XIENCE 28 Global Study

Not Applicable

Completed

Conditions: Hematological Disease
Renal Insufficiency
Stroke Hemorrhagic
Thrombocytopenia
Anemia
Bleeding Disorder
Stroke, Ischemic
Coagulation Disorder
Coronary Artery Disease

Interventions: Device: XIENCE
Drug: DAPT

Registration Number: NCT03355742

Lead Sponsor: Abbott Medical Devices

Brief Summary: XIENCE 28 Global Study is a prospective, single arm, multi-center, open label, non-randomized trial to further evaluate the 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, XIENCE PROX EECSS, XIENCE ProA EECSS or XIENCE Sierra EECSS of coronary drug-eluting stents

Detailed Description: The XIENCE 28 Global Study will evaluate the safety of 1-month DAPT following XIENCE implantation in HBR patients. A minimum of 800 to a maximum of 960 subjects will be registered from approximately 50 sites globally and subject registration is capped at 120 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 continue 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 Global Study will be compared with the historical control of non-complex HBR subjects treated with standard DAPT up to 12 months from the XIENCE V USA Study .

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 963

Inclusion Criteria

Subject is considered at 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. Subjects ≥ 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.
Subject must be at least 18 years of age.
Subject must provide written informed consent as approved by the Ethics Committee (EC) of the respective clinical site prior to any trial related procedure.
Subject is willing to comply with all protocol requirements, including agreement to stop taking P2Y12 inhibitor at 1 month, if eligible per protocol.
Subject must agree not to participate in any other clinical trial for a period of one year following the index procedure.

Angiographic Inclusion Criteria

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

Note:
1. 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.
2. 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.
Target lesion must be located in a native coronary artery with visually estimated reference vessel diameter between 2.25 mm and 4.25 mm.
Exclusive use of XIENCE family of stent systems during the index procedure.
Target lesion has been treated successfully, which is defined as achievement of a final in-stent residual diameter stenosis of <20% with final thrombolysis in myocardial infarction (TIMI-3) flow assessed by online quantitative angiography or visual estimation, with no residual dissection National Heart, Lung, and Blood Institute (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

Subject with an indication for the index procedure of acute ST-segment elevation MI (STEMI).
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.
Subject with implantation of another drug-eluting stent (other than XIENCE) within 12 months prior to index procedure.
Subject has a known left ventricular ejection fraction (LVEF) <30%.
Subject judged by physician as inappropriate for discontinuation from P2Y12 inhibitor use at 1 month, due to another condition requiring chronic P2Y12 inhibitor use.
Subject with planned surgery or procedure necessitating discontinuation of P2Y12 inhibitor within 1 month following index procedure.
Subject with a current medical condition with a life expectancy of less than 12 months.
Subject intends to participate in an investigational drug or device trial within 12 months following the index procedure.
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 subjects 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 trial design, product characteristics and/or trial population.
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.
Subject is currently participating in another clinical trial that has not yet completed its primary endpoint.

Angiographic Exclusion Criteria

Target lesion is in a left main location.
Target lesion is located within an arterial or saphenous vein graft.
Target lesion is restenotic from a previous stent implantation.
Target lesion is a chronic total occlusion (CTO, defined as lesion with TIMI flow 0 for at least 3 months).
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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
XIENCE	XIENCE	XIENCE + Short duration (1 month) of DAPT
XIENCE	DAPT	XIENCE + Short duration (1 month) of DAPT

Primary Outcome Measures

Name	Time	Method
Number of Participants With Composite of Net Adverse Clinical Endpoint (NACE), by Propensity Score Quintiles	From 1 to 6 months	Net Adverse Clinical Endpoint (NACE): A composite rate of all-cause death, all myocardial infarction (modified Academic Research Consortium \[ARC\]), stent thrombosis (ARC definite or probable), stroke or major bleeding (Bleeding defined by the Bleeding Academic Research Consortium \[BARC\] type 2-5)

