Clinical trial NCT03218787: XIENCE 90: A Safety Evaluation of 3-month DAPT After XIENCE Implantation for HBR Patients.
Official title: A Safety Evaluation of 3-month Dual Antiplatelet Therapy in Subjects at High Risk of Bleeding Undergoing Percutaneous Coronary Intervention With XIENCE.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Coronary Artery Lesions
Keywords: Coronary Artery Lesions
XIENCE
Dual Antiplatelet Therapy (DAPT)
Reduced DAPT
Risk of bleeding
Drug-eluting stents
Lead sponsor: Abbott Medical Devices
Sponsor class: INDUSTRY
First posted: 2017-07-17
Enrollment: 2047
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of Participants With Composite Rate of All Death or All Myocardial Infarction (MI)(Modified Academic Research Consortium [ARC]), by Propensity Score Quintiles
timeFrame: From 3 to 12 months
Secondary outcomes:
measure: Percentage of Participants With Major Bleeding Rate by Bleeding Academic Research Consortium (BARC) Type 2-5, by Propensity Score Quintiles
timeFrame: From 3 to 12 months
measure: Number of Participants With Stent Thrombosis (ARC Definite/Probable)
timeFrame: From 3 to 12 months
measure: Number of Participants With All Death, Cardiac Death, Vascular Death, Non-cardiovascular Death
timeFrame: From 3 to 12 months
measure: Number of Participants With All Myocardial Infarction (MI) and MI Attributed to Target Vessel (TV-MI, Modified ARC)
timeFrame: From 3 to 12 months
measure: Number of Participants With Composite of Cardiac Death or MI (Modified ARC)
timeFrame: From 3 to 12 months
measure: Number of Participants With All Stroke, Ischemic Stroke and Hemorrhagic Stroke
timeFrame: From 3 to 12 months
measure: Number of Participants With Clinically-indicated Target Lesion Revascularization (CI-TLR)
timeFrame: From 3 to 12 months
measure: Number of Participants With Clinically-indicated Target Vessel Revascularization (CI-TVR)
timeFrame: From 3 to 12 months
measure: Number of Participants With Target Lesion Failure (TLF, Composite of Cardiac Death, TV-MI and CI-TLR)
timeFrame: From 3 to 12 months
measure: Number of Participants With Target Vessel Failure (TVF, Composite of Cardiac Death, TV-MI and CI-TVR)
timeFrame: From 3 to 12 months
measure: Number of Participants With Major Bleeding Defined by the Bleeding Academic Research Consortium (BARC) Type 3-5
timeFrame: From 3 to 12 months
Other outcomes:
Locations:
city: Huntsville
country: United States
facility: Huntsville Hospital (Heart Center Research LLC)
state: Alabama
city: Scottsdale
country: United States
facility: Scottsdale Healthcare Hospitals (d/b/a HonorHealth - HonorHealth Research Institute)
state: Arizona
city: Little Rock
country: United States
facility: Arkansas Heart Hospital
state: Arkansas
city: Concord
country: United States
facility: John Muir Health Concord
state: California
city: Fremont
country: United States
facility: Washington Hospital (Mission Cardiovascular Research Institute)
state: California
city: La Jolla
country: United States
facility: Scripps Memorial Hospital/Prebys Cardiovascular Institute
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Sacramento
country: United States
facility: University of California Davis Medical Center
state: California
city: San Diego
country: United States
facility: Sharp Grossmont Hospital (La Mesa Cardiac Center)
state: California
city: San Diego
country: United States
facility: Sharp Memorial Hospital / San Diego Cardiac Center
state: California
city: Santa Barbara
country: United States
facility: Santa Barbara Cottage Hospital/Sansum Clinic
state: California
city: Torrance
country: United States
facility: Torrance Memorial Medical Center
state: California
city: Aurora
country: United States
facility: Rocky Mountain Regional VA Medical Center
state: Colorado
city: Washington
country: United States
facility: Medstar Washington Hospital
state: District of Columbia
city: Atlantis
country: United States
facility: JFK Medical Center
state: Florida
city: Clearwater
country: United States
facility: Clearwater Cardiovasular Consultants
state: Florida
city: Clearwater
country: United States
facility: Morton Plant Mease Healthcare System
state: Florida
city: Gainesville
country: United States
facility: North Florida Regional / The Cardiac and Vascular Institute
state: Florida
city: Jacksonville
country: United States
facility: St. Vincent's Medical Center (St. Vincent's Healthcare)
state: Florida
city: Tallahassee
country: United States
facility: Tallahassee Memorial Hospital / Tallahassee Research Institute, Inc.
