A Clinical Evaluation of the XIENCE PRIME Small Vessel Everolimus Eluting Coronary Stent System in Japanese Population

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and effectiveness of the AVJ-09-385 Small Vessel Everolimus Eluting Coronary Stent System (EECSS) (2.25 mm diameter stent) in treatment of subjects with ischemic heart disease caused by de novo lesions.

Official Title
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SPIRIT PRIME JAPAN (SV JAPAN)

Conditions
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Vascular Disease, Myocardial Ischemia, Coronary Artery Stenosis, Coronary Disease, Coronary Artery Disease, Coronary Restenosis

Intervention / Treatment
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* Device: XIENCE PRIME SV EECSS


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject must be at least 20 years of age. Subject or a legally authorized representative must provide written informed consent prior to any study related procedure, per site requirements. Subject must have evidence of myocardial ischemia (e.g., stable or unstable angina, silent ischemia, positive functional study or a reversible change in the electrocardiogram (ECG) consistent with ischemia). Subject must be an acceptable candidate for coronary artery bypass graft (CABG) surgery. Subject must agree to undergo all protocol-required follow-up procedures. Subject must agree not to participate in any other clinical study for a period of one year following the index procedure. Angiographic Inclusion Criteria One (target) or two (one target and one non-target) de novo lesions each in a different epicardial vessel. Lesion(s) must be located in a major artery or branch with a visually estimated diameter stenosis of ≥ 50% and < 100% with a TIMI flow of ≥ 1. Lesion(s) must be located in a native coronary artery with reference vessel diameter (RVD) by visual estimation of ≥ 2.25 mm and < 2.5 mm. Lesion(s) must be located in a native coronary artery with length by visual estimation of ≤ 22 mm. Exclusion Criteria: Subject has had a known diagnosis of acute myocardial infarction (AMI) preceding the index procedure (CK-MB ≥ 2 times upper limit of normal) and CK and CK-MB have not returned to within normal limits at the time of procedure. The subject is currently experiencing clinical symptoms consistent with new onset AMI, such as nitrate-unresponsive prolonged chest pain with ischemic ECG changes. Subject has current unstable cardiac arrhythmias associated with hemodynamic instability. Subject has a known left ventricular ejection fraction (LVEF) < 40% (LVEF may be obtained at the time of the index procedure if the value is unknown and if necessary). Subject has received coronary brachytherapy in any epicardial vessel. Subject has received any organ transplant or is on a waiting list for any organ transplant. Subject is receiving or scheduled to receive chemotherapy for malignancy within 30 days prior to or within one year after the index procedure. Subject is receiving or scheduled to receive planned radiotherapy to the chest/mediastinum. Subject is receiving immunosuppressant therapy or has known immunosuppressive or autoimmune disease (e.g. human immunodeficiency virus, systemic lupus erythematosus etc.). Subject is receiving chronic anticoagulation therapy (e.g., heparin, warfarin). Subject will require Low Molecular Weight Heparin (LMWH) post-procedure. Subject has a known hypersensitivity or contraindication to aspirin, heparin, clopidogrel/ticlopidine, everolimus, cobalt, chromium, nickel, tungsten, acrylic and fluoro polymers or contrast sensitivity that cannot be adequately pre-medicated. Elective surgery is planned within 6 months after the procedure that will require discontinuing either aspirin or clopidogrel. Subject has a platelet count < 100,000 cells/mm3 or > 700,000 cells/mm3, a white blood cell (WBC) of < 3,000 cells/mm3, or documented or suspected liver disease (including laboratory evidence of hepatitis). Subject has known renal insufficiency (examples being but not limited to serum creatinine level ≥ 2.0 mg/dL, or on dialysis). Subject has a history of bleeding diathesis or coagulopathy or will refuse blood transfusions. Subject has had a cerebrovascular accident/stroke or transient ischemic neurological attack (TIA) within the past six months. Subject has had a significant gastro-intestinal or significant urinary bleed within the past six months. Subject has extensive peripheral vascular disease that precludes safe 5 French catheter insertion. Subject has other medical illness (e.g., cancer) or known history of substance abuse (alcohol, cocaine, heroin etc.) that may cause non-compliance with the protocol, confound the data interpretation or is associated with a limited life expectancy (i.e., less than one year). Subject is currently participating in another clinical study that has not yet completed its primary endpoint. 