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)

Emilien C J Wegerif; Çağdaş Ünlü; Manon I Generaal; Rutger M van den Bor; Peter M van de Ven; Michiel L Bots; Gert J de Borst

doi:10.1016/j.ahj.2024.04.001

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)

Am Heart J. 2024 Apr 10:273:121-129. doi: 10.1016/j.ahj.2024.04.001. Online ahead of print.

Authors

Emilien C J Wegerif¹, Çağdaş Ünlü², Manon I Generaal³, Rutger M van den Bor⁴, Peter M van de Ven⁴, Michiel L Bots⁵, Gert J de Borst⁶

Affiliations

¹ Division of Vascular Surgery, University Medical Center Utrecht, Utrecht, The Netherlands.
² Division of Vascular Surgery, Northwest Hospital Group, Alkmaar, The Netherlands.
³ Division of Vascular Surgery, University Medical Center Utrecht, Utrecht, The Netherlands; Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
⁴ Department of Data Science and Biostatistics, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
⁵ Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
⁶ Division of Vascular Surgery, University Medical Center Utrecht, Utrecht, The Netherlands. Electronic address: g.j.deborst-2@umcutrecht.nl.

PMID: 38608997
DOI: 10.1016/j.ahj.2024.04.001

Abstract

Rationale: 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.

Trial design: 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.

Conclusion: CLEAR-PATH will assess the efficacy and safety of DAPT compared to SAPT following EVR in PAD patients.

Trial registration number: NL80009.041.21.