state: Florida
city: Augusta
country: United States
facility: University Health, INC/University Cardiology Associates, LLC
state: Georgia
city: Augusta
country: United States
facility: Augusta Medical Center
state: Georgia
city: Decatur
country: United States
facility: Atlanta Veterans Affairs Medical Center
state: Georgia
city: Gainesville
country: United States
facility: North Georgia Heart Foundation, Inc.
state: Georgia
city: Springfield
country: United States
facility: St. John's Hospital
state: Illinois
city: Elkhart
country: United States
facility: Elkhart General Hospital/Midwest Cardiology Research & Education Foundation
state: Indiana
city: Indianapolis
country: United States
facility: Franciscan Physician Network-Indiana Heart Physicians
state: Indiana
city: Indianapolis
country: United States
facility: St. Vincent Heart Center of Indiana
state: Indiana
city: Kansas City
country: United States
facility: The University of Kansas Medical Center
state: Kansas
city: Wichita
country: United States
facility: Cardiovascular Research Institute of Kansas/Via Christi Regional Medical
state: Kansas
city: Wichita
country: United States
facility: Kansas Heart Hospital (Cardiovascular Research Institute of Kansas)
state: Kansas
city: Lexington
country: United States
facility: University of Kentucky/Gill Heart and Vascular Institute
state: Kentucky
city: Louisville
country: United States
facility: Baptist Health Louisville/Louisville Cardiology
state: Kentucky
city: Bangor
country: United States
facility: Eastern Maine Medical Center/One Northeast Drive
state: Maine
city: Baltimore
country: United States
facility: MedStar Union Memorial Hospital
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Burlington
country: United States
facility: Lahey Clinic/Lahey Hospital and Medical Center
state: Massachusetts
city: Springfield
country: United States
facility: Baystate Medical Center
state: Massachusetts
city: Bay City
country: United States
facility: McLaren Bay Region
state: Michigan
city: Detroit
country: United States
facility: St John Hospital & Medical Center
state: Michigan
city: Grand Blanc
country: United States
facility: Genesys Regional Medical Center (Regional Cardiology Associates)
state: Michigan
city: Kalamazoo
country: United States
facility: Western Michigan University Homer Stryker M.D. School of Medicine
state: Michigan
city: Midland
country: United States
facility: MidMichigan Medical Center Midland
state: Michigan
city: Traverse City
country: United States
facility: Traverse Heart and Vascular Munson Medical Center
state: Michigan
city: Ypsilanti
country: United States
facility: St. Joseph Mercy Hospital (Michigan Heart)
state: Michigan
city: Minneapolis
country: United States
facility: Abbott Northwestern Hospital (Minneapolis Heart Institute Foundation)
state: Minnesota
city: Saint Cloud
country: United States
facility: CentraCare
state: Minnesota
city: Jackson
country: United States
facility: St Dominic-Jackson Memorial Hospital (Jackson Heart Clinic)
state: Mississippi
city: Tupelo
country: United States
facility: North Mississippi Medical Center (Cardiology Associates Research)
state: Mississippi
city: Columbia
country: United States
facility: Boone Hospital Center (Missouri Cardiovascular Specialists)
state: Missouri
city: Kansas City
country: United States
facility: St. Luke's Hospital/Mid America Heart Institute
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine Barnes Jewish Hospital
state: Missouri
city: Missoula
country: United States
facility: St. Patrick Hospital International Heart Institute of Montana Foundation
state: Montana
city: Lincoln
country: United States
facility: Bryan Local General Hospital (Bryan Medical Center East)
state: Nebraska
city: Camden
country: United States
facility: Our Lady of Lourdes/Cardiovascular Associates of the Delaware Valley (The Heart House)
state: New Jersey
city: Englewood
country: United States
facility: Englewood Hospital and Medical Center
state: New Jersey
city: Morristown
country: United States
facility: Morristown Medical Center
state: New Jersey
city: Neptune
country: United States
facility: Jersey Shore University Medical Center
state: New Jersey
city: East Syracuse
country: United States
facility: St. Joseph's Hospital Health Center
state: New York
city: Flushing
country: United States
facility: New York - Presbyterian Queens Lang Research Center
state: New York
city: New York
country: United States
facility: NYU Langone Health
state: New York
city: New York
country: United States
facility: Mount Sinai Medical Center
state: New York
city: New York
country: United States
facility: New York Presbyterian Hospital - Weill Cornell
state: New York
city: New York
country: United States
facility: Lenox Hill Hospital (Northwell)/ Feinstein Institute
state: New York
city: Stony Brook
country: United States
facility: Stony Brook University Medical Center
state: New York
city: Charlotte
country: United States
facility: The Presbyterian Hospital (d/b/a Novant Health Heart and Vascular Institute) Novant Health Clinical Research
state: North Carolina
city: Raleigh
country: United States
facility: NC Heart and Vascular Research
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Medical Center (Wake Forest University Health Sciences)/Medical Center Boulevard
state: North Carolina
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center
state: Ohio
city: Toledo
country: United States
facility: Cardiovascular Research Center, LLC (Mercy Health St. Vincent Medical Center LLC)
state: Ohio
city: Oklahoma City
country: United States
facility: Integris Baptist Medical Center/Integris Cardiovascular Physicians, LLC
state: Oklahoma
city: Tulsa
country: United States
facility: Hillcrest Medical Center (Oklahoma Heart Institute)
state: Oklahoma
city: Portland
country: United States
facility: Providence St. Vincent Medical Center
state: Oregon
city: Camp Hill
country: United States
facility: Holy Spirit Hospital
state: Pennsylvania
city: Doylestown
country: United States
facility: Doylestown Hospital
state: Pennsylvania
city: Erie
country: United States
facility: UPMC Hamot/Medicor Associates, Inc.,
state: Pennsylvania
city: Harrisburg
country: United States
facility: Harrisburg Hospital/Pinnacle Health Cardiovascular Institute, Inc.
