Multi-center Prospective Study to Evaluate Outcomes of the Moderate to Severely Calcified Coronary Lesions (MACE)

Study Overview
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Brief Summary
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The objective of this study is to assess the current standard of care treatment outcome in none/mild, moderate and severely calcified coronary lesions using: A composite of MACE at 30-day and one (1) year post procedure, and Procedural and lesion success

Detailed Description
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This prospective, non-randomized, multi-center study includes subjects who meet all of the inclusion and none of the exclusion criteria and sign the ICF. This study may treat up to approximately 500 subjects at up to 50 active sites in the U.S. Subjects may be followed up to three (3) years. Subjects will be stratified into one (1) of three (3) arms based on the degree of calcification in the coronary lesion as defined by this protocol. The duration of the study is expected to be approximately four (4) years.

Official Title
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Multi-center Prospective Study to Evaluate Outcomes of the Moderate to Severely Calcified Coronary Lesions (MACE)

Conditions
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Coronary Artery Disease

Intervention / Treatment
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* Device: Percutaneous Coronary Intervention


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects must be at least 18 years of age. Subjects must be scheduled for percutaneous coronary revascularization involving stent deployment in de novo coronary lesions. Percutaneous coronary revascularization is defined as treatment with commercially available devices that may include but not limited to balloon angioplasty, cutting balloon, rotablation, etc. followed by the stent placement. Subjects CK-MB must be less than or equal to the upper limit of lab normal value within eight (8) hours prior to procedure. If CK-MB results are not yet available prior to initiating procedure, subjects Troponin I or Troponin T must be less than or equal to the upper limit of lab normal value within eight (8) 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. The target vessel must be a native coronary artery with: A stenosis ≥ 70% and < 100%, or A stenosis ≥ 50% < 70% with evidence of clinical ischemia The target vessel reference diameter must be ≥ 2.5mm and ≤ 4.0 mm. The lesion length must not exceed 40 mm. The target vessel must have a Thrombolysis In Myocardial Infarction (TIMI) flow three (3) at baseline. Exclusion Criteria: Inability to understand the study or a history of non-compliance with medical advice. Unwilling or unable to sign the MACE clinical study ICF. History of any cognitive or mental health status that would interfere with study participation. Currently enrolled in any other pre-approval investigational study. This does not apply to long-term post-market studies unless these studies might clinically interfere with the current study endpoints (e.g., limit use of study-required medication, etc.). Female subjects who are pregnant or planning to become pregnant within the study period. Known hypersensitivity or contraindication to aspirin, heparin, ticlopidine or clopidogrel without adequate alternative medications. Known sensitivity to contrast media, which cannot be adequately pre-medicated. Diagnosed with chronic renal failure unless under hemodialysis, or has a serum creatinine level >2.5 mg/dl. History of major cardiac intervention within 30-day, not including a PCI procedure for a staging purpose. Evidence of heart failure by one of the following: i. Left Ventricular Ejection Fraction (LVEF) ≤ 25% ii. New York Heart Association (NYHA) class III or IV iii. Clinical symptoms History of a stroke or transient ischemic attack (TIA) within six (6) months Active peptic ulcer or upper gastrointestinal (GI) bleeding within six (6) months. History of bleeding diathesis or coagulopathy or intention to refuse blood transfusion if one should become necessary. Concurrent medical condition with a life expectancy of < 36 months. History of immune deficiency. Uncontrolled insulin dependent diabetes. Evidence of active infections on the day of the index procedure. Subject has planned cardiovascular intervention within 60 days post index procedure. Subject with angiographically confirmed evidence of more than two (2) lesions within one (1) vessel or more than one (1) vessel requiring intervention, unless the treatment is staged. See Section 10.1 for more details. Target lesion is located in a native vessel distal to anastomosis with a saphenous vein graft or Left Internal Mammary Artery/ Right Internal Mammary Artery (LIMA/RIMA) bypass. Target vessel has angiographically visible or suspected thrombus. Target vessel appears to be/is excessively tortuous at baseline. Target lesion is an ostial location (within 5mm of ostium) or an unprotected left main lesion. Target lesion is a bifurcation (side branch ≥ 1.5mm). Treatment of the target lesion with the CSI coronary Diamondback Orbital Atherectomy System (OAS).

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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| None/mild calcification<br>Presence of readily apparent radiopacities within the vascular wall at the site of the stenosis. | Device: Percutaneous Coronary Intervention<br>* Any Food and Drug Administration (FDA) commercially available device for treating none/mild, moderate, and severe calcified coronary lesions, with the exception of CSI's Coronary Orbital Atherectomy System (OAS).<br>|
| Moderate Calcification<br>Presence of radiopacities only during the cardiac cycle before contrast injection with calcium extended partially into the target lesion. | Device: Percutaneous Coronary Intervention<br>* Any Food and Drug Administration (FDA) commercially available device for treating none/mild, moderate, and severe calcified coronary lesions, with the exception of CSI's Coronary Orbital Atherectomy System (OAS).<br>|
| Severe calcification<br>Presence of radiopacities noted without cardiac motion prior to contrast injection involving both sides of the arterial wall in at least one location, total length of calcium (including segmented) must be at least 15mm and extend partially into the target lesion. | Device: Percutaneous Coronary Intervention<br>* Any Food and Drug Administration (FDA) commercially available device for treating none/mild, moderate, and severe calcified coronary lesions, with the exception of CSI's Coronary Orbital Atherectomy System (OAS).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MACE at 30 Days | A Kaplan-Meier analysis was performed to determine the percent probability that a study participant experienced a major adverse cardiac event through 30 days. 30-day MACE is composed of: Cardiac death Myocardial Infarction (MI) - defined as a Creatine Kinase Myocardial-Band Isoenzyme (CK-MB) level greater than three (3) times the Upper Limit of Lab Normal (ULN) value with or without new pathologic Q wave Target Vessel Revascularization (TVR) - defined as a revascularization at the target vessel (inclusive of the target lesion) after the completion of the index procedure | 30 days post procedure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MACE at One (1) Year | A Kaplan-Meier analysis was performed to determine the percent probability that a study participant experienced a major adverse cardiac event through 1 year. 1-year MACE is composed of: Cardiac death Myocardial Infarction (MI) - defined as a Creatine Kinase Myocardial-Band Isoenzyme (CK-MB) level greater than three (3) times the Upper Limit of Lab Normal (ULN) value with or without new pathologic Q wave Target Vessel Revascularization (TVR) - defined as a revascularization at the target vessel (inclusive of the target lesion) after the completion of the index procedure | One (1) year post procedure | 
| Procedural Success | Procedural success is defined as success in facilitating stent delivery with a residual stenosis of <50% and without the occurrence of an in-hospital MACE. | Participants were followed from baseline procedure through hospital discharge, an expected average of 24 hours | 
| Lesion Success | Lesion success is defined as success in facilitating stent delivery with a post-procedural result of <50% residual stenosis for a given lesion treated during the procedure without severe angiographic complications. | During the procedure |