Clinical trial NCT03815175: XIENCE 28 USA Study
Official title: XIENCE 28 USA Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Bleeding Disorder
Ischemic Stroke
Hemorrhagic Stroke
Hematological Diseases
Thrombocytopenia
Coagulation Disorder
Anemia
Renal Insufficiency
Coronary Artery Disease
Keywords: High Bleeding Risk (HBR)
Dual antiplatelet therapy (DAPT)
Drug eluting stent (DES)
XIENCE
Percutaneous coronary intervention (PCI)
Coronary Artery Disease
Lead sponsor: Abbott Medical Devices
Sponsor class: INDUSTRY
First posted: 2019-01-24
Enrollment: 1605
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The XIENCE 28 USA Study is prospective, single arm, multi-center, open label, non-randomized trial to evaluate safety of 1-month (as short as 28 days) dual antiplatelet therapy (DAPT) in subjects at high risk of bleeding (HBR) undergoing percutaneous coronary intervention (PCI) with the approved XIENCE family (XIENCE Xpedition Everolimus Eluting Coronary Stent System \[EECSS\], XIENCE Alpine EECSS and XIENCE Sierra EECSS) of coronary drug-eluting stents.

Detailed description: The XIENCE 28 USA Study will evaluate the safety of 1-month DAPT following XIENCE implantation in HBR patients. A minimum of 640 to a maximum of 800 subjects will be registered from approximately 50 sites in the United States and Canada. Subject registration is capped at 75 per site. Eligibility of P2Y12 receptor inhibitor discontinuation will be assessed at 1-month follow-up. Subjects who are free from myocardial infarction (MI), repeat coronary revascularization, stroke, or stent thrombosis (ARC definite/probable) within 1 month (prior to 1-month visit but at least 28 days) after stenting AND have been compliant with 1-month DAPT without interruption of either aspirin and/or P2Y12 receptor inhibitor for \> 7 consecutive days are considered as "1-month clear", and will discontinue P2Y12 receptor inhibitor as early as 28 days and continued with aspirin monotherapy through 12-month follow-up.

All registered subjects will be followed at 1, 3, 6 and 12 months post index procedure. The data collected from the XIENCE 28 USA Study will be pooled with the data from the XIENCE 28 Global Study (Protocol # ABT-CIP-10235) to compare 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.

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 \> 1-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/mm3, 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 must provide written informed consent as approved by the Institutional Review Board (IRB) of the respective clinical site prior to any trial related procedure.
4. Subject is willing to comply with all protocol requirements, including agreement to stop taking P2Y12 inhibitor at 1 month, 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, except for cases where subject is transferred to the XIENCE 90 study after the 1-month visit assessment

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 subject 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 must be located in a native coronary artery with visually estimated reference vessel diameter between 2.25 mm and 4.25 mm.
3. Exclusive use of XIENCE family of stent systems during the index procedure.
4. 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 \> 0.5mm or depression lasting \> 5 minutes.

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 12 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 1 month, due to another condition requiring chronic P2Y12 inhibitor use.
6. Subject with planned surgery or procedure necessitating discontinuation of P2Y12 inhibitor within 1 month 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. Transferring to the XIENCE 90 study will not be an exclusion criterion.
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.
10. Presence of other anatomic or comorbid conditions, or other medical, social, or psychological conditions that, in the investigator's opinion, could limit the subject's ability to participate in the clinical investigation or to comply with follow-up requirements, or impact the scientific soundness of the clinical investigation results.
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 chronic total occlusion (CTO, defined as lesion with TIMI flow 0 for at least 3 months).