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*. Whether a subject who met this criterion will be asked for pregnancy test will be decided per site standard. However, subject enrollment in the study is not allowed without pregnancy test result. Angiographic Exclusion Criteria All angiographic exclusion criteria are based on visual estimation. Target lesion located within an arterial or saphenous vein graft or distal to a diseased (vessel irregularity per angiogram and > 20% stenosed lesion) arterial or saphenous vein graft. Target lesion involving a bifurcation with a side branch ≥ 2 mm in diameter and/or ostial lesion > 40% stenosed or side branch requiring protection guidewire, or side branch requiring dilatation. Target lesion with total occlusion (TIMI flow 0), prior to crossing with the wire. Another lesion requiring revascularization is located in the same epicardial vessel of the target lesion. Restenotic lesion. Aorto-ostial target lesion (within 3 mm of the aorta junction). Lesion in the left main trunk (both target and non-target). Lesion located within 2 mm of the origin of the LAD or LCX. Extreme angulation (≥ 90 °) or excessive tortuosity (≥ two 45° angles) proximal to or within the target lesion. Heavy calcification proximal to or within the target lesion. Target vessel contains thrombus as indicated in the angiographic images. Target lesion has a high probability that a procedure other than pre-dilatation and stenting will be required at the time of index procedure for treatment of the target vessel (e.g. rotablator, DCA, cutting balloon). Target vessel is previously treated* with any type of PCI (e.g. balloon angioplasty, stent, rotablator, DCA, cutting balloon) within 9 months of index procedure. Non-target vessel was previously treated with any type of PCI within 90 days of index procedure. Additional clinically significant lesion(s) in the target vessel or side branch for which PCI may be required within 90 days after the index procedure. Target lesion must be separated ≥ 5 mm from a previously treated lesion (stenosis within 5 mm of previously treated lesion is regarded as restenosis).

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: XIENCE PRIME SV EECSS<br>XIENCE PRIME SV EECSS: Small Vessel Everolimus Eluting Coronary Stent System | Device: XIENCE PRIME SV EECSS<br>* Patients receiving XIENCE PRIME SV EECSS<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite Endpoint of Cardiac Death/TV-MI/CI-TLR (TLF) | Target lesion failure (TLF) is the composite of any of the following adverse events: Cardiac death, target vessel myocardial infarction (TV-MI) (per Protocol definition), Clinically indicated target lesion revascularization (CI-TLR) | 9 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Device Success (Lesion Based Analysis, Only for XIENCE PRIME SV) | Device success is achievement final in-stent residual diameter stenosis of < 50% (by QCA). If adjunct treatment devices other than protocol defined device is used for target lesion treatment, malfunction of the investigational device occurring during the index procedure, are not regarded as device success. Use of a bail-out stent is still regarded as device success unless a device malfunction has occured. If QCA %DS is not available, the data is not included in analyses. | The period during an in-hospital stay of less than or equal to 7 days post index procedure. | 
| Procedural Success(Subject Base Analysis) | Procedure success is defined as achievement of a final in-stent diameter stenosis of < 50% (by QCA) using the investigational device (AVJ-09-385), without the occurrence MACE during the hospital stay (up to 7 days if a subject still in the hospital). If QCA %DS is not available, the data is not included in analyses. | The period during an in-hospital stay of less than or equal to 7 days post index procedure. | 
| Percent Diameter Stenosis (%DS), In-segment, In-stent, Proximal and Distal | IN-STENT is defined as within the margins of the stent. IN-SEGMENT is defined as within the margins of the stent and 5 mm proximal and 5 mm distal to the stent. PROXIMAL is defined as within 5 mm of healthy tissue proximal to stent placement DISTAL is defined as within 5 mm of healthy tissue distal to stent placement | 8 months | 
| Late Loss (LL), In-segment, In-stent, Proximal and Distal | LATE LOSS (LL) calculated as MINIMUM LUMEN DIAMETER [MLD] post-procedure MINUS MLD at follow-up: In-segment Late Loss: in-segment MLD post-procedure - in segment MLD at follow-up In-stent Late Loss: in-stent MLD post-procedure - in-stent MLD at follow-up Proximal Late Loss: proximal MLD post-procedure - proximal MLD at follow-up (proximal defined as within 5 mm of healthy tissue proximal to stent placement) Distal Late Loss: distal MLD post-procedure - distal MLD at follow-up (distal defined as within 5 mm of healthy tissue distal to stent placement) | 8 months | 
| Angiographic Binary Restenosis (ABR), In-segment, In-stent, Proximal and Distal | IN-STENT is defined as within the margins of the stent. IN-SEGMENT is defined as within the margins of the stent and 5 mm proximal and 5 mm distal to the stent. PROXIMAL is defined as within 5 mm of healthy tissue proximal to stent placement DISTAL is defined as within 5 mm of healthy tissue distal to stent placement | 8 months | 
| Death (Cardiac, Vascular, Non-Cardiovascular, Per ARC Definition) | DEATH (Per ARC Circulation 2007; 115: 2344-2351) 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. | 1 month | 
| Death (Cardiac, Vascular, Non-Cardiovascular, Per ARC Definition) | DEATH (Per ARC Circulation 2007; 115: 2344-2351) 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. | 9 months | 
| Myocardial Infarction (MI: QMI and NQMI, Both Per SPIRIT III Protocol and Per ARC Definitions) | Definitions in SPIRIT III Study: Q wave MI: Development of new, pathological Q wave on the ECG Non-Q wave MI: Elevation of CK levels to >=two times the upper limit of normal (ULN) with elevated CK-MB in the absence of new pathological Q waves Per ARC definition as published in 'Academic Research Consortium., Clinical end points in coronary stent trials: a case for standardized definitions.' Circulation 2007; 115: 2344-2351 | 1 month | 
| Myocardial Infarction (MI: QMI and NQMI, Both Per SPIRIT III Protocol and Per ARC Definitions) | Definitions in SPIRIT III Study: Q wave MI: Development of new, pathological Q wave on the ECG Non-Q wave MI: Elevation of CK levels to >=two times the upper limit of normal (ULN) with elevated CK-MB in the absence of new pathological Q waves Per ARC definition as published in 'Academic Research Consortium., Clinical end points in coronary stent trials: a case for standardized definitions.' Circulation 2007; 115: 2344-2351 | 9 months | 
| Myocardial Infarction (MI: QMI and NQMI, Both Per SPIRIT III Protocol and Per ARC Definitions) Attributable to Target Vessel (TV-MI) | Definitions in SPIRIT III Study: Q wave MI: Development of new, pathological Q wave on the ECG Non-Q wave MI: Elevation of CK levels to >=two times the upper limit of normal (ULN) with elevated CK-MB in the absence of new pathological Q waves Per ARC definition as published in 'Academic Research Consortium., Clinical end points in coronary stent trials: a case for standardized definitions.' Circulation 2007; 115: 2344-2351 | 1 month | 
| Myocardial Infarction (MI: QMI and NQMI, Both Per SPIRIT III Protocol and Per ARC Definitions) Attributable to Target Vessel (TV-MI) | Definitions in SPIRIT III Study: Q wave MI: Development of new, pathological Q wave on the ECG Non-Q wave MI: Elevation of CK levels to >=two times the upper limit of normal (ULN) with elevated CK-MB in the absence of new pathological Q waves Per ARC definition as published in 'Academic Research Consortium., Clinical end points in coronary stent trials: a case for standardized definitions.' Circulation 2007; 115: 2344-2351 | 9 months | 
| Myocardial Infarction (MI: QMI and NQMI, Both Per SPIRIT III Protocol and Per ARC Definitions) Not Attributable to Target Vessel (NTV-MI) | Definitions in SPIRIT III Study: Q wave MI: Development of new, pathological Q wave on the ECG Non-Q wave MI: Elevation of CK levels to >=two times the upper limit of normal (ULN) with elevated CK-MB in the absence of new pathological Q waves Per ARC definition as published in 'Academic Research Consortium., Clinical end points in coronary stent trials: a case for standardized definitions.' Circulation 2007; 115: 2344-2351 | 1 month | 
