XIENCE 28 Global Study

• ClinicalTrials.gov Identifier: NCT03355742
• Recruitment Status: Completed
• First Posted: November 28, 2017
• Results First Posted: February 8, 2021
• Last Update Posted: March 4, 2021
• Sponsor: Abbott Medical Devices
• Information provided by (Responsible Party): Abbott Medical Devices

Tracking Information

• First Submitted Date: November 22, 2017
• First Posted Date: November 28, 2017
• Results First Submitted Date: October 28, 2020
• Results First Posted Date: February 8, 2021
• Last Update Posted Date: March 4, 2021
• Actual Study Start Date: February 9, 2018
• Actual Primary Completion Date: October 24, 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 19, 2021)

Number of Participants With Composite of Net Adverse Clinical Endpoint (NACE), by Propensity Score Quintiles [ Time Frame: 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)

• Original Primary Outcome Measures (submitted: November 22, 2017): Net Adverse Clinical Endpoint (NACE): Composite Rate of all-cause death and all myocardial infarction (MI), stent thrombosis, stroke or major bleeding (Bleeding defined by the Bleeding Academic Research Consortium [BARC] type 2-5) [ Time Frame: From 1 to 6 months ]

Current Secondary Outcome Measures (submitted: January 19, 2021)

• Number of Participants With Composite of Net Adverse Clinical Endpoint (NACE) [ Time Frame: From 6 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 Composite of Net Adverse Clinical Endpoint (NACE) [ Time Frame: 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 Stent Thrombosis (ARC Definite/Probable, ARC Definite) [ Time Frame: From 1 to 6 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 Stent Thrombosis (ARC Definite/Probable, ARC Definite) [ Time Frame: From 6 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 Stent Thrombosis (ARC Definite/Probable, ARC Definite) [ Time Frame: 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 All Death, Cardiac Death, Vascular Death, Non-cardiovascular Death [ Time Frame: From 1 to 6 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 All Death, Cardiac Death, Vascular Death, Non-cardiovascular Death [ Time Frame: From 6 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 All Death, Cardiac Death, Vascular Death, Non-cardiovascular Death [ Time Frame: 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 All Myocardial Infarction (MI) and MI Attributed to Target Vessel (TV-MI, Modified ARC) [ Time Frame: From 1 to 6 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 Myocardial Infarction (MI) and MI Attributed to Target Vessel (TV-MI, Modified ARC) [ Time Frame: From 6 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 Myocardial Infarction (MI) and MI Attributed to Target Vessel (TV-MI, Modified ARC) [ Time Frame: 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 Composite of Cardiac Death or MI (Modified ARC) [ Time Frame: From 1 to 6 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 Cardiac Death or MI (Modified ARC) [ Time Frame: From 6 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 Cardiac Death or MI (Modified ARC) [ Time Frame: 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) [ Time Frame: From 1 to 6 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 Composite of All Death or All MI (Modified ARC) [ Time Frame: From 6 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 Composite of All Death or All MI (Modified ARC) [ Time Frame: 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 All Stroke, Ischemic Stroke and Hemorrhagic Stroke [ Time Frame: From 1 to 6 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 All Stroke, Ischemic Stroke and Hemorrhagic Stroke [ Time Frame: From 6 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 All Stroke, Ischemic Stroke and Hemorrhagic Stroke [ Time Frame: 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 Clinically-indicated Target Lesion Revascularization (CI-TLR) [ Time Frame: From 1 to 6 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 Clinically-indicated Target Lesion Revascularization (CI-TLR) [ Time Frame: From 6 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 Clinically-indicated Target Lesion Revascularization (CI-TLR) [ Time Frame: 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 Clinically-indicated Target Vessel Revascularization (CI-TVR) [ Time Frame: From 1 to 6 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 Clinically-indicated Target Vessel Revascularization (CI-TVR) [ Time Frame: From 6 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 Clinically-indicated Target Vessel Revascularization (CI-TVR) [ Time Frame: 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 Target Lesion Failure (TLF, Composite of Cardiac Death, TV-MI and CI-TLR) [ Time Frame: From 1 to 6 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 Target Lesion Failure (TLF, Composite of Cardiac Death, TV-MI and CI-TLR) [ Time Frame: From 6 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 Target Lesion Failure (TLF, Composite of Cardiac Death, TV-MI and CI-TLR) [ Time Frame: 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 Target Vessel Failure (TVF, a Composite of Cardiac Death, TV-MI and CI-TVR) [ Time Frame: From 1 to 6 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 Target Vessel Failure (TVF, a Composite of Cardiac Death, TV-MI and CI-TVR) [ Time Frame: From 6 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 Target Vessel Failure (TVF, a Composite of Cardiac Death, TV-MI and CI-TVR) [ Time Frame: 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 Bleeding Defined by the Bleeding Academic Research Consortium (BARC) Type 2-5 and Type 3-5 [ Time Frame: 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 Bleeding Defined by the BARC, Type 2-5 and Type 3-5 [ Time Frame: 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.
• Number of Participants With Bleeding Defined by BARC, Type 2-5 and Type 3-5 [ Time Frame: 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.

Original Secondary Outcome Measures (submitted: November 22, 2017)

• Net Adverse Clinical Endpoint (NACE): Composite Rate of all-cause death and all myocardial infarction (MI), stent thrombosis, stroke or major bleeding (BARC type 2-5) [ Time Frame: From 1 to 12 months ]
• Net Adverse Clinical Endpoint (NACE): Composite Rate of all-cause death and all myocardial infarction (MI), stent thrombosis, stroke or major bleeding (BARC type 2-5) [ Time Frame: From 6 to 12 months ]
• Stent thrombosis (ARC definite/probable, ARC definite) [ Time Frame: From 1 to 6 months ]
• Stent thrombosis (ARC definite/probable, ARC definite) [ Time Frame: From 6 to 12 months ]
• Stent thrombosis (ARC definite/probable, ARC definite) [ Time Frame: From 1 to 12 months ]
• All Deaths, Cardiac Death, Vascular Death, and Non-cardiovascular death [ Time Frame: From 1 to 6 months ]
• All Deaths, Cardiac Death, Vascular Death, and Non-cardiovascular death [ Time Frame: From 6 to 12 months ]
• All Deaths, Cardiac Death, Vascular Death, and Non-cardiovascular death [ Time Frame: From 1 to 12 months ]
• All MI and MI Attributed to Target Vessel (TV-MI) [ Time Frame: From 1 to 6 months ]
• All MI and MI Attributed to Target Vessel (TV-MI) [ Time Frame: From 6 to 12 months ]
• All MI and MI Attributed to Target Vessel (TV-MI) [ Time Frame: From 1 to 12 months ]
• Composite of Cardiac death or MI [ Time Frame: From 1 to 6 months ]
• Composite of Cardiac death or MI [ Time Frame: From 6 to 12 months ]
• Composite of Cardiac death or MI [ Time Frame: From 1 to 12 months ]
• Composite of all death or all MI [ Time Frame: From 1 to 6 months ]
• Composite of all death or all MI [ Time Frame: From 6 to 12 months ]
• Composite of all death or all MI [ Time Frame: From 1 to 12 months ]
• All stroke, Ischemic stroke and Hemorrhagic stroke [ Time Frame: From 1 to 6 months ]
• All stroke, Ischemic stroke and Hemorrhagic stroke [ Time Frame: From 6 to 12 months ]
• All stroke, Ischemic stroke and Hemorrhagic stroke [ Time Frame: From 1 to 12 months ]
• Clinically-indicated target lesion revascularization (CI-TLR) [ Time Frame: From 1 to 6 months ]
• Clinically-indicated target lesion revascularization (CI-TLR) [ Time Frame: From 6 to 12 months ]
• Clinically-indicated target lesion revascularization (CI-TLR) [ Time Frame: From 1 to 12 months ]
• Clinically-indicated target vessel revascularization (CI-TVR) [ Time Frame: From 1 to 6 months ]
• Clinically-indicated target vessel revascularization (CI-TVR) [ Time Frame: From 6 to 12 months ]
• Clinically-indicated target vessel revascularization (CI-TVR) [ Time Frame: From 1 to 12 months ]
• Target lesion failure (TLF, composite of Cardiac death, TV-MI and CI-TLR) [ Time Frame: From 1 to 6 months ]
• Target lesion failure (TLF, composite of Cardiac death, TV-MI and CI-TLR) [ Time Frame: From 6 to 12 months ]
• Target lesion failure (TLF, composite of Cardiac death, TV-MI and CI-TLR) [ Time Frame: From 1 to 12 months ]
• Target vessel failure (TVF, composite of Cardiac death, TV-MI and CI-TVR) [ Time Frame: From 1 to 6 months ]
• Target vessel failure (TVF, composite of Cardiac death, TV-MI and CI-TVR) [ Time Frame: From 6 to 12 months ]
• Target vessel failure (TVF, composite of Cardiac death, TV-MI and CI-TVR) [ Time Frame: From 1 to 12 months ]
• Bleeding defined by the BARC type 2-5 and type 3-5 [ Time Frame: From 1 to 6 months ]
• Bleeding defined by the BARC type 2-5 and type 3-5 [ Time Frame: From 6 to 12 months ]
• Bleeding defined by the BARC type 2-5 and type 3-5 [ Time Frame: From 1 to 12 months ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: XIENCE 28 Global Study
• Official Title: XIENCE 28 Global Study
• 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 .

• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

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

Intervention

• Device: XIENCE
  Subjects who received XIENCE family stent systems will be included.
• Drug: DAPT
  1-month clear subjects will receive 1 month of P2Y12 inhibitor and 12 months of aspirin after index procedure.
  Other Name: Dual antiplatelet therapy

Study Arms

Experimental: XIENCE

XIENCE + Short duration (1 month) of DAPT

Interventions:

• Device: XIENCE
• Drug: DAPT

Publications *

• 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.
• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: January 19, 2021): 963
• Original Estimated Enrollment (submitted: November 22, 2017): 800
• Actual Study Completion Date: April 30, 2020
• Actual Primary Completion Date: October 24, 2019 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Austria, Belgium, China, Germany, Hong Kong, Italy, Netherlands, Portugal, Singapore, Spain, Switzerland, Taiwan, United Kingdom

Administrative Information

• NCT Number: NCT03355742
• Other Study ID Numbers: ABT-CIP-10235
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Abbott Medical Devices
• Original Responsible Party: Same as current
• Current Study Sponsor: Abbott Medical Devices
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Marco Valgimigli, MD; Bern University Hospital

• PRS Account: Abbott Medical Devices
• Verification Date: February 2021