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Stent Thrombosis (ARC Definite/Probable, ARC Definite)	From 1 to 12 months	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
Number of Participants With Composite of Cardiac Death or MI (Modified ARC)	From 1 to 12 months	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
Number of Participants With Composite of All Death or All MI (Modified ARC)	From 1 to 12 months	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. 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 * Spontaneous MI (\> 48h following PCI, \> 72h following CABG): CK-MB \> URL or Troponin \> URL with baseline value \< URL
Number of Participants With Clinically-indicated Target Lesion Revascularization (CI-TLR)	From 1 to 12 months	TLR is defined as any repeat percutaneous intervention of the target lesion (the treated segment from 5 mm proximal to the stent and to 5 mm distal to the stent) 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 CI by the investigator prior to repeat angiography. A revascularization is considered CI if angiography at follow-up shows a percent diameter stenosis ≥ 50% and if any one below 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 TLR with a diameter stenosis ≥70% in the absence of the above mentioned ischemic signs or symptoms.
Number of Participants With Composite of Net Adverse Clinical Endpoint (NACE)	From 1 to 12 months	Net Adverse Clinical Endpoint (NACE): A composite rate of all-cause death, all myocardial infarction (modified Academic Research Consortium \[ARC\]), stent thrombosis (ARC definite or probable), stroke or major bleeding (Bleeding defined by the Bleeding Academic Research Consortium \[BARC\] type 2-5)
Number of Participants With Target Lesion Failure (TLF, Composite of Cardiac Death, TV-MI and CI-TLR)	From 1 to 12 months	TLF is defined as a composite of all cardiac death, myocardial infarction attributed to target vessel or clinically-indicated TLR.
Number of Participants With Bleeding Defined by the Bleeding Academic Research Consortium (BARC) Type 2-5 and Type 3-5	From 1 to 6 months	Bleeding per Bleeding Academic Research Consortium (BARC)definitions are as follows: Type 0 Type 1 Type 2 Type 3 Type 4 Type 5 Where, Type 0 indicates no bleeding and type 5 indicates fatal bleeding.
Number of Participants With All Death, Cardiac Death, Vascular Death, Non-cardiovascular Death	From 1 to 12 months	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.
Number of Participants With Target Vessel Failure (TVF, a Composite of Cardiac Death, TV-MI and CI-TVR)	From 1 to 12 months	TVF is defined as a composite of cardiac death, MI attributed to target vessel, clinically-indicated TLR, or clinically-indicated TVR, non-TLR.
Number of Participants With All Myocardial Infarction (MI) and MI Attributed to Target Vessel (TV-MI, Modified ARC)	From 1 to 12 months	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
Number of Participants With All Stroke, Ischemic Stroke and Hemorrhagic Stroke	From 1 to 12 months	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)
Number of Participants With Bleeding Defined by BARC, Type 2-5 and Type 3-5	From 1 to 12 months	Bleeding per Bleeding Academic Research Consortium (BARC)definitions are as follows: Type 0 Type 1 Type 2 Type 3 Type 4 Type 5 Where, Type 0 indicates no bleeding and type 5 indicates fatal bleeding.
Number of Participants With Clinically-indicated Target Vessel Revascularization (CI-TVR)	From 1 to 12 months	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.
Number of Participants With Bleeding Defined by the BARC, Type 2-5 and Type 3-5	From 6 to 12 months	Bleeding per Bleeding Academic Research Consortium (BARC)definitions are as follows: Type 0 Type 1 Type 2 Type 3 Type 4 Type 5 Where, Type 0 indicates no bleeding and type 5 indicates fatal bleeding.