| Myocardial Infarction (MI: QMI and NQMI, Both Per SPIRIT III Protocol and Per ARC Definitions) Not Attributable to Target Vessel (NTV-MI) | Definitions in SPIRIT III Study: Q wave MI: Development of new, pathological Q wave on the ECG Non-Q wave MI: Elevation of CK levels to >=two times the upper limit of normal (ULN) with elevated CK-MB in the absence of new pathological Q waves Per ARC definition as published in 'Academic Research Consortium., Clinical end points in coronary stent trials: a case for standardized definitions.' Circulation 2007; 115: 2344-2351 | 9 months | 
| Target Lesion Revascularization (TLR, Per ARC Definition) | Any revascularization for in-segment restenosis will be considered TLR.Segment is defined as the area within the margins of the stent and 5 mm proximal and 5 mm distal to the stent. Revascularization was considered clinically indicated if there was >70% diameter stenosis on angiography or >50% stenosis together with a positive stress test or ischaemic symptoms. | 1 month | 
| Target Lesion Revascularization (TLR, Per ARC Definition) | Any revascularization for in-segment restenosis will be considered TLR. Segment is defined as the area within the margins of the stent and 5 mm proximal and 5 mm distal to the stent. Revascularization was considered clinically indicated if there was >70% diameter stenosis on angiography or >50% stenosis together with a positive stress test or ischaemic symptoms. | 9 months | 
| Target Lesion Revascularization (TLR, Per ARC Definition) Clinically-indicated TLR (CI-TLR) | Any revascularization for in-segment restenosis will be considered TLR. Segment is defined as the area within the margins of the stent and 5 mm proximal and 5 mm distal to the stent. Revascularization was considered clinically indicated if there was >70% diameter stenosis on angiography or >50% stenosis together with a positive stress test or ischaemic symptoms. | 1 month | 
| Target Lesion Revascularization (TLR, Per ARC Definition) Clinically-indicated TLR (CI-TLR) | Any revascularization for in-segment restenosis will be considered TLR. Segment is defined as the area within the margins of the stent and 5 mm proximal and 5 mm distal to the stent. Revascularization was considered clinically indicated if there was >70% diameter stenosis on angiography or >50% stenosis together with a positive stress test or ischaemic symptoms. | 9 months | 
| Target Lesion Revascularization (TLR, Per ARC Definition) Not Clinically-indicated TLR (NCI-TLR) | Any revascularization for in-segment restenosis will be considered TLR. Segment is defined as the area within the margins of the stent and 5 mm proximal and 5 mm distal to the stent. Revascularization was considered clinically indicated if there was >70% diameter stenosis on angiography or >50% stenosis together with a positive stress test or ischaemic symptoms. | 1 month | 
| Target Lesion Revascularization (TLR, Per ARC Definition) Not Clinically-indicated TLR (NCI-TLR) | Any revascularization for in-segment restenosis will be considered TLR. Segment is defined as the area within the margins of the stent and 5 mm proximal and 5 mm distal to the stent. Revascularization was considered clinically indicated if there was >70% diameter stenosis on angiography or >50% stenosis together with a positive stress test or ischaemic symptoms. | 9 months | 
| Target Vessel Revascularization (TVR, Per ARC Definition) | 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. Revascularization was considered clinically indicated if there was >70% diameter stenosis on angiography or >50% stenosis together with a positive stress test or ischaemic symptoms. | 1 month | 
| Target Vessel Revascularization (TVR, Per ARC Definition) | 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. Revascularization was considered clinically indicated if there was >70% diameter stenosis on angiography or >50% stenosis together with a positive stress test or ischaemic symptoms. | 9 months | 
| Target Vessel Revascularization (TVR, Per ARC Definition) Clinically-indicated TVR (CI-TVR) | 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. Revascularization was considered clinically indicated if there was >70% diameter stenosis on angiography or >50% stenosis together with a positive stress test or ischaemic symptoms. | 1 month | 
| Target Vessel Revascularization (TVR, Per ARC Definition) Clinically-indicated TVR (CI-TVR) | 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. Revascularization was considered clinically indicated if there was >70% diameter stenosis on angiography or >50% stenosis together with a positive stress test or ischaemic symptoms. | 9 months | 
| Target Vessel Revascularization (TVR, Per ARC Definition) Not Clinically-indicated TVR (NCI-TVR) | 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. Revascularization was considered clinically indicated if there was >70% diameter stenosis on angiography or >50% stenosis together with a positive stress test or ischaemic symptoms. | 1 month | 
| Target Vessel Revascularization (TVR, Per ARC Definition) Not Clinically-indicated TVR (NCI-TVR) | 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. Revascularization was considered clinically indicated if there was >70% diameter stenosis on angiography or >50% stenosis together with a positive stress test or ischaemic symptoms. | 9 months | 
| Composite Endpoint of Cardiac Death/All MI |  | 1 month | 
| Composite Endpoint of Cardiac Death/All MI |  | 9 months | 
| Composite Endpoint of All Death/All MI/All Revascularization (DMR) | DMR event (all death, all MI (per protocol or per ARC), all revascularization, respectively). | 1 month | 
| Composite Endpoint of All Death/All MI/All Revascularization (DMR) | DMR event (all death, all MI (per protocol or per ARC), all revascularization, respectively). | 9 months | 
| Composite Endpoint of Cardiac Death/TV-MI/CI-TLR (TLF) | Target lesion failure (TLF) is defined as a composite of cardiac death, target-vessel related myocardial infarction (TV-MI) and clinically-indicated target lesion revascularization (CI-TLR). | 1 month | 
| Composite Endpoint of Cardiac Death/All MI/CI-TLR (MACE) | Major adverse cardiac events (MACE) is defined as the composite of cardiac death, all myocardial-infarction, and clinically-indicated target lesion revascularization (CI-TLR). | 1 month | 
| Composite Endpoint of Cardiac Death, All MI and CI-TLR (MACE) | Major adverse cardiac events (MACE) is defined as the composite of cardiac death, all myocardial-infarction, and clinically-indicated target lesion revascularization (CI-TLR). | 9 months | 
| All Coronary Revascularization |  | 1 months | 
| All Coronary Revascularization |  | 9 months | 
| Acute Stent Thrombosis | Stent thrombosis (ST) was defined according to the ARC guidelines as follows: definite: acute coronary syndrome and angiographic or pathological confirmation of ST; probable: unexplained death ≤30 days or target vessel MI without angiographic information; and possible: unexplained death >30 days after stent placement. | <24 hours | 
| Subacute Stent Thrombosis | Stent thrombosis was defined according to the ARC guidelines as follows: definite: acute coronary syndrome and angiographic or pathological confirmation of ST; probable: unexplained death ≤30 days or target vessel MI without angiographic information; and possible: unexplained death >30 days after stent placement. | 1-30 days | 
| Acute/Subacute Stent Thrombosis | Stent thrombosis was defined according to the ARC guidelines as follows: definite: acute coronary syndrome and angiographic or pathological confirmation of ST; probable: unexplained death ≤30 days or target vessel MI without angiographic information; and possible: unexplained death >30 days after stent placement. | 0-30 days | 
| Late Stent Thrombosis | Stent thrombosis was defined according to the ARC guidelines as follows: definite: acute coronary syndrome and angiographic or pathological confirmation of ST; probable: unexplained death ≤30 days or target vessel MI without angiographic information; and possible: unexplained death >30 days after stent placement. | 31 - 298 days | 
| Overall Stent Thrombosis | Stent thrombosis was defined according to the ARC guidelines as follows: definite: acute coronary syndrome and angiographic or pathological confirmation of ST; probable: unexplained death ≤30 days or target vessel MI without angiographic information; and possible: unexplained death >30 days after stent placement. | 0 - 298 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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drug eluting stents, small vessel, Stents, Everolimus, Angioplasty