Efficacy and Safety of Apixaban in Reducing Restenosis and Limb Loss in PAD Patients.

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Critical Limb Ischemia

Intervention / Treatment
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* Drug: Apixaban
* Drug: ASA
* Drug: Clopidogrel 75mg


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Control group<br>Aspirin 100 mg (oral, once-daily) for 1 year plus Clopidogrel 75 mg (oral, once-daily) for 3 months. | Drug: ASA<br>* Acetil Salicilic Acid 100mg once daily for one year<br>Drug: Clopidogrel 75mg<br>* Clopidogrel 75mg once daily for 3 months<br>* Other names: Doppler Ultrasound Follow-up 1, 3, 6 and 12 months;|
| Experimental: Apixaban group<br>Apixaban 2.5 mg (oral, twice daily) for 1 year plus Aspirin 100 mg (oral, once-daily) for 1 year. | Drug: Apixaban<br>* Oral Apixaban 2.5 mg twice daily for one year<br>* Other names: Doppler Ultrasound Follow-up 1, 3, 6 and 12 months;Drug: ASA<br>* Acetil Salicilic Acid 100mg once daily for one year<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Restenosis of the treated infrapopliteal artery | Number of patients with absence of flow or >2.4 sistolic index obtained by Duplex Scan | 12 months | 
| Major amputation | Number of patients who underwent amputation of the leg above the ankle | 12 months | 
| Clinical driven-target lesion revascularization | Number of patients who was submitted by reintervention of the treated infrapopliteal artery based on the clinical status | 12 months | 
| Major cardiovascular events | Number of patients who present one of those: myocardial infarction, stroke and cardiovascular death | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bleeding | Number of patients who present major bleeding (MB) or clinically relevant non-major bleeding, using the ISTH criteria | 12 months | 
| Healing | Time to total healing measured by the Imitomeasure program. | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Post-infrapopliteal angioplasty