5. Target lesion is implanted with overlapping stents, whether planned or for bailout.

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 Quintile
timeFrame: From 1 to 6 months
measure: Percentage of Participants With Composite Rate of All Death or All Myocardial Infarction (Modified ARC), by Propensity Score Quintile
timeFrame: From 6 to 12 months
measure: Percentage of Participants With Composite Rate of All Death or All Myocardial Infarction (Modified ARC), by Propensity Score Quintile
timeFrame: From 1 to 12 months
Secondary outcomes:
measure: Percentage of Participants With Major Bleeding Rate (Bleeding Academic Research Consortium [BARC] Type 2-5), by Propensity Score Quintiles
timeFrame: From 1 to 6 months
measure: Percentage of Participants With Major Bleeding Rate (BARC Type 2-5), by Propensity Score Quintiles
timeFrame: From 6 to 12 months
measure: Percentage of Participants With Major Bleeding Rate (BARC Type 2-5), by Propensity Score Quintiles
timeFrame: From 1 to 12 months
measure: Number of Participants With Stent Thrombosis (ARC Definite/Probable, ARC Definite)
timeFrame: From 1 to 6 months
measure: Number of Participants With Stent Thrombosis (ARC Definite/Probable, ARC Definite)
timeFrame: From 6 to 12 months
measure: Number of Participants With Stent Thrombosis (ARC Definite/Probable, ARC Definite)
timeFrame: From 1 to 12 months
measure: Number of All Death (Cardiac Death, Vascular Death, Non-cardiovascular Death)
timeFrame: From 1 to 6 months
measure: Number of All Death (Cardiac Death, Vascular Death, Non-cardiovascular Death)
timeFrame: From 6 to 12 months
measure: Number of All Death (Cardiac Death, Vascular Death, Non-cardiovascular Death)
timeFrame: From 1 to 12 months
measure: Number of Participants With All Myocardial Infarction (MI) and MI Attributed to Target Vessel (TV-MI, Modified ARC)
timeFrame: From 1 to 6 months
measure: Number of Participants With All MI and MI Attributed to Target Vessel (TV-MI, Modified ARC)
timeFrame: From 6 to 12 months
measure: Number of Participants With All MI and MI Attributed to Target Vessel (TV-MI, Modified ARC)
timeFrame: From 1 to 12 months
measure: Number of Participants With Composite of Cardiac Death or MI (Modified ARC)
timeFrame: From 1 to 6 months
measure: Number of Participants With Composite of Cardiac Death or MI (Modified ARC)
timeFrame: From 6 to 12 months
measure: Number of Participants With Composite of Cardiac Death or MI (Modified ARC)
timeFrame: From 1 to 12 months
measure: Number of Participants With Composite of All Death or All MI (Modified ARC)
timeFrame: From 1 to 6 months
measure: Number of Participants With Composite of All Death or All MI (Modified ARC)
timeFrame: From 6 to 12 months
measure: Number of Participants With Composite of All Death or All MI (Modified ARC)
timeFrame: From 1 to 12 months
measure: Number of Participants With All Stroke (Ischemic Stroke and Hemorrhagic Stroke)
timeFrame: From 1 to 6 months
measure: Number of Participants With All Stroke (Ischemic Stroke and Hemorrhagic Stroke)
timeFrame: From 6 to 12 months
measure: Number of Participants With All Stroke (Ischemic Stroke and Hemorrhagic Stroke)
timeFrame: From 1 to 12 months
measure: Number of Participants With Clinically-indicated Target Lesion Revascularization (CI-TLR)
timeFrame: From 1 to 6 months
measure: Number of Participants With CI-TLR
timeFrame: From 6 to 12 months
measure: Number of Participants With CI-TLR
timeFrame: From 1 to 12 months
measure: Number of Participants With Clinically-indicated Target Vessel Revascularization (CI-TVR)
timeFrame: From 1 to 6 months
measure: Number of Participants With CI-TVR
