Implementation of a Standardized Algorithm for Coronary Calcification With Plaque Modification

Implementation of a Standardized Algorithm for CoronarY CaLcificatiOn With PlaquE Modification Using UltraSound Guidance to Improve Procedural and Clinical Outcomes (CYCLOPES)

In this study, the doctors will follow a set of rules that is called an algorithm. An algorithm is a step-by-step approach that doctors use to guide them when making decisions about the best way to treat their patients. Algorithms are useful because they help doctors decide on the best treatment approach based on the patient's individual circumstances and the best medical evidence available. The algorithm that is being used in this study is called a calcium modification algorithm and it will guide doctors when deciding on the best way to modify or break up the calcium in coronary arteries.

In this study, we aim to prove that the calcium modification algorithm, described above, safely and effectively guides doctors on the best way to modify calcium in patients' coronary arteries. By doing so, it will help doctors in making decisions about patients' treatment during their procedure. It will also help standardise care for patients, so patients receive the same treatment no matter what hospital they are in or what doctor is treating them.

Investigational strategy:

Calcium modification algorithm to guide coronary intervention with an High Definition Intra Vascular Ultrasound (HD IVUS) imaging guided pathway that provides a systematic approach to coronary modification.

Objectives:

The aim of this study is to validate a comprehensive and intravascular imaging-based calcium modification algorithm for the treatment of moderate to severely calcified coronary lesions.

Study Population:

Patients with coronary artery disease with evidence of moderate to severely calcified coronary arterial lesions that are planned for percutaneous intervention requiring calcium modification.

Design:

CYCLOPES is a prospective, multicenter, open-label, single arm trial assessing the feasibility and efficacy of an intracoronary ultrasound guided algorithm for calcium modification in patients undergoing percutaneous coronary intervention (PCI) for chronic calcific coronary artery disease. The study will enrol 500 patients who will undergo PCI with calcium modification.

Participants will be enrolled prospectively in 25 sites in Ireland, Switzerland, the United Kingdom, Spain, France, Italy and Germany (7 countries).

All patients will have coronary angiography (QCA) and intravascular ultrasound (IVUS) imaging with 60MHz HD IVUS of the calcified lesion at baseline. The lesion will be characterized based on calcium distribution and morphology as assessed by HD IVUS. Depending on the specific lesion characteristics, the appropriate method for calcium modification will be chosen and performed in line with the CYCLOPES calcium modification algorithm included in the study protocol.

The calcific lesion will be imaged for a second time by 60MHz HD IVUS following calcium modification. The operator will then proceed, if no further lesion preparation is required, to deploy a bioabsorbable polymer Everolimus eluting stent using standard stenting techniques, post dilatation will be performed at the operator's discretion. The treated lesion will be assessed again using intravascular ultrasound following stent deployment and optimization.

The primary end points will be the post stenting minimal stent area (MSA) at the site of maximum calcification relative to reference lumen area assessed with 60MHz HD IVUS and target lesion failure (TLF) at 1-year post-procedure. All HD IVUS determined endpoints will be assessed at an independent imaging core laboratory.

Participants will be assessed with clinic or phone visits at hospital discharge, 1 month and 12-month time points post procedure.

Inclusion Criteria:

1. Documented myocardial ischaemia.

2. At least one moderate to severely calcified native coronary artery lesion confirmed by QCA and/or 60MHz HD IVUS, with the presence of significant calcium, ≥70% diameter stenosis by visual estimation (in a reference vessel diameter of ≥2.5mm and ≤4.0mm) and TIMI 3 flow at baseline that is suitable for PCI.

   a. Significant calcium at the target lesion site is defined as either: i. The presence of radiopacities involving both sides of the arterial wall >10mm and involving the target lesion on angiography.

   or ii. The presence of >270° arc of superficial calcium on HD intravascular imaging with a length >5mm or the presence of 360° arc of calcium on HD intravascular imaging. [1]

3. It is possible to cross the calcified lesion with a coronary guidewire.

4. Age ≥ 18 years.

5. Patient is willing and able to comply with the study procedures and follow-up.

Exclusion Criteria:

1. Patients with cardiogenic shock.
2. ST-segment elevation myocardial infarction.
3. Instent re-stenosis.
4. Stent thrombosis.
5. Coronary artery dissection.
6. Chronic total occlusion in a major artery.
7. Left ventricular ejection fraction ≤30%. Need for coronary artery bypass graft surgery.

9. Documented allergy to everolimus or to any stent material 10. Any contraindication for dual antiplatelet therapy with aspirin and a P2Y12 inhibitor for at least 3 months (except for patients on oral anticoagulation). 11. For female, pregnancy, breastfeeding or intend to become pregnant within 1 year 12. Life expectancy <1 year. 13. Participation in another study with an investigational product. 14. Inability to provide informed consent.