PROMUS Element Plus US Post-Approval Study

Study Overview
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Brief Summary
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This study is designed to observe clinical outcomes in patients receiving the PROMUS Element Plus Everolimus-Eluting Platinum Chromium Coronary Stent System in routine clinical practice. Patients will have symptomatic heart disease or documented silent ischemia. This is a prospective, open-label consecutively-enrolling study. Clinical follow-up is through 5 years. Approximately 2,689 patients are to be enrolled in up to 65 centers in the United States.

Detailed Description
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The wide-spread use of drug-eluting stents (DES) has evolved as standard of care in de novo lesions. The PROMUS Element Plus Everolimus-Eluting Platinum Chromium Coronary Stent System is indicated for improving luminal diameter in patients with symptomatic heart disease or documented silent ischemia due to de novo lesions in native coronary arteries ≥2.25 mm to ≤4.00 mm in diameter in lesions ≤34 mm in length. The proposed study will compile real-world clinical outcomes data for the PROMUS Element Plus Everolimus-Eluting Platinum Chromium Coronary Stent System in routine clinical practice. Patients enrolled in this study are expected to follow antiplatelet therapy recommendations per American College of Cardiology (ACC)/American Heart Association (AHA)/Society for Cardiovascular Angiography and Interventions (SCAI) guidelines for percutaneous coronary intervention (PCI). Recommended medications include aspirin, which should be taken for 3 days prior to the procedure or as a peri-procedural loading dose and then continued indefinitely. Additionally, one of the following P2Y12 antagonists may be given in a peri-procedural loading dose and in a maintenance dose per physician discretion: clopidogrel, prasugrel, ticagrelor, or ticlopidine.

Official Title
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A U.S. Post-Approval Study of the PROMUS Element™ Plus Everolimus-Eluting Platinum Chromium Coronary Stent System

Conditions
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Coronary Artery Disease

Intervention / Treatment
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* Device: PROMUS Element Plus Coronary Stent System
* Drug: Aspirin
* Drug: P2Y12 antagonist


