XIENCE 90: A Safety Evaluation of 3-month DAPT After XIENCE Implantation for HBR Patients.

Coronary Artery Lesions Clinical Trial

Official title:

A Safety Evaluation of 3-month Dual Antiplatelet Therapy in Subjects at High Risk of Bleeding Undergoing Percutaneous Coronary Intervention With XIENCE.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03218787
• Other study ID #: 16-308
• Status: Completed
• Phase: N/A
• Start date: July 19, 2017
• Est. completion date: September 4, 2020

Study information

• Verified date: October 2021
• Source: Abbott Medical Devices
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

XIENCE 90 study is a prospective, single arm, multi-center, open label trial to evaluate the safety of 3-month dual antiplatelet therapy (DAPT) in subjects at high risk of bleeding (HBR) undergoing percutaneous coronary intervention (PCI) with the approved XIENCE family of coronary drug-eluting stents.

The XIENCE family stent systems include commercially approved XIENCE Xpedition Everolimus Eluting Coronary Stent System (EECSS), XIENCE Alpine EECSS, XIENCE PRO^X EECSS [rebrand of the XIENCE Xpedition Stent System and is only available outside of the United States (OUS)], XIENCE PRO^A EECSS (rebrand of the XIENCE Alpine Stent System and is only available OUS) and XIENCE Sierra EECSS of coronary drug-eluting stents.

Description:

A. Primary Objective:

To show non-inferiority of the primary endpoint of all death or all MI (modified ARC) from 3 to 12 months following XIENCE implantation in HBR subjects treated with 3-month DAPT compared to a historical control after propensity score adjustment.

B. Secondary Objective:

• To show superiority of the major secondary endpoint of major bleeding (Bleeding Academic Research Consortium [BARC] type 2-5) from 3 to 12 months following XIENCE implantation in HBR subjects treated with 3-month DAPT compared to a historical control after propensity score adjustment.

• To evaluate stent thrombosis (ARC definite/probable) from 3 to 12 months following XIENCE implantation in HBR subjects treated with 3-month DAPT against a performance goal (PG).

All registered subjects will be followed at 3, 6 and 12 months post index procedure.

The data collected from this study will be compared with the historical control of non-complex HBR subjects treated with standard DAPT duration of up to 12 months from the XIENCE V USA study, which is a US post-approval study to evaluate the safety of XIENCE V EECSS in "all-comer" population under real-world setting.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 2047
• Est. completion date: September 4, 2020
• Est. primary completion date: September 4, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Subject is considered at high risk for bleeding (HBR), defined as meeting one or more of the following criteria at the time of registration and in the opinion of the referring physician, the risk of major bleeding with > 3-month DAPT outweighs the benefit:

1. = 75 years of age.

2. Clinical indication for chronic (at least 6 months) or lifelong anticoagulation therapy.

3. History of major bleeding which required medical attention within 12 months of the index procedure.

4. History of stroke (ischemic or hemorrhagic).

5. Renal insufficiency (creatinine = 2.0 mg/dl) or failure (dialysis dependent).

6. Systemic conditions associated with an increased bleeding risk (e.g. hematological disorders, including a history of or current thrombocytopenia defined as a platelet count <100,000/mm^3, or any known coagulation disorder associated with increased bleeding risk).

7. Anemia with hemoglobin < 11g/dl.

2. Subject must be at least 18 years of age.

3. Subject or a legally authorized representative must provide written informed consent as approved by the Institutional Review Board (IRB)/Ethics Committee (EC) of the respective clinical site prior to any study related procedure.

4. Subject is willing to comply with all protocol requirements, including agreement to stop taking P2Y12 inhibitor at 3 months, if eligible per protocol.

5. Subject must agree not to participate in any other clinical trial for a period of one year following the index procedure.

Angiographic Inclusion Criteria

1. Up to three target lesions with a maximum of two target lesions per epicardial vessel. Note:

• The definition of epicardial vessels means left anterior descending coronary artery (LAD), left circumflex coronary artery (LCX) and right coronary artery (RCA) and their branches. For example, the patient must not have >2 lesions requiring treatment within both the LAD and a diagonal branch in total.

• If there are two target lesions within the same epicardial vessel, the two target lesions must be at least 15 mm apart per visual estimation; otherwise this is considered as a single target lesion.

2. Target lesion = 32 mm in length by visual estimation.

3. Target lesion must be located in a native coronary artery with visually estimated reference vessel diameter between 2.25 mm and 4.25 mm.

4. Exclusive use of XIENCE family of stent systems during the index procedure.

5. Target lesion has been treated successfully, which is defined as achievement of a final in-stent residual diameter stenosis of <20% with final TIMI-3 flow assessed by online quantitative angiography or visual estimation, with no residual dissection NHLBI grade = type B, and no transient or sustained angiographic complications (e.g., distal embolization, side branch closure), no chest pain lasting > 5 minutes, and no ST segment elevation > 0.5 mm or depression lasting > 5 minutes.

General Exclusion Criteria

1. Subject with an indication for the index procedure of acute ST-segment elevation MI (STEMI).

2. Subject has a known hypersensitivity or contraindication to aspirin, heparin/bivalirudin, P2Y12 inhibitors (clopidogrel/prasugrel/ticagrelor), everolimus, cobalt, chromium, nickel, tungsten, acrylic and fluoro polymers or contrast sensitivity that cannot be adequately pre-medicated.

3. Subject with implantation of another drug-eluting stent (other than XIENCE) within 9 months prior to index procedure.

4. Subject has a known left ventricular ejection fraction (LVEF) <30%.

5. Subject judged by physician as inappropriate for discontinuation from P2Y12 inhibitor use at 3 months, due to another condition requiring chronic P2Y12 inhibitor use.

6. Subject with planned surgery or procedure necessitating discontinuation of P2Y12 inhibitor within 3 months following index procedure.

7. Subject with a current medical condition with a life expectancy of less than 12 months.

8. Subject intends to participate in an investigational drug or device trial within 12 months following the index procedure.

9. Pregnant or nursing subjects and those who plan pregnancy in the period up to 1 year following index procedure. Female subjects of child-bearing potential must have a negative pregnancy test done within 7 days prior to the index procedure per site standard test.

Note: Female patients of childbearing potential should be instructed to use safe contraception (e.g., intrauterine devices, hormonal contraceptives: contraceptive pills, implants, transdermal patches, hormonal vaginal devices, injections with prolonged release.) It is accepted, in certain cases, to include subjects having a sterilised regular partner or subjects using a double barrier contraceptive method. However, this should be explicitly justified in special circumstances arising from the study design, product characteristics and/or study population

10. Subject is part of a vulnerable population, defined as subject whose willingness to volunteer in a clinical investigation could be unduly influenced by the expectation, whether justified or not, of benefits associated with participation or of retaliatory response from senior members of a hierarchy in case of refusal to participate. Examples of populations which may contain vulnerable subjects include: individuals with lack of or loss of autonomy due to immaturity or through mental disability, persons in nursing homes, children, impoverished persons, subjects in emergency situations, ethnic minority groups, homeless persons, nomads, refugees, and those incapable of giving informed consent. Other vulnerable subjects include, for example, members of a group with a hierarchical structure such as university students, subordinate hospital and laboratory personnel, employees of the sponsor, members of the armed forces, and persons kept in detention.

11. Subject is currently participating in another clinical trial that has not yet completed its primary endpoint.

Angiographic Exclusion Criteria

1. Target lesion is in a left main location.

2. Target lesion is located within an arterial or saphenous vein graft.

3. Target lesion is restenotic from a previous stent implantation.

4. Target lesion is a total occluded lesion (TIMI flow 0).

5. Target lesion contains thrombus as indicated in the angiographic images (per SYNTAX score thrombus definition).

6. Target lesion is implanted with overlapping stents, whether planned or for bailout.

Note: If there is more than one target lesion, all target lesions must satisfy the angiographic eligibility criteria. Non-target lesion (i.e., lesions that do not meet the angiographic criteria listed above) treatments are not allowed during the index procedure.

Related Conditions & MeSH terms

• Coronary Artery Lesions

Intervention

Device:
• XIENCE
Subjects who received XIENCE family stent systems will be included.

Drug:
• DAPT
3-month clear subjects who receive 3-month DAPT without interruption of either aspirin and/or P2Y12 receptor inhibitor for > 7 consecutive days. Subject who are "3-month clear" will discontinue P2Y12 inhibitor after 3-month visit, but continue taking aspirin through 12-month follow-up. Subjects who are not eligible for early P2Y12 inhibitor discontinuation will be treated per site standard of care.

Locations

Country	Name	City	State
United States	AnMed Health Clinical Research	Anderson	South Carolina
United States	JFK Medical Center	Atlantis	Florida
United States	Augusta Medical Center	Augusta	Georgia
United States	University Health, INC/University Cardiology Associates, LLC	Augusta	Georgia
United States	Rocky Mountain Regional VA Medical Center	Aurora	Colorado
United States	Heart Hospital of Austin	Austin	Texas
United States	MedStar Union Memorial Hospital	Baltimore	Maryland
United States	Eastern Maine Medical Center/One Northeast Drive	Bangor	Maine
United States	McLaren Bay Region	Bay City	Michigan
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Lahey Clinic/Lahey Hospital and Medical Center	Burlington	Massachusetts
United States	The University of Vermont Medical Center	Burlington	Vermont
United States	Our Lady of Lourdes/Cardiovascular Associates of the Delaware Valley (The Heart House)	Camden	New Jersey
United States	Holy Spirit Hospital	Camp Hill	Pennsylvania
United States	Charleston Area Medical Center Memorial Division	Charleston	West Virginia
United States	The Presbyterian Hospital (d/b/a Novant Health Heart and Vascular Institute) Novant Health Clinical Research	Charlotte	North Carolina
United States	Erlanger Medical Center	Chattanooga	Tennessee
United States	Clearwater Cardiovasular Consultants	Clearwater	Florida
United States	Morton Plant Mease Healthcare System	Clearwater	Florida
United States	University Hospitals Cleveland Medical Center	Cleveland	Ohio
United States	Boone Hospital Center (Missouri Cardiovascular Specialists)	Columbia	Missouri
United States	John Muir Health Concord	Concord	California
United States	Baylor Heart and Vascular Hospital	Dallas	Texas
United States	Atlanta Veterans Affairs Medical Center	Decatur	Georgia
United States	St John Hospital & Medical Center	Detroit	Michigan
United States	Doylestown Hospital	Doylestown	Pennsylvania
United States	St. Joseph's Hospital Health Center	East Syracuse	New York
United States	Elkhart General Hospital/Midwest Cardiology Research & Education Foundation	Elkhart	Indiana
United States	Englewood Hospital and Medical Center	Englewood	New Jersey
United States	UPMC Hamot/Medicor Associates, Inc.,	Erie	Pennsylvania
United States	Providence Regional Medical Center Everett	Everett	Washington
United States	Inova Fairfax Hospital/Inova Heart and Vascular Institute	Falls Church	Virginia
United States	New York - Presbyterian Queens Lang Research Center	Flushing	New York
United States	Mary Washington Hospital/Virginia Cardiovascular Consultants	Fredericksburg	Virginia
United States	Washington Hospital (Mission Cardiovascular Research Institute)	Fremont	California
United States	North Florida Regional / The Cardiac and Vascular Institute	Gainesville	Florida
United States	North Georgia Heart Foundation, Inc.	Gainesville	Georgia
United States	Genesys Regional Medical Center (Regional Cardiology Associates)	Grand Blanc	Michigan
United States	Harrisburg Hospital/Pinnacle Health Cardiovascular Institute, Inc.	Harrisburg	Pennsylvania
United States	Memorial Hermann-Hermann Hospital/UTHealth	Houston	Texas
United States	Huntsville Hospital (Heart Center Research LLC)	Huntsville	Alabama
United States	Franciscan Physician Network-Indiana Heart Physicians	Indianapolis	Indiana
United States	St. Vincent Heart Center of Indiana	Indianapolis	Indiana
United States	St Dominic-Jackson Memorial Hospital (Jackson Heart Clinic)	Jackson	Mississippi
United States	St. Vincent's Medical Center (St. Vincent's Healthcare)	Jacksonville	Florida
United States	Western Michigan University Homer Stryker M.D. School of Medicine	Kalamazoo	Michigan
United States	St. Luke's Hospital/Mid America Heart Institute	Kansas City	Missouri
United States	The University of Kansas Medical Center	Kansas City	Kansas
United States	Wellmont Holston Valley Medical Center	Kingsport	Tennessee
United States	Turkey Creek Medical Center (Knoxville HMA Cardiology, LLC)	Knoxville	Tennessee
United States	Scripps Memorial Hospital/Prebys Cardiovascular Institute	La Jolla	California
United States	St. Mary Medical Center	Langhorne	Pennsylvania
United States	University of Kentucky/Gill Heart and Vascular Institute	Lexington	Kentucky
United States	Bryan Local General Hospital (Bryan Medical Center East)	Lincoln	Nebraska
United States	Arkansas Heart Hospital	Little Rock	Arkansas
United States	Cedars-Sinai Medical Center	Los Angeles	California
United States	Baptist Health Louisville/Louisville Cardiology	Louisville	Kentucky
United States	Texas Tech University Health (University Medical Center)	Lubbock	Texas
United States	Baptist Memorial Hospital	Memphis	Tennessee
United States	MidMichigan Medical Center Midland	Midland	Michigan
United States	Abbott Northwestern Hospital (Minneapolis Heart Institute Foundation)	Minneapolis	Minnesota
United States	St. Patrick Hospital International Heart Institute of Montana Foundation	Missoula	Montana
United States	Morristown Medical Center	Morristown	New Jersey
United States	Centennial Medical Center (TriStar Centennial Medical Center)	Nashville	Tennessee
United States	Jersey Shore University Medical Center	Neptune	New Jersey
United States	Lenox Hill Hospital (Northwell)/ Feinstein Institute	New York	New York
United States	Mount Sinai Medical Center	New York	New York
United States	New York Presbyterian Hospital - Weill Cornell	New York	New York
United States	NYU Langone Health	New York	New York
United States	Integris Baptist Medical Center/Integris Cardiovascular Physicians, LLC	Oklahoma City	Oklahoma
United States	Penn Presbyterian Medical Center/Penn Heart and Vascular Pavilion,	Philadelphia	Pennsylvania
United States	Allegheny General Hospital	Pittsburgh	Pennsylvania
United States	UPMC	Pittsburgh	Pennsylvania
United States	Providence St. Vincent Medical Center	Portland	Oregon
United States	Rhode Island Hospital	Providence	Rhode Island
United States	NC Heart and Vascular Research	Raleigh	North Carolina
United States	University of California Davis Medical Center	Sacramento	California
United States	CentraCare	Saint Cloud	Minnesota
United States	Washington University School of Medicine Barnes Jewish Hospital	Saint Louis	Missouri
United States	Sharp Grossmont Hospital (La Mesa Cardiac Center)	San Diego	California
United States	Sharp Memorial Hospital / San Diego Cardiac Center	San Diego	California
United States	Santa Barbara Cottage Hospital/Sansum Clinic	Santa Barbara	California
United States	Scottsdale Healthcare Hospitals (d/b/a HonorHealth - HonorHealth Research Institute)	Scottsdale	Arizona
United States	Sanford Health	Sioux Falls	South Dakota
United States	Baystate Medical Center	Springfield	Massachusetts
United States	St. John's Hospital	Springfield	Illinois
United States	Stony Brook University Medical Center	Stony Brook	New York
United States	Tallahassee Memorial Hospital / Tallahassee Research Institute, Inc.	Tallahassee	Florida
United States	Cardiovascular Research Center, LLC (Mercy Health St. Vincent Medical Center LLC)	Toledo	Ohio
United States	Torrance Memorial Medical Center	Torrance	California
United States	Traverse Heart and Vascular Munson Medical Center	Traverse City	Michigan
United States	Hillcrest Medical Center (Oklahoma Heart Institute)	Tulsa	Oklahoma
United States	North Mississippi Medical Center (Cardiology Associates Research)	Tupelo	Mississippi
United States	East Texas Medical Center	Tyler	Texas
United States	Medstar Washington Hospital	Washington	District of Columbia
United States	Cardiovascular Research Institute of Kansas/Via Christi Regional Medical	Wichita	Kansas
United States	Kansas Heart Hospital (Cardiovascular Research Institute of Kansas)	Wichita	Kansas
United States	Wake Forest Baptist Medical Center (Wake Forest University Health Sciences)/Medical Center Boulevard	Winston-Salem	North Carolina
United States	St. Joseph Medical Center	Wyomissing	Pennsylvania
United States	St. Joseph Mercy Hospital (Michigan Heart)	Ypsilanti	Michigan

Sponsors (1)

Lead Sponsor	Collaborator
Abbott Medical Devices

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Composite Rate of All Death or All Myocardial Infarction (MI)(Modified Academic Research Consortium [ARC]), by Propensity Score Quintiles	All death: All deaths are considered cardiac unless an unequivocal non-cardiac cause can be established. Specifically, any unexpected death even in patients with coexisting potentially fatal non-cardiac disease should be classified as cardiac.; MI (Modified ARC): Patients present any of the following clinical or imaging evidence of ischemia: Clinical symptoms of ischemia; ECG changes indicative of new ischemia - new ST-T changes or new left bundle branch block, development of pathological Q waves; Imaging evidence of a new loss of viable myocardium or a new regional wall motion abnormality); AND confirmed with elevated cardiac biomarkers per ARC criteria: Periprocedural MI; Spontaneous MI: CK-MB > URL or Troponin > URL with baseline value < UR; The propensity score for each individual was calculated using a logistic regression model that included the study group as the outcome & the baseline demographic, clinical and procedural covariates as the predictors	From 3 to 12 months
Secondary	Percentage of Participants With Major Bleeding Rate by Bleeding Academic Research Consortium (BARC) Type 2-5, by Propensity Score Quintiles	Type 2: Any overt, actionable sign of hemorrhage; Type 3a: Overt bleeding plus Hb drop of 3 to < 5g/dL;Any transfusion with overt bleeding; Type 3b: Overt bleeding plus Hb drop = 5 g/dL;Cardiac tamponade;Bleeding requiring surgical intervention for control;Bleeding requiring IV vasoactive agents; Type 3c: ICH; Subcategories confirmed by autopsy/imaging/lumbar puncture;Intraocular bleed compromising vision; Type 4: CABG-related bleeding: Perioperative intracranial bleeding within 48h;Reoperation after closure of sternotomy for the purpose of controlling bleeding;Transfusion of = 5 U whole blood or packed RBC within 48h;Chest tube output = 2L within 24h; Type 5: Fatal bleeding; The propensity score for each individual was calculated using a logistic regression model that included the study group as the outcome & the baseline demographic, clinical and procedural covariates as the predictors.	From 3 to 12 months
Secondary	Number of Participants With Stent Thrombosis (ARC Definite/Probable)	Definite stent thrombosis: Definite stent thrombosis is considered to have occurred by either angiographic or pathologic confirmation.; Probable stent thrombosis: Clinical definition of probable stent thrombosis is considered to have occurred after intracoronary stenting in the following cases: Any unexplained death within the first 30 days; Irrespective of the time after the index procedure, any MI that is related to documented acute ischemia in the territory of the implanted stent without angiographic confirmation of stent thrombosis and in the absence of any other obvious cause	From 3 to 12 months
Secondary	Number of Participants With All Death, Cardiac Death, Vascular Death, Non-cardiovascular Death	All Death: All deaths are considered cardiac unless an unequivocal non-cardiac cause can be established. Specifically, any unexpected death even in patients with coexisting potentially fatal non-cardiac disease (e.g. cancer, infection) should be classified as cardiac.; Cardiac death: Any death due to proximate cardiac cause (e.g. MI, low-output failure, fatal arrhythmia), unwitnessed death and death of unknown cause, all procedure related deaths including those related to concomitant treatment.; Vascular death: Death due to non-coronary vascular causes such as cerebrovascular disease, pulmonary embolism, ruptured aortic aneurysm, dissecting aneurysm, or other vascular cause.; Non-cardiovascular death: Any death not covered by the above definitions such as death caused by infection, malignancy, sepsis, pulmonary causes, accident, suicide or trauma.	From 3 to 12 months