timeFrame: From 6 to 12 months
measure: Number of Participants With CI-TVR
timeFrame: From 1 to 12 months
measure: Number of Participants With Target Lesion Failure (TLF, Composite of Cardiac Death, TV-MI and CI-TLR)
timeFrame: From 1 to 6 months
measure: Number of Participants With Target Lesion Failure (TLF, Composite of Cardiac Death, TV-MI and CI-TLR)
timeFrame: From 6 to 12 months
measure: Number of Participants With Target Lesion Failure (TLF, Composite of Cardiac Death, TV-MI and CI-TLR)
timeFrame: From 1 to 12 months
measure: Number of Participants With Target Vessel Failure (TVF, Composite of Cardiac Death, TV-MI and CI-TVR)
timeFrame: From 1 to 6 months
measure: Number of Participants With Target Vessel Failure (TVF, Composite of Cardiac Death, TV-MI and CI-TVR)
timeFrame: From 6 to 12 months
measure: Number of Participants With Target Vessel Failure (TVF, Composite of Cardiac Death, TV-MI and CI-TVR)
timeFrame: From 1 to 12 months
measure: Number of Participants With Major Bleeding Defined by the Bleeding Academic Research Consortium (BARC) Type 3-5
timeFrame: From 1 to 6 months
measure: Number of Participants With Major Bleeding Defined by the Bleeding Academic Research Consortium (BARC) Type 3-5
timeFrame: From 6 to 12 months
measure: Number of Participants With Major Bleeding Defined by the Bleeding Academic Research Consortium (BARC) Type 3-5
timeFrame: From 1 to 12 months
Other outcomes:
Locations:
city: Huntsville
country: United States
facility: Heart Center Research, LLC
state: Alabama
city: Phoenix
country: United States
facility: Phoenix Cardiovascular Research Group
state: Arizona
city: Scottsdale
country: United States
facility: Scottsdale Healthcare Shea
state: Arizona
city: Jonesboro
country: United States
facility: NEA Baptist Clinic
state: Arkansas
city: Little Rock
country: United States
facility: Arkansas Heart Hospital
state: Arkansas
city: Fremont
country: United States
facility: Mission Cardiovascular Research Institute
state: California
city: La Jolla
country: United States
facility: Scripps Memorial Hospital - La Jolla
state: California
city: Pasadena
country: United States
facility: Huntington Memorial Hospital
state: California
city: Santa Barbara
country: United States
facility: Santa Barbara Cottage Hospital
state: California
city: Santa Clara
country: United States
facility: Kaiser Permanente - Santa Clara
state: California
city: Norwalk
country: United States
facility: Cardiology Associates of Fairfield County, PC
state: Connecticut
city: Washington
country: United States
facility: Washington Hospital Center
state: District of Columbia
city: Clearwater
country: United States
facility: Clearwater Cardiovascular Consultants
state: Florida
city: Clearwater
country: United States
facility: Morton Plant Hospital
state: Florida
city: Tallahassee
country: United States
facility: Tallahassee Research Institute
state: Florida
city: Gainesville
country: United States
facility: Northeast Georgia Medical Center
state: Georgia
city: Rome
country: United States
facility: Redmond Regional Medical Center
state: Georgia
city: Wichita
country: United States
facility: Via Christi Regional Medical Center - St. Francis Campus
state: Kansas
city: Wichita
country: United States
facility: Cardiovascular Research Institute of Kansas
state: Kansas
city: Bangor
country: United States
facility: Eastern Maine Medical Center
state: Maine
city: Baltimore
country: United States
facility: Union Memorial Hospital
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth Isreal Deaconess Medical Center
state: Massachusetts
city: Auburn Hills
country: United States
