 hours after initiation of study drug • Rate of improvement in index limb ankle-brachial index (ABI) by = 0.15 at 30 days • Change in Walking Impairment Questionnaire functional status scores from baseline at 30 days • Safety ;Primary end point(s): PRIMARY ENPOINTS • 30 day open vascular surgery free rate SECONDRY ENDPOINTS • Rate of arterial flow restoration at 4 hours after the initiation of first dose of study drug • Rate of improvement in ABI at 30 days • Change in WIQ functional status scores from the 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 EXPLORATORY ENDPOINTS • Length of hospital stay up to 30 days • Length of intensive care unit (ICU) stay up to 30 days • Rate of improvement in ABI at 90 and 180 days • Change in WIQ functional status scores from baseline at 90 and 180 days • Adverse events, all cause mortality, surgical and endovascular procedures, and amputation at 90 and 180 days | — |
Countries
Denmark, Finland, Hungary, Netherlands, United Kingdom
Outcome results
None listed