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The population will include consecutive, consented patients. Exclusion Criteria: There are no exclusion criteria in this all-comers study.
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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PROMUS Element<br>Subjects who receive the PROMUS Element everolimus-eluting coronary stent | Device: PROMUS Element Plus Coronary Stent System<br>* PROMUS Element is a device/drug combination product composed of two components, a device (coronary stent) and a drug product (a formulation of everolimus contained in a polymer coating).<br>* Other names: PROMUS Element stent;Drug: Aspirin<br>* Aspirin should be taken daily (81 mg) for 3 days prior to the procedure or as a peri-procedural loading dose of 250-500 mg. A maintenance dose of aspirin of at least 81 mg daily, or as indicated by the treating physician, should be continued indefinitely.<br>* Other names: Acetyl salicylic acid;Drug: P2Y12 antagonist<br>* Patients to take one of the following P2Y12 antagonists; maintenance doses to be continued per ACC/AHA/SCAI guidelines for PCI. Clopidogrel: Per treating physician, peri-procedural loading dose (300-600 mg), subsequent maintenance dose (75 mg daily) Prasugrel: Per treating physician, peri-procedural loading dose (60 mg), subsequent maintenance dose (10 or 5 mg daily per product labeling) Ticagrelor: Per treating physician, peri-procedural loading dose (180 mg), subsequent maintenance dose (90 mg 2x daily); maintenance aspirin doses >100 mg may reduce ticagrelor effectiveness and should be avoided. Ticlopidine: Per treating physician, if allergy/intolerance to clopidogrel, prasugrel, and/or ticagrelor, loading dose (500 mg), subsequent maintenance dose (250 mg 2x daily)<br>* Other names: BRILINTA (ticagrelor);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cardiac Death or Myocardial Infarction Rate in PLATINUM-like Patients | Cardiac death or myocardial infarction rate at 12 months post implantation in PLATINUM-like patients (no acute myocardial infarction, graft stenting, chronic total occlusion, in-stent restenosis, failed brachytherapy, bifurcation, ostial lesion, severe tortuosity, moderate/severe calcification, 3-vessel stenting, cardiogenic shock, left main disease, or acute/chronic renal dysfunction; lesion length ≤28 mm with reference vessel diameter ≥2.25 mm and <2.5 mm, or lesion length ≤24 mm with diameter ≥2.5 mm and ≤4.25 mm); statistical testing will assess if rate meets the performance goal (3.2%) | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Definite + Probable Stent Thrombosis (ST) Rate Based on Academic Research Consortium (ARC) Definition in PLATINUM-like Patients | ARC definite/probable ST rate in PLATINUM-like patients (no acute myocardial infarction, graft stenting, chronic total occlusion, in-stent restenosis, failed brachytherapy, bifurcation, ostial lesion, severe tortuosity, moderate/severe calcification, 3-vessel stenting, cardiogenic shock, left main disease, or acute/chronic renal dysfunction; lesion length ≤28 mm with reference vessel diameter ≥2.25 mm and <2.5 mm, or lesion length ≤24 mm with diameter ≥2.5 mm and ≤4.25 mm); statistical testing will assess if the annual ST rate increase after the first year meets the performance goal (1.0%) | 12 months | 
| Definite + Probable Stent Thrombosis (ST) Rate Based on Academic Research Consortium (ARC) Definition in All Patients | DEFINITE ST: acute coronary syndrome and angiographic or pathologic evidence of stent thrombosis; PROBABLE ST: unexplained death within 30 days or target-vessel infarction without angiographic information ARC ST is reported as a cumulative value at different time points and within the different separate time points. Time 0 is the time point after the guide catheter has been removed. Acute ST: 0-24 hours after stent implantation; Subacute ST: >24 hours to 30 days post; late ST: >30 days to 1 year post; Very late ST: >1 year post; NOTE: Acute/subacute can be replaced by early ST (0-30 days) | ≤24 hours, 30 days, 180 days, annually through 5 years | 
| Rate of Longitudinal Stent Deformation | Compression/elongation of a stent along its long axis resulting from interaction with an ancillary device (e.g., guide catheter) which catches the stent end or an internal stent strut; can occur with advancement or withdrawal of ancillary device. Under fluoroscopy, longitudinal compression usually results in increased strut density and elongation in decreased strut density ('pseudo-fracture'); both can occur in the same stent. | Index Procedure | 
| Major Adverse Cardiac Event Rate (MACE) | Composite of cardiac death, myocardial infarction, and target vessel revascularization | ≤24 hours, 30 days, 180 days, annually through 5 years | 
| Rate of Major Adverse Cardiac Events Related to the PROMUS Element Stent | Composite of cardiac death, myocardial infarction, and target vessel revascularization related to the PROMUS Element stent | ≤24 hours, 30 days, 180 days, annually through 5 years | 
| Myocardial Infarction (MI) Rate | New Q-waves in ≥2 leads lasting ≥0.04 sec with creatine kinase myoglobin band(CK-MB) or troponin >upper limit of normal(ULN); if no new Q-waves total CK levels >3×ULN (peri-percutaneous coronary intervention [PCI]) or >2×ULN (spontaneous) with elevated CK-MB or troponin >3×ULN (peri-PCI) or >2×ULN (spontaneous) plus ≥one of the following: ECG changes indicating new ischemia (new ST-T changes, left bundle branch block), imaging evidence of new loss of viable myocardium, new regional wall motion abnormality. Similar for MI diagnosis post coronary artery bypass graft with CK-MB or troponin >5×ULN | ≤24 hours, 30 days, 180 days, annually through 5 years | 
| Rate of Myocardial Infarction (MI) Events Related to the PROMUS Element Stent | New Q-waves in ≥2 leads lasting ≥0.04 sec with creatine kinase myoglobin band(CK-MB) or troponin >upper limit of normal(ULN); if no new Q-waves total CK levels >3×ULN (peri-percutaneous coronary intervention [PCI]) or >2×ULN (spontaneous) with elevated CK-MB or troponin >3×ULN (peri-PCI) or >2×ULN (spontaneous) plus ≥one of the following: ECG changes indicating new ischemia (new ST-T changes, left bundle branch block), imaging evidence of new loss of viable myocardium, new regional wall motion abnormality. Similar for MI diagnosis post coronary artery bypass graft with CK-MB or troponin >5×ULN | ≤24 hours, 30 days, 180 days, annually through 5 years | 
| Cardiac Death Rate | Cardiac death is defined as death due to any of the following: acute myocardial infarction; cardiac perforation/pericardial tamponade; arrhythmia or conduction abnormality; cerebrovascular accident through hospital discharge or cerebrovascular accident suspected of being related to the procedure; death due to complication of the procedure, including bleeding, vascular repair, transfusion reaction, or bypass surgery; any death in which a cardiac cause cannot be excluded | ≤24 hours, 30 days, 180 days, annually through 5 years | 
| Rate of Cardiac Death Events Related to the PROMUS Element Stent | Cardiac death is defined as death due to any of the following: acute myocardial infarction; cardiac perforation/pericardial tamponade; arrhythmia or conduction abnormality; cerebrovascular accident through hospital discharge or cerebrovascular accident suspected of being related to the procedure; death due to complication of the procedure, including bleeding, vascular repair, transfusion reaction, or bypass surgery; any death in which a cardiac cause cannot be excluded | ≤24 hours, 30 days, 180 days, annually through 5 years | 
| Target Vessel Revascularization (TVR) Rate | Target vessel revascularization is defined as any attempted or successfully completed percutaneous or surgical revascularization of a target vessel. | ≤24 hours, 30 days, 180 days, annually through 5 years | 
| Rate of Target Vessel Revascularization (TVR) Events Related to the PROMUS Element Stent | Target vessel revascularization is defined as any attempted or successfully completed percutaneous or surgical revascularization of a target vessel. | ≤24 hours, 30 days, 180 days, annually through 5 years | 
| Cardiac Death or Myocardial Infarction (MI) Rate | See individual descriptions of events. | ≤24 hours, 30 days, 180 days, annually through 5 years | 
| Rate of Cardiac Death or Myocardial Infarction Events Related to the PROMUS Element Stent | See individual descriptions of events. | ≤24 hours, 30 days, 180 days, annually through 5 years | 
| Target Vessel Failure (TVF) Rate | Target vessel failure (TVF) is defined as any revascularization of the target vessel, myocardial infarction (MI) related to the target vessel, or death related to the target vessel. For the purposes of this protocol, if it cannot be determined with certainty whether MI or death was related to the target vessel it will be considered TVF. | ≤24 hours, 30 days, 180 days, annually through 5 years | 
| Rate of Target Vessel Failure (TVF) Related to the PROMUS Element Stent | Target vessel failure (TVF) is defined as any revascularization of the target vessel, myocardial infarction (MI) related to the target vessel, or death related to the target vessel. For the purposes of this protocol, if it cannot be determined with certainty whether MI or death was related to the target vessel it will be considered TVF. | ≤24 hours, 30 days, 180 days, annually through 5 years | 
| All Death Rate | All death includes cardiac death and non-cardiac death. | ≤24 hours, 30 days, 180 days, annually through 5 years | 
| Non-cardiac Death Rate | Non-cardiac death is defined as death not due to cardiac causes. Cardiac death is death due to any of the following: acute myocardial infarction; cardiac perforation/pericardial tamponade; arrhythmia or conduction abnormality; cerebrovascular accident through hospital discharge or cerebrovascular accident suspected of being related to the procedure; death due to complication of the procedure, including bleeding, vascular repair, transfusion reaction, or bypass surgery; any death in which a cardiac cause cannot be excluded. | ≤24 hours, 30 days, 180 days, annually through 5 years | 
| All Death or Myocardial Infarction Rate | See description of individual events. | ≤24 hours, 30 days, 180 days, annually through 5 years | 
| Target Vessel Failure (TVF) Rate in PLATINUM-like Medically Treated Diabetic Patients | Any revascularization of the target vessel, myocardial infarction related to the target vessel, or death related to the target vessel. See individual components for descriptions. Statistical testing will determine if the rate meets the performance goal (12.6%) | 12 Months | 
| ARC ST Rate in PLATINUM-like Population. | Using the Academic Research Consortium (ARC) definition, the (definite/probable) stent thrombosis (ST) rate in the PLATINUM-like* population will be analyzed. Statistical testing will be used to determine if the annual increase after the first year in ST rates observed in PLATINUM-like patients meets the performance goal of 1.0% (expected rate of 0.4% + a delta of 0.6%). | Annually through 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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drug-eluting stent, DES, atherosclerosis, everolimus