Antiplatelet Strategy for Peripheral Arterial Interventions for Revascularization of Lower Extremities (ASPIRE PAD)

To evaluate whether clopidogrel 75 mg QD on a background of ASA 75-100 mg/d for 12 months or
for 1 month will lead to an increased rate of primary patency, limb salvage, freedom form
ischemic stroke and survival, in patients receiving endovascular treatment of PAD.

Trial hypothesis We hypothesize that DAPT with ASA and clopidogrel administered for 12
months following iliac, FP or BTK endovascular intervention will improve primary patency,
limb salvage, freedom form ischemic stroke and survival, in patients with symptomatic PAD.

Trial endpoints Clinical endpoints will be analyzed in all subjects who are enrolled,
regardless of whether the trial treatment administered successfully completed for the
desired duration. A subject will be considered enrolled in the trial when he/she is
randomized to one of the treatment arms of the study. All endpoints are subject-based unless
otherwise specified.

The primary endpoint is a subject-based 12-month endpoint of the first occurrence of index
limb arterial occlusion, surgical intervention, endovascular intervention, amputation of the
affected limb (primary patency and limb salvage), MI, ischemic stroke or death (survival)
The secondary endpoints are subject-based 12-month endpoints that include: (a) the first
occurrence of any individual component of the primary endpoint, (b) the first occurrence of
the following during follow-up: cardiovascular death, or MI, or ischemic stroke, or any
amputation above the ankle and (c) severe bleeding defined according to the Global
Utilization of Streptokinase and Tissue plasminogen activator for Occluded coronary arteries
(GUSTO)classification The tertiary endpoint is based on 12-month moderate bleeding according
to the GUSTO classification

Inclusion Criteria:

- General:

- Signed informed consent

- At least 18 years old

- Documented symptomatic iliac, femoropopliteal (FP) or below-the knee artery
(BTK) atherosclerotic disease (Rutherford/Becker category 2, 3 or ≥4)

- Undergone clinically indicated uncomplicated endovascular intervention to one or
more locations of the iliac, femoropopliteal below-the knee arteries

- Estimated survival ≥1 year in the judgment of the primary operator

- Pre-index procedure use of ASA, clopidogrel or both at any dose

Angiographic:

- De novo or restenotic lesions in the common and/or external iliac artery, superficial
femoral artery (SFA), popliteal artery, tibio-peroneal (TP) trunk, anterior tibial
(AT) artery, peroneal artery (PA) or posterior tibial (PT) artery (applies to all
target lesions if multiple)

- Subjects with multiple planned procedures can be enrolled after the completion of the
last planned procedure.

Exclusion Criteria:

- General:

- Complicated qualifying procedure (perforation, flow limiting dissection, distal
embolization requiring re-intervention, need for repeat endovascular, surgical
revascularization, amputation or blood transfusion prior to hospital discharge
following index procedure

- Extended hospital stay >7 days following the index procedure

- Allergy to aspirin or clopidogrel

- MI or PCI with DES within the past 9 months

- Life expectancy less than 12 months due to other medical co-morbid condition(s)
that could limit the subject's ability to participate in the trial, limit the
subject's compliance with the follow-up requirements, or impact the scientific
integrity of the trial

- Known hypersensitivity or contraindication to contrast dye that, in the opinion
of the investigator, cannot be adequately pre-medicated.

- Intolerance to antiplatelet, anticoagulant, or thrombolytic medications

- Platelet count <90,000 mm3 or >600,000 mm3

- Serum creatinine >2.5 mg/dL

- Dialysis-dependent end stage renal disease

- Pregnancy

- Current participation in another drug or device trial that requires interruption
of dual-antiplatelet therapy with aspirin or clopidogrel for <1y

- Planned surgeries, endovascular or other non-vascular or cardiac procedures

- Warfarin or other chronic oral anticoagulant use

- Contraindication(s) to the use of antithrombin or antiplatelet agents (history
of intra-cerebral bleed, presence of intracerebral mass, recent or <6 weeks
gastrointestinal bleed, blood transfusion within the last 6 weeks, any trauma
requiring surgery or blood transfusion within the last 4 weeks or any surgical
procedure within the last 4 weeks.

Angiographic:

Angiographic:

- Endovascular intervention to iliac, FB or BTK artery bypass graft

- Persistent, intraluminal thrombus of the proposed target lesion at the completion of
the index procedure

- Perforated vessel as evidenced by extravasation of contrast media

- Vascular graft, aneurysm or postsurgical stenosis of the target vessel