Rationale and design for the study Apixaban versus ClopidoGRel on a background of aspirin in patients undergoing InfraPoPliteal angioplasty for critical limb ischemia: AGRIPPA trial

Abstract

Background: New antithrombotic strategies that reduce primary thrombosis and restenosis might improve vascular outcomes in patients with peripheral artery disease (PAD) undergoing arterial angioplasty. The study objective is to evaluate the potential benefit of apixaban plus aspirin compared with standard of care dual antiplatelet therapy (DAPT) in reducing thrombotic restenosis and artery re-occlusion in patients undergoing endovascular infrapopliteal revascularization. Study design: This multicenter, parallel-group, prospective, randomized, open-label, blinded-endpoint adjudication, proof-of-concept, exploratory trial aims to randomize 200 patients 72 hours after successful infrapopliteal angioplasty for critical limb ischemia (CLI). Patients will be randomly assigned in a 1:1 ratio to receive oral apixaban (2.5 mg twice daily) plus aspirin (100 mg once daily) for 12 months or clopidogrel (75 mg daily) for at least 3 months on a background of aspirin (100 mg once daily) for 12 months. The primary endpoint is the composite of target lesion revascularization (TLR), major amputation, or restenosis/occlusion (RAS) in addition to major adverse cardiovascular events – MACE (myocardial infarction, stroke or cardiovascular death) at 12 months. The primary safety endpoint is the composite of major bleeding or clinically relevant non-major bleeding at 12 months. This study will evaluate the efficacy and safety of apixaban 2.5 mg twice daily plus aspirin compared with DAPT (clopidogrel plus aspirin) in patients with CLI undergoing endovascular infrapopliteal revascularization and might prove the concept of an alternative antithrombotic regimen for these patients to be tested in a future large randomized clinical trial.