Clinical trial NCT03355742: XIENCE 28 Global Study
Official title: XIENCE 28 Global Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Bleeding Disorder
Stroke, Ischemic
Stroke Hemorrhagic
Hematological Disease
Thrombocytopenia
Coagulation Disorder
Anemia
Renal Insufficiency
Coronary Artery Disease
Keywords: XIENCE
High bleeding risk (HBR)
Dual antiplatelet therapy (DAPT)
Coronary Artery Disease
Drug eluting stent (DES)
Lead sponsor: Abbott Medical Devices
Sponsor class: INDUSTRY
First posted: 2017-11-28
Enrollment: 963
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 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 .

Eligibility criteria: Inclusion Criteria:

1. 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.
2. Subject must be at least 18 years of age.
3. Subject must provide written informed consent as approved by the Ethics Committee (EC) 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.

Angiographic Inclusion Criteria

1. 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.
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 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:

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.
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 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.
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.

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: Number of Participants With Composite of Net Adverse Clinical Endpoint (NACE), by Propensity Score Quintiles
timeFrame: From 1 to 6 months
Secondary outcomes:
measure: Number of Participants With Composite of Net Adverse Clinical Endpoint (NACE)
timeFrame: From 6 to 12 months
measure: Number of Participants With Composite of Net Adverse Clinical Endpoint (NACE)
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 Participants With All Death, Cardiac Death, Vascular Death, Non-cardiovascular Death
timeFrame: From 1 to 6 months
measure: Number of Participants With All Death, Cardiac Death, Vascular Death, Non-cardiovascular Death
timeFrame: From 6 to 12 months
measure: Number of Participants With 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 Myocardial Infarction (MI) and MI Attributed to Target Vessel (TV-MI, Modified ARC)
timeFrame: From 6 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 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 Clinically-indicated Target Lesion Revascularization (CI-TLR)
timeFrame: From 6 to 12 months
measure: Number of Participants With Clinically-indicated Target Lesion Revascularization (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 Clinically-indicated Target Vessel Revascularization (CI-TVR)
timeFrame: From 6 to 12 months
measure: Number of Participants With Clinically-indicated Target Vessel Revascularization (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, a Composite of Cardiac Death, TV-MI and CI-TVR)
timeFrame: From 1 to 6 months
measure: Number of Participants With Target Vessel Failure (TVF, a Composite of Cardiac Death, TV-MI and CI-TVR)
timeFrame: From 6 to 12 months
measure: Number of Participants With Target Vessel Failure (TVF, a Composite of Cardiac Death, TV-MI and CI-TVR)
timeFrame: From 1 to 12 months
measure: Number of Participants With Bleeding Defined by the Bleeding Academic Research Consortium (BARC) Type 2-5 and Type 3-5
timeFrame: From 1 to 6 months
measure: Number of Participants With Bleeding Defined by the BARC, Type 2-5 and Type 3-5
timeFrame: From 6 to 12 months
measure: Number of Participants With Bleeding Defined by BARC, Type 2-5 and Type 3-5
timeFrame: From 1 to 12 months
Other outcomes:
Locations:
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: Hasselt
country: Belgium
facility: Jesse Ziekenhuis
state: Limburg
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 Mainz
state: Rhinela
city: Leipzig
country: Germany
facility: Herzzentrum Leipzig GmbH
state: Saxony
city: Bad Segeberg
country: Germany
facility: Segeberger Kliniken GmbH
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: Prince of Wales Hospital
state: Hong Ko
city: Hong Kong
country: Hong Kong
facility: Queen Elizabeth Hospital
state: Hong Ko
city: Hong Kong
country: Hong Kong
facility: The University of Hong Kong (Queen Mary Hospital)
state: Hong Ko
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
state: Drenthe
city: Leeuwarden
country: Netherlands
facility: Medisch Centrum Leeuwarden
state: Friesld
city: Dordrecht
country: Netherlands
facility: Albert Schweitzer Ziekenhuis
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 Singapore
state: Central
city: Singapore
country: Singapore
facility: Tan Tock Seng Hospital
state: Central
city: Malaga
country: Spain
facility: HCU Virgen de la Victoria
state: Andalu
city: Santander
country: Spain
facility: Hospital Universitario Marqués de Valdecilla
state: Cantabr
city: Barcelona
country: Spain
facility: Hospital del Mar
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 Dept of Interventional Cardiology
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 City
country: Taiwan
facility: Taipei Veterans General Hospital (VGH)
state: Ntaiwan
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
state: Ntaiwan
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Chang Gung Memorial Hospital
state: Staiwan
city: Newcastle Upon Tyne
country: United Kingdom
facility: Freeman Hospital
state: NE Engl
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 and Exeter Hospital
state: Sowest
city: Cardiff
country: United Kingdom
facility: University Hospital of Wales
state: Wales
Study officials:
affiliation: Bern University Hospital
name: Marco Valgimigli, 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.