Secondary	Number of Participants With All Myocardial Infarction (MI) and MI Attributed to Target Vessel (TV-MI, Modified ARC)	All Myocardial Infarction (Modified ARC): Patients present any of the following clinical or imaging evidence of ischemia: Clinical symptoms of ischemia; ECG changes indicative of new ischemia - new ST-T changes or new left bundle branch block (LBBB), development of pathological Q waves; Imaging evidence of a new loss of viable myocardium or a new regional wall motion abnormality); AND confirmed with elevated cardiac biomarkers per ARC criteria: Periprocedural MI: Within 48h after PCI: CK-MB >3 x URL or Troponin > 3 x URL with baseline value < URL; Within 72h after CABG: CK-MB >5 x URL or Troponin > 5 x URL with baseline value < URL; Spontaneous MI (> 48h following PCI, > 72h following CABG): CK-MB > URL or Troponin > URL with baseline value < URL; TV-MI: All infarcts that cannot be clearly attributed to a vessel other than the target vessel will be considered related to the target vessel.	From 3 to 12 months
Secondary	Number of Participants With Composite of Cardiac Death or MI (Modified ARC)	Cardiac death: Any death due to proximate cardiac cause (e.g. MI, low-output failure, fatal arrhythmia), unwitnessed death and death of unknown cause, all procedure related deaths including those related to concomitant treatment.; MI (Modified ARC): Patients present any of the following clinical or imaging evidence of ischemia: Clinical symptoms of ischemia; ECG changes indicative of new ischemia - new ST-T changes or new left bundle branch block (LBBB), development of pathological Q waves; Imaging evidence of a new loss of viable myocardium or a new regional wall motion abnormality); AND confirmed with elevated cardiac biomarkers per ARC criteria: Periprocedural MI: Within 48h after PCI: CK-MB >3 x URL or Troponin > 3 x URL with baseline value < URL; Within 72h after CABG: CK-MB >5 x URL or Troponin > 5 x URL with baseline value < URL; Spontaneous MI (> 48h following PCI, > 72h following CABG): CK-MB > URL or Troponin > URL with baseline value < URL	From 3 to 12 months
Secondary	Number of Participants With All Stroke, Ischemic Stroke and Hemorrhagic Stroke	An acute symptomatic episode of neurological dysfunction attributed to a vascular cause lasting more than 24 hours or lasting 24 hours or less with a brain imaging study or autopsy showing new infarction.; Ischemic Stroke: An acute symptomatic episode of focal cerebral, spinal, or retinal dysfunction caused by an infarction of central nervous system tissue.; Hemorrhagic Stroke: An acute symptomatic episode of focal or global cerebral or spinal dysfunction caused by a non-traumatic intraparenchymal, intraventricular, or subarachnoid hemorrhage.; Undetermined Stroke: A stroke with insufficient information to allow categorization as ischemic or hemorrhagic.; Pharmacologic, i.e., thrombolytic drug administration, or Non-pharmacologic, i.e., neurointerventional procedure (e.g., intracranial angioplasty)	From 3 to 12 months