facility: McLaren Health Care Corporation
state: Michigan
city: Traverse City
country: United States
facility: Munson Medical Center
state: Michigan
city: Minneapolis
country: United States
facility: Minneapolis Heart Institute
state: Minnesota
city: Jackson
country: United States
facility: Jackson Heart Clinic
state: Mississippi
city: Columbia
country: United States
facility: Missouri Heart Center
state: Missouri
city: Neptune
country: United States
facility: Jersey Shore University Medical Center
state: New Jersey
city: New York
country: United States
facility: Mount Sinai Hospital
state: New York
city: New York
country: United States
facility: Lenox Hill Hospital
state: New York
city: Syracuse
country: United States
facility: St. Joseph's Hospital Health Center
state: New York
city: Charlotte
country: United States
facility: Novant Health Heart and Vascular Research Institute
state: North Carolina
city: Greensboro
country: United States
facility: Cone Health Medical Group Heartcare
state: North Carolina
city: Raleigh
country: United States
facility: NC Heart & Vascular Research
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University Medical Center Clinical Sciences
state: North Carolina
city: Kettering
country: United States
facility: Kettering Medical Center
state: Ohio
city: Toledo
country: United States
facility: St. Vincent Mercy Medical Center
state: Ohio
city: Erie
country: United States
facility: UPMC Hamot
state: Pennsylvania
city: Harrisburg
country: United States
facility: Pinnacle Health System
state: Pennsylvania
city: Philadelphia
country: United States
facility: Presbyterian Medical Center (PA)
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Allegheny General Hospital
state: Pennsylvania
city: Reading
country: United States
facility: St. Joseph Medical Center
state: Pennsylvania
city: Anderson
country: United States
facility: Anmed Health
state: South Carolina
city: Sioux Falls
country: United States
facility: Sanford USD Medical Center
state: South Dakota
city: Knoxville
country: United States
facility: East Tennessee Heart Consultants
state: Tennessee
city: Nashville
country: United States
facility: Centennial Medical Center
state: Tennessee
city: Austin
country: United States
facility: Austin Heart
state: Texas
city: Dallas
country: United States
facility: Baylor Scott and White Heart and Vascular Hospital
state: Texas
city: New Braunfels
country: United States
facility: Mission Research Institute
state: Texas
city: Richardson
country: United States
facility: HeartPlace Methodist Richardson
state: Texas
city: Tyler
country: United States
facility: East Texas Medical Center
state: Texas
city: Fredericksburg
country: United States
facility: Mary Washington Hospital
state: Virginia
city: Charleston
country: United States
facility: Charleston Area Medical Center
state: West Virginia
city: Linz
country: Austria
facility: Kepler Universitätsklinikum GmbH
state: Upr Aus
city: Aalst
country: Belgium
facility: Onze-Lieve-Vrouwziekenhuis Campus Aalst
state: Eflndrs
city: Gent
country: Belgium
facility: UZ Gent
state: Flemish
city: Genk
country: Belgium
facility: Ziekenhuis Oost-Limburg
state: Limburg
city: Limbourg
country: Belgium
facility: Jesse Ziekenhuis Campus Virga Jesse
city: Calgary
country: Canada
facility: Foothills Medical Centre
state: Alberta
city: Victoria
country: Canada
facility: Royal Jubilee Hospital
state: British Columbia
city: Saint John
country: Canada
facility: Saint John Regional Hospital - New Brunswick Heart Centre
state: New Brunswick
city: Montréal
country: Canada
facility: Institute de Cardiologie de Montreal (Montreal Heart Inst.)
state: Quebec
city: Montréal
country: Canada
facility: Hopital du Sacre-Coeur de
state: Quebec
city: Beijing
country: China
facility: Beijing AnZhen Hospital
state: Beijing
city: Changchun
country: China
facility: The Second Hospital of Jilin University
state: N China
city: Bad Krozingen
country: Germany
facility: Universitäts-Herzzentrum Freiburg - Bad Krozingen
state: Bad-Wur
city: Essen
country: Germany
facility: Elisabeth-Krankenhaus Essen GmbH
state: N. Rhin
city: Mainz
country: Germany
facility: UNIVERSITATSMEDIZIN der Johannes Gutenberg-Universität MainzLangenbeckstrasse
state: Rhinela
city: Leipzig
country: Germany
facility: Herzzentrum Leipzig GmbH04289
state: Saxony
city: Bad Segeberg
country: Germany
facility: Segeberger Kliniken GmbH Am Kurpark 1
state: Schlesw
city: Berlin
country: Germany
facility: Universitätsmedizin Berlin - Campus Benjamin Franklin (CBF)
city: Hamburg
country: Germany
facility: UKE Hamburg (Universitatsklinik Eppendorf)
city: Hong Kong
country: Hong Kong
facility: The University of Hong Kong (Queen Mary Hospital)
city: Hong Kong
country: Hong Kong
facility: Prince of Wales Hospital
city: Hong Kong
country: Hong Kong
facility: Queen Elizabeth Hospital
city: Napoli
country: Italy
facility: Clinica Mediterranea
state: Campani
city: Napoli
country: Italy
facility: AOU Federico II - Università degli Studi di Napoli
state: Campani
city: Cona
country: Italy
facility: Az.Osp. Universitaria di Ferrara
state: Emi-rom
city: Parma
country: Italy
facility: AOU di Parma
state: Emi-rom
city: Roma
country: Italy
facility: Policlinico Universitario A. Gemelli
state: Latium
city: Rome
country: Italy
facility: Azienda Ospedaliero Universitaria Policlinico Umberto I
state: Latium
city: Milano
country: Italy
facility: Centro Cardiologico Monzino
state: Lombard
city: Rozzano
country: Italy
facility: Istituto Clinico Humanitas
state: Lombard
city: Emmen
country: Netherlands
facility: Scheperziekenhuis Boermarkeweg
state: Drenthe
city: Leeuwarden
country: Netherlands
facility: Medisch Centrum Leeuwarden
state: Friesld
city: Dordrecht
country: Netherlands
facility: Albert Schweitzer Ziekenhuis Albert Schweitzerplaats
state: Zuid
city: Carnaxide
country: Portugal
facility: Hospital de Santa Cruz
state: Lisbon
city: Lisboa
country: Portugal
facility: Santa Maria Hospital
state: Lisbon
city: Singapore
country: Singapore
facility: National Heart Centre
state: Central Singapore
city: Singapore
country: Singapore
facility: Tan Tock Seng Hospital
state: Singapore Central
city: Málaga
country: Spain
facility: HCU Virgen de la Victoria Campus Universitario de Teatinos
state: Andalu
city: Santander
country: Spain
facility: Hospital Universitario Marqués de Valdecilla
state: Cantabr
city: Barcelona
country: Spain
facility: Hospital del Mar Passeig Maritim de la Barceloneta
state: Catalon
city: Barcelona
country: Spain
facility: Hospital Clinic I Provincial de Barcelona
state: Catalon
city: Valladolid
country: Spain
facility: Hospital Clinico Universitario de Valladolid
state: Cstleon
city: Vigo
country: Spain
facility: Hospital Alvaro Cunqueiro
state: Pontev
city: Madrid
country: Spain
facility: Hospital Universitario Doce de Octubre
city: Aarau
country: Switzerland
facility: Kantonsspital Aarau
state: Basel
city: Bern
country: Switzerland
facility: Center Inselspital Bern
city: Luzern
country: Switzerland
facility: Luzerner Kantonsspital
city: Linkou
country: Taiwan
facility: Chang Gung Memorial Hospital
state: NTaiwan
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
state: NTaiwan
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital (VGH)
state: Ntaiwan
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Chang Gung Memorial Hospital
state: STailwan
city: High Heaton
country: United Kingdom
facility: Freeman Hospital
state: Newcastle Upon Tyne
city: Portadown
country: United Kingdom
facility: Craigavon Area Hospital
state: Nirelnd
city: Southampton
country: United Kingdom
facility: Southampton University Hospital
state: Soeast
city: Bournemouth
country: United Kingdom
facility: Royal Bournemouth Hospital
state: Sowest
city: Exeter
country: United Kingdom
facility: Royal Devon & Exeter Hospital
state: Sowest
city: Cardiff
country: United Kingdom
facility: University Hospital of Wales
state: Wales
Study officials:
affiliation: Mount Sinai Medical Center,New York, NY
name: Roxana Mehran, MD
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.