SPIRIT III Clinical Trial of the XIENCE V® Everolimus Eluting Coronary Stent System (EECSS)

Study Overview
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Brief Summary
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This study is divided into 5 arms: Randomized Clinical Trial (RCT): Prospective, randomized, active-controlled, single blind, parallel two-arm multi-center clinical trial in the United States (US) comparing XIENCE V® Everolimus Eluting Coronary Stent System (CSS) (2.5, 3.0, 3.5 mm diameter stents) to the Food and Drug Administration (FDA) approved commercially available active control TAXUS® EXPRESS2™ Paclitaxel Eluting Coronary Stent (TAXUS® EXPRESS2™ PECS) System US 2.25 mm non-randomized arm using 2.25 mm diameter XIENCE V® Everolimus Eluting CSS US 4.0 mm non-randomized arm using 4.0 mm diameter XIENCE V® Everolimus Eