Rationale and design for the randomized placebo-controlled double-blind trial studying the effect of single antiplatelet therapy (clopidogrel) versus dual antiplatelet therapy (clopidogrel/acetylsalicylic acid) on the occurrence of atherothrombotic events following lower extremity peripheral transluminal angioplasty (CLEAR-PATH)

• Published in: The American heart journal Vol. 273; pp. 121 - 129
• Main Authors: Wegerif, Emilien C.J., Ünlü, Çağdaş, Generaal, Manon I., van den Bor, Rutger M., van de Ven, Peter M., Bots, Michiel L., de Borst, Gert J.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.07.2024; Elsevier Limited
• Subjects: Acetylsalicylic acid; Amputation; Angioplasty; Angioplasty - methods; Anticoagulants; Antiplatelet therapy; Aspirin; Aspirin - administration & dosage; Aspirin - therapeutic use; Bleeding; Cardiovascular disease; Cardiovascular system; Cerebral infarction; Cerebrovascular diseases; Clopidogrel; Clopidogrel - administration & dosage; Clopidogrel - therapeutic use; Coronary artery; Double-Blind Method; Double-blind studies; Dual Anti-Platelet Therapy - methods; Effectiveness; Female; Heart attacks; Hemorrhage - chemically induced; Hemorrhage - epidemiology; Human subjects; Humans; Ischemia; Lower Extremity - blood supply; Male; Males; Medical research; Mortality; Multicenter Studies as Topic; Myocardial infarction; Netherlands - epidemiology; Occlusion; Patient compliance; Peripheral Arterial Disease - therapy; Placebos; Platelet Aggregation Inhibitors - administration & dosage; Platelet Aggregation Inhibitors - therapeutic use; Population studies; Prospective Studies; Quality of life; Questionnaires; Randomized Controlled Trials as Topic; Restenosis; Therapy; Thrombolysis; Thrombolytic drugs; Thrombosis - epidemiology; Thrombosis - etiology; Thrombosis - prevention & control; Vascular diseases; Vein & artery diseases; Netherlands; EVR; ATT; AE; APT; CAD; PPI; MALE; ASA; CVD; PAD; SAPT; MACE; DAPT; PFT
• ISSN: 0002-8703; 1097-6744; 1097-6744
• DOI: 10.1016/j.ahj.2024.04.001

Antiplatelet therapy (APT) is the standard of care after endovascular revascularization (EVR) in patients with peripheral artery disease (PAD). APT aims to prevent both major adverse cardiovascular events (MACE) and major adverse limb events (MALE). Nonetheless, the rates of MACE and MALE after EVR remain high. In coronary artery and cerebrovascular disease, dual APT (DAPT)compared to acetylsalicylic acid alone has been proven to reduce MACE without increasing the risk of major bleeding when applied for a restricted number of weeks. However, within the PAD population, insufficient data are available to understand the potential attributable effect of DAPT over single APT (SAPT). Therefore, prospective randomized studies in targeted study populations are warranted. CLEAR-PATH is a Dutch multicenter, double-blind, placebo-controlled, randomized trial comparing SAPT (clopidogrel 75 mg plus placebo) with DAPT (clopidogrel 75 mg plus acetylsalicylic acid 80 mg) in patients with PAD undergoing EVR. CLEAR-PATH includes a time-to-event analysis with a follow-up of one year. The primary composite efficacy endpoint consists of all-cause mortality, nonfatal stroke, nonfatal myocardial infarction, severe limb ischemia, (indication for) re-intervention due to any symptomatic restenosis, re-occlusion, or due to acute limb ischemia, and major amputation. The primary safety endpoint contains major bleeding following the Thrombolysis in Myocardial Infarction classification. The enrolment started in August 2022. In total 450 primary efficacy outcome events are required which expectedly amounts to 1696 subjects. Recruitment will take approximately 36 months. CLEAR-PATH will assess the efficacy and safety of DAPT compared to SAPT following EVR in PAD patients. : NL80009.041.21.