Clinical trial NCT04229264: Efficacy and Safety of Apixaban in Reducing Restenosis and Limb Loss in PAD Patients.
Official title: Efficacy and Safety of Apixaban in Reducing Restenosis and Limb Loss in Subjects With Symptomatic Peripheral Artery Disease (PAD) Undergoing Infrapopliteal Endovascular Peripheral Revascularization Procedures in Patients With Critical Limb
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Critical Limb Ischemia
Keywords: Post-infrapopliteal angioplasty
Lead sponsor: Science Valley Research Institute
Sponsor class: OTHER
Collaborators: name: Wyeth is now a wholly owned subsidiary of Pfizer
First posted: 2020-01-18
Enrollment: 200
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: This study will evaluate the efficacy and safety of apixaban 2.5 mg twice daily plus aspirin compared to the standard treatment (clopidogrel plus aspirin) in patients with critical limb ischemia undergoing infrapopliteal arterial endovascular intervention.

Detailed description: This study is a multicentre, parallel-group, prospective, randomized open-label, blinded-endpoint adjudication, proof-of-concept, and exploratory trial. Two hundred patients will be randomized in a 1:1 ratio, 72 hours after successful infrapopliteal angioplasty for critical limb ischemia. In the study group, patients will receive oral apixaban 2.5mg twice daily plus aspirin 100 mg once-daily for 12 months. In the control group, aspirin 100 mg once-daily will be taken for 1 year on a background of clopidogrel (75mg daily) for the first three months. The primary endpoint is the composite of target lesion revascularization (TLR), major amputation or restenosis/occlusion (RAS) plus MACE (myocardial infarction, stroke, and cardiovascular death) at 12 months. The primary safety endpoint is the composite of major bleeding and clinically relevant non-major bleeding at 12 months.

Eligibility criteria: Inclusion Criteria:

* Written informed consent.
* Age\>18 years old.
* Negative serum pregnancy test (in women of childbearing only).
* Patients submitted to endovascular procedures below-the-knee by not exclusively.
* Patient understands and is willing and able to comply with the study instructions and follow-up visit.
* More than 70% stenosis or occlusion of the three distal arteries including or not the tibiofibular trunk (TFT).
* Tissue loss (Rutherford 5).
* One or more patent vessel of pedal arch.

Exclusion Criteria:

* TASC II D femoral and/or popliteal occlusion.
* Life expectancy less than 1 year.
* Allergy or contraindication to apixaban treatment.
* Allergy or contraindication to dual antiplatelet treatment.
* Creatinine clearance less than 30mL/min.
* Planned major amputation before procedure.
* Hybrid procedure (open and endovascular).
* Use of fibrinolytic in the past 10 days.
* Known HIV infection.
* Liver disease (acute or chronic hepatitis and cirrhosis).
* Drug addiction or alcohol abuse 12 months before the randomization.
* Concomitant medications thatinhibit the CYP 3A4 cytochrome and P glycoprotein (ketoconazole, Iitraconazole, ritonavir).
* Platelets count inferior to 100x109/L.
* INR more than 1.5.
* History or condition with high risk of bleeding: Eg. Trauma within 30 days before randomization, gastrointestinal bleeding 6 month before the randomization, intra-ocular, spinal, intra-articular bleeding (any time before), AV malformation, cerebral aneurysm and hypertension without control.

Primary outcomes:
measure: Restenosis of the treated infrapopliteal artery
timeFrame: 12 months
measure: Major amputation
timeFrame: 12 months
measure: Clinical driven-target lesion revascularization
timeFrame: 12 months
measure: Major cardiovascular events
timeFrame: 12 months
Secondary outcomes:
measure: Bleeding
timeFrame: 12 months
measure: Healing
timeFrame: 12 months
Other outcomes:
Locations:
city: São Paulo
country: Brazil
facility: IAMSPE - Sao Paulo Public Servants Hospital
Study officials:
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