Clinical trial NCT00338585: Study of Alfimeprase's Ability to Dissolve Blood Clots in the Leg and Help Prevent the Need for Surgery
Official title: 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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Arterial Occlusive Diseases
Keywords: PAO
acute peripheral arterial occlusion
thrombolysis
blood clot
leg attack
alfimeprase
thrombus
embolism
thromboembolism
claudication
thrombolytic
thrombosis
plasminogen activator
arterial flow
Lead sponsor: ARCA Biopharma, Inc.
Sponsor class: INDUSTRY
First posted: 2006-06-20
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* Age 18 or older
* Arteriographically confirmed acute PAO of the 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). Only Class I subjects with abrupt onset of ischemic rest pain or abrupt onset/progression of lifestyle-limiting claudication are eligible
* Acute PAO with a need for urgent surgical intervention to restore arterial blood flow in the event of unsuccessful thrombolytic therapy
* Available for follow-up assessments

Exclusion Criteria:

* Contraindication to systemic anticoagulation
* History of endovascular procedure or open vascular surgery on the index limb within the past 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
* Participation in any study of an investigational device, medication, biologic, or other agent within 30 days prior to randomization
* Any thrombolytic therapy within 5 days prior to randomization
* Past participation in any alfimeprase trial
* Pregnant, lactating, or actively menstruating women or women of childbearing potential who are not using adequate contraceptive precautions
* Investigator inability to advance guidewire through index occlusion
* Any other subject feature that in the opinion of the investigator should preclude study participation

Primary outcomes:
Secondary outcomes:
measure: rate of arterial flow restoration
measure: rate of improvement in index limb ABI
measure: change in WIQ functional status scores
measure: AEs and SAEs
measure: major bleeding events
measure: ICH
measure: peripheral arterial embolic events
measure: all cause mortality
measure: surgical and endovascular procedures
measure: amputation
measure: changes in chemistry, hematology, and coagulation parameters based on central laboratory measurements
measure: anti-alfimeprase antibody
Other outcomes:
Locations:
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
Study officials:
affiliation: ARCA Biopharma, Inc.
name: Mohammad Hirmand, MD
role: STUDY_DIRECTOR
References: