Intravascular Lithotripsy in Comparison to Rotational Atherectomy: An Evaluation by OFDI

Study Overview
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Brief Summary
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The ICARE trial will aim to assess the efficacy of rotational atherectomy by Rotablator and Intravascular Lithotripsy by C2 Shockwave Medical® (IVL) in a randomized fashion in highly calcified lesions measured by final minimal stent area (MSA) on Optical Frequency Domain Imaging (OFDI). The investigator hypothesize that there will be no significant difference in final MSA in OFDI between the two groups after angioplasty with a last generation drug eluting stent ULTIMASTER TANSEI.

Detailed Description
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Calcified coronary lesions will increase in daily percutaneous coronary intervention regarding the significant epidemiological increase of factors leading to coronary calcifications, such as hypertension, aging, and diabetes. Furthermore, calcified lesions are underdiagnosed in angiography as shown by intra-coronary imaging studies (either by OCT or IVUS), which reported that significant calcium deposits might be present in 76-83% of lesions. Calcified lesions are associated with a larger amount of periprocedural complications, as well as a poorer clinical prognosis. Standard techniques to prep the calcified plaque, such as rotational or orbital atherectomy, still have low penetration and are associated with an increase in periprocedural complications without clear clinical evidence of efficacy. More recently, there has been a growing interest in intravascular lithotripsy (IVL), which appears as an appealing option with recently published data with evidence for a safe procedure but without robust data on efficacy (sample size population, debatable effectiveness endpoint…). Although the European Society of Cardiology highlights in the latest myocardial revascularization guidelines the need for lesion preparation before stent implantation on short- and long-term clinical outcomes, no specific recommendation has been given on the use of the dedicated devices to prepare the plaque, including atherectomy, which is left to the operator assessment.

Official Title
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Intravascular Lithotripsy in Comparison to Rotational Atherectomy: An Evaluation by OFDI

Conditions
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Intravascular Lithotripsy; Rotational Atherectomy; OFDI