Trial Locations

Locations (52): National Heart Centre Singapore
🇸🇬
Singapore, Central, Singapore
Tan Tock Seng Hospital
🇸🇬
Singapore, Central, Singapore
Luzerner Kantonsspital
🇨🇭
Luzern, Switzerland
National Taiwan University Hospital
🇨🇳
Taipei, Ntaiwan, Taiwan
University Hospital of Wales
🇬🇧
Cardiff, Wales, United Kingdom
Chang Gung Memorial Hospital
🇨🇳
LinKou, Ntaiwan, Taiwan
Taipei Veterans General Hospital (VGH)
🇨🇳
Taipei City, Ntaiwan, Taiwan
Hospital Clinic I Provincial de Barcelona
🇪🇸
Barcelona, Catalon, Spain
Southampton University Hospital
🇬🇧
Southampton, Soeast, United Kingdom
Hospital de Santa Cruz
🇵🇹
Carnaxide, Lisbon, Portugal
Hospital Universitario Doce de Octubre
🇪🇸
Madrid, Spain
Center Inselspital Bern
🇨🇭
Bern, Switzerland
HCU Virgen de la Victoria
🇪🇸
Malaga, Andalu, Spain
Hospital Clinico Universitario de Valladolid
🇪🇸
Valladolid, Cstleon, Spain
Albert Schweitzer Ziekenhuis
🇳🇱
Dordrecht, Zuid, Netherlands
Kantonsspital Aarau
🇨🇭
Aarau, Basel, Switzerland
Kaohsiung Chang Gung Memorial Hospital
🇨🇳
Kaohsiung, Staiwan, Taiwan
Hospital Universitario Marqués de Valdecilla
🇪🇸
Santander, Cantabr, Spain
Hospital Alvaro Cunqueiro Dept of Interventional Cardiology
🇪🇸
Vigo, Pontev, Spain
Craigavon Area Hospital
🇬🇧
Portadown, Nirelnd, United Kingdom
Hospital del Mar
🇪🇸
Barcelona, Catalon, Spain
Santa Maria Hospital
🇵🇹
Lisboa, Lisbon, Portugal
Policlinico Universitario A. Gemelli
🇮🇹
Roma, Latium, Italy
Azienda Ospedaliero Universitaria Policlinico Umberto I
🇮🇹
Rome, Latium, Italy
Freeman Hospital
🇬🇧
Newcastle Upon Tyne, NE Engl, United Kingdom
Royal Bournemouth Hospital
🇬🇧
Bournemouth, Sowest, United Kingdom
Royal Devon and Exeter Hospital
🇬🇧
Exeter, Sowest, United Kingdom
Kepler Universitätsklinikum GmbH
🇦🇹
Linz, Upr Aus, Austria
UZ Gent
🇧🇪
Gent, Flemish, Belgium
Onze-Lieve-Vrouwziekenhuis Campus Aalst
🇧🇪
Aalst, Eflndrs, Belgium
Ziekenhuis Oost-Limburg
🇧🇪
Genk, Limburg, Belgium
Jesse Ziekenhuis
🇧🇪
Hasselt, Limburg, Belgium
Beijing AnZhen Hospital
🇨🇳
Beijing, Beijing, China
The Second Hospital of Jilin University
🇨🇳
Changchun, N China, China
Universitäts-Herzzentrum Freiburg - Bad Krozingen
🇩🇪
Bad Krozingen, Bad-wur, Germany
UNIVERSITATSMEDIZIN der Johannes Gutenberg-Universität Mainz
🇩🇪
Mainz, Rhinela, Germany
Herzzentrum Leipzig GmbH
🇩🇪
Leipzig, Saxony, Germany
Segeberger Kliniken GmbH
🇩🇪
Bad Segeberg, Schlesw, Germany
Universitätsmedizin Berlin - Campus Benjamin Franklin (CBF)
🇩🇪
Berlin, Germany
Prince of Wales Hospital
🇭🇰
Hong Kong, Hong Ko, Hong Kong
The University of Hong Kong (Queen Mary Hospital)
🇭🇰
Hong Kong, Hong Ko, Hong Kong
AOU Federico II - Università degli Studi di Napoli
🇮🇹
Napoli, Campani, Italy
Clinica Mediterranea
🇮🇹
Napoli, Campani, Italy
Az.Osp. Universitaria di Ferrara
🇮🇹
Cona, Emi-rom, Italy
AOU di Parma
🇮🇹
Parma, Emi-rom, Italy
Centro Cardiologico Monzino
🇮🇹
Milano, Lombard, Italy
Istituto Clinico Humanitas
🇮🇹
Rozzano, Lombard, Italy
Scheperziekenhuis
🇳🇱
Emmen, Drenthe, Netherlands
Medisch Centrum Leeuwarden
🇳🇱
Leeuwarden, Friesld, Netherlands
Elisabeth-Krankenhaus Essen GmbH
🇩🇪
Essen, N. Rhin, Germany
UKE Hamburg (Universitatsklinik Eppendorf)
🇩🇪
Hamburg, Germany
Queen Elizabeth Hospital
🇭🇰
Hong Kong, Hong Ko, Hong Kong