state: Pennsylvania
city: Langhorne
country: United States
facility: St. Mary Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Penn Presbyterian Medical Center/Penn Heart and Vascular Pavilion,
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Allegheny General Hospital
state: Pennsylvania
city: Wyomissing
country: United States
facility: St. Joseph Medical Center
state: Pennsylvania
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Anderson
country: United States
facility: AnMed Health Clinical Research
state: South Carolina
city: Sioux Falls
country: United States
facility: Sanford Health
state: South Dakota
city: Chattanooga
country: United States
facility: Erlanger Medical Center
state: Tennessee
city: Kingsport
country: United States
facility: Wellmont Holston Valley Medical Center
state: Tennessee
city: Knoxville
country: United States
facility: Turkey Creek Medical Center (Knoxville HMA Cardiology, LLC)
state: Tennessee
city: Memphis
country: United States
facility: Baptist Memorial Hospital
state: Tennessee
city: Nashville
country: United States
facility: Centennial Medical Center (TriStar Centennial Medical Center)
state: Tennessee
city: Austin
country: United States
facility: Heart Hospital of Austin
state: Texas
city: Dallas
country: United States
facility: Baylor Heart and Vascular Hospital
state: Texas
city: Houston
country: United States
facility: Memorial Hermann-Hermann Hospital/UTHealth
state: Texas
city: Lubbock
country: United States
facility: Texas Tech University Health (University Medical Center)
state: Texas
city: Tyler
country: United States
facility: East Texas Medical Center
state: Texas
city: Burlington
country: United States
facility: The University of Vermont Medical Center
state: Vermont
city: Falls Church
country: United States
facility: Inova Fairfax Hospital/Inova Heart and Vascular Institute
state: Virginia
city: Fredericksburg
country: United States
facility: Mary Washington Hospital/Virginia Cardiovascular Consultants
state: Virginia
city: Everett
country: United States
facility: Providence Regional Medical Center Everett
state: Washington
city: Charleston
country: United States
facility: Charleston Area Medical Center Memorial Division
state: West Virginia
Study officials:
affiliation: Abbott Medical Devices
name: Roxana Mehran
role: PRINCIPAL_INVESTIGATOR
References:
citation: Valgimigli M, Cao D, Angiolillo DJ, Bangalore S, Bhatt DL, Ge J, Hermiller J, Makkar RR, Neumann FJ, Saito S, Picon H, Toelg R, Maksoud A, Chehab BM, Choi JW, Campo G, De la Torre Hernandez JM, Kunadian V, Sardella G, Thiele H, Varenne O, Vranckx P, Windecker S, Zhou Y, Krucoff MW, Ruster K, Zheng Y, Mehran R; XIENCE 90 and XIENCE 28 Investigators. Duration of Dual Antiplatelet Therapy for Patients at High Bleeding Risk Undergoing PCI. J Am Coll Cardiol. 2021 Nov 23;78(21):2060-2072. doi: 10.1016/j.jacc.2021.08.074.
citation: Valgimigli M, Cao D, Makkar RR, Bangalore S, Bhatt DL, Angiolillo DJ, Saito S, Ge J, Neumann FJ, Hermiller J, Picon H, Toelg R, Maksoud A, Chehab BM, Wang LJ, Wang J, Mehran R. Design and rationale of the XIENCE short DAPT clinical program: An assessment of the safety of 3-month and 1-month DAPT in patients at high bleeding risk undergoing PCI with an everolimus-eluting stent. Am Heart J. 2021 Jan;231:147-156. doi: 10.1016/j.ahj.2020.09.019. Epub 2020 Oct 6.