Intervention / Treatment
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* Device: Intravascular Lithotripsy
* Device: Rotational Atherectomy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient ≥ 18 years old Subjects with native coronary artery disease (including stable or unstable angina and silent ischemia) suitable for Percutaneous Coronary Intervention (PCI) For patients with unstable ischemic heart disease, biomarkers (troponin or CK-MB) must be less than or equal to the upper limit of the lab (URL) normal within 12 hours prior to the procedure The target lesion must be a de novo coronary lesion that has not been previously treated with any interventional procedure Single de novo target lesion stenosis of protected LMCA, or LAD, RCA, or LCX (or of their branches) with: Stenosis of ≥70% and <100% or Stenosis ≥50% and <70% (visually assessed) with evidence of ischemia via positive stress test, or fractional flow reserve value ≤0.80 The target vessel reference diameter must be ≥2.5 mm and ≤4.0 mm The lesion length must not exceed 40 mm The target vessel must have TIMI flow 3 at baseline Evidence of calcification at the lesion with a B or C Mintz classification site: B: Moderate calcification: radiopacities are noted only during the cardiac cycle before contrast injection C: severe calcification: radiopacities are seen without cardiac motion, also before contrast injection, usually affecting both sides of the arterial lumen. Ability to pass a 0.014 guidewire across the lesion Ability to cross target lesion with a 2 mm balloon Patient insured under the French healthcare system (Régime National Assurance Maladie) Lesions in non-target vessels requiring PCI may be treated either: a. >30 days prior to the study procedure if the procedure was unsuccessful or complicated; or b. >24 hours prior to the study procedure if the procedure was successful and uncomplicated (defined as a final lesion angiographic diameter stenosis <30% and TIMI 3 flow (visually assessed) for all non-target lesions and vessels without perforation, cardiac arrest or need for defibrillation or cardioversion or hypotension/heart failure requiring mechanical or intravenous hemodynamic support or intubation, and with no post-procedure biomarker elevation >normal; or c. >30 days after the study procedure d. Could be treated in the same time of the diagnosis coronarography with respect of the delay for the index procedure of the protocol as described above Patient able to assess and understand the risks and benefits, to accept and participate in the study (by signing an informed consent form and knowledgeable of the information letter). Patient accepting the appropriate follow-up as per study definition Exclusion Criteria: Patient age < 18 years The subject is pregnant or nursing Patient refusing to participate in the study or unable to give informed consent (Guardianship, curatorship or judicial safeguard) Any comorbidity or condition which may reduce compliance with this protocol, including follow-up visits The protected subject according to the current legislation (articles L.1121-5 to L.1121-8 of the French Code of Public Health). The subject is participating in another research study involving an investigational agent (pharmaceutical, biologic, or medical device), unless it is authorized by the concomitant study protocol. Unable to tolerate dual antiplatelet therapy (i.e., aspirin, and either clopidogrel, prasugrel, or ticagrelor) for at least 6 months The subject has an allergy to imaging contrast media which cannot be adequately pre-medicated The subject experienced an acute MI (STEMI or non-STEMI) within 30 days prior to index procedure, defined as a clinical syndrome consistent with an acute coronary syndrome with troponin or CK-MB greater than 1 time the local laboratory's upper normal limit New York Heart Association (NYHA) class III or IV heart failure History of a stroke or Transient Ischemic Attack (TIA) within 6 months, or any prior intracranial hemorrhage Active peptic ulcer or upper gastrointestinal (GI) bleeding within 6 months Uncontrolled diabetes defined as an HbA1c >10% Subjects in cardiogenic shock Subject has an active systemic infection on the day of the index procedure with either fever, leukocytosis or requiring intravenous antibiotics Subjects with a life expectancy of less than 1 year Non-coronary interventional or surgical structural heart procedures (e.g., TAVR, MitraClip, LAA, or PFO occlusion…) within 30 days prior to the index procedure Planned non-coronary interventional or surgical structural heart procedures (e.g., TAVR, MitraClip, LAA or PFO occlusion...) Subject refusing or not a candidate for emergency coronary artery bypass grafting (CABG) surgery High SYNTAX Score (≥33) if assessed as a standard of care, unless the local heart team has met and recommends PCI is the most appropriate treatment for the patient Definite or possible thrombus (by angiography or intravascular imaging) in the target vessel Evidence of aneurysm in target vessel within 10 mm of the target Lesion Unprotected left main Target lesion is located in a native vessel that can only be reached by going through a saphenous vein or arterial bypass graft Angiographic evidence of dissection in the target vessel at baseline or after guidewire passage Ejection fraction less than 30 % evaluated in TTE, angiography or MRI Patient suffering of lymphoma, leukemia and other malignancies Patient suffering of liver disease

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
Interventional Model Description: Two parallel arms: Intravascular lithotripsy arm Rotational Atherectomy arm
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intravascular lithotripsy arm<br>Preparation of calcified lesions by intravascular lithotripsy before stenting | Device: Intravascular Lithotripsy<br>* A new device has been designed by Shockwave Medical Inc. for the treatment of calcified vascular lesions to support stent delivery: the C2 Shockwave Medical® (IVL), Inc. coronary lithotripsy system. The system is based on lithotripsy to induce microfractures in the calcified plaque before low-pressure balloon dilation. The C2 Shockwave Medical® coronary lithotripsy (IVL) system consists of an IVL Catheter with two lithotripsy emitters enclosed within an integrated balloon, an IVL Generator, and an IVL Connector Cable.<br>|
| Active Comparator: Rotational Atherectomy arm<br>Preparation of calcified lesions by rotational atherectomy before stenting | Device: Rotational Atherectomy<br>* Rotational Atherectomy is a technique of calcic coronary plaque preparation based on the debulking of superficial calcium by a high-speed burr in order to improve vessel compliance and immediate vessel lumen gain before stenting.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| acute Minimal Stent Area (MSA) defined as in-stent minimal cross-sectional area as assessed by OFDI without In-Hospital MACE (Major Adverse Cardiac Event). | To assess the efficacy of IVL in a randomized fashion comparing to Rotational atherectomy by final Minimal Stent Area (MSA) measurements with Optical Frequency Domain Imaging (OFDI). | Day 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MACE: Cardiac Death, all Myocardial Infarction and Target Lesion Revascularization | To assess safety of IVL in a randomized fashion comparing to Rotational atherectomy by checking the apparition of Major Adverse Cardiac Event (MACE) after 30 days: Cardiac death, all Myocardial Infarction (MI) and Target Lesion Revascularization (TLR) | Day 30 |