Secondary	Number of Participants With Clinically-indicated Target Lesion Revascularization (CI-TLR)	Target Lesion Revascularization (TLR) is defined as any repeat percutaneous intervention of the target lesion or bypass surgery of the target vessel performed for restenosis or other complication of the target lesion. All TLR should be classified prospectively as clinically indicated [CI] or not clinically indicated by the investigator prior to repeat angiography.; Clinically Indicated [CI] Revascularization: A revascularization is considered clinically indicated if angiography at follow-up shows a percent diameter stenosis = 50% and if one of the following occurs: A positive history of recurrent angina pectoris, presumably related to the target vessel; Objective signs of ischemia at rest (ECG changes) or during exercise test (or equivalent), presumably related to the target vessel; Abnormal results of any invasive functional diagnostic test; A TLR/TVR with a diameter stenosis =70% in the absence of the above mentioned ischemic signs or symptoms.	From 3 to 12 months
Secondary	Number of Participants With Clinically-indicated Target Vessel Revascularization (CI-TVR)	TVR is defined as any repeat percutaneous intervention or surgical bypass of any segment of the target vessel. The target vessel is defined as the entire major coronary vessel proximal and distal to the target lesion which includes upstream and downstream branches and the target lesion itself.; A revascularization is considered clinically indicated if angiography at follow-up shows a percent diameter stenosis = 50% and if one of the following occurs: A positive history of recurrent angina pectoris, presumably related to the target vessel; Objective signs of ischemia at rest (ECG changes) or during exercise test (or equivalent), presumably related to the target vessel; Abnormal results of any invasive functional diagnostic test (e.g., Doppler flow velocity reserve, fractional flow reserve); A TVR with a diameter stenosis =70% in the absence of the above mentioned ischemic signs or symptoms.	From 3 to 12 months
Secondary	Number of Participants With Target Lesion Failure (TLF, Composite of Cardiac Death, TV-MI and CI-TLR)	TLF is defined as a composite of all cardiac death, myocardial infarction attributed to target vessel or clinically-indicated TLR.	From 3 to 12 months
Secondary	Number of Participants With Target Vessel Failure (TVF, Composite of Cardiac Death, TV-MI and CI-TVR)	TVF is defined as a composite of cardiac death, MI attributed to target vessel, clinically-indicated TLR, or clinically-indicated TVR, non-TLR.	From 3 to 12 months
Secondary	Number of Participants With Major Bleeding Defined by the Bleeding Academic Research Consortium (BARC) Type 3-5	Bleeding per Bleeding Academic Research Consortium (BARC) adjudicated definitions are as follows: Type 3a: Overt bleeding plus Hemoglobin(Hb) drop of 3 to < 5 g/dL; Any transfusion with overt bleeding; Type 3b: Overt bleeding plus Hb drop = 5 g/dL; Cardiac tamponade; Bleeding requiring surgical intervention for control; Bleeding requiring IV vasoactive agents; Type 3c: Intracranial hemorrhage;Subcategories confirmed by autopsy or imaging or lumbar puncture; Intraocular bleed compromising vision; Type 4: CABG-related bleeding: Perioperative intracranial bleeding within 48 h; Reoperation after closure of sternotomy for the purpose of controlling bleeding; Transfusion of = 5 U whole blood or packed red blood cells within a 48-h period; Chest tube output = 2L within a 24-h period; Type 5: Fatal bleeding; Type 5a: Probable fatal bleeding; no autopsy or imaging confirmation but clinically suspicious; Type 5b: Definite fatal bleeding;overt bleeding or autopsy or imaging confirmation	From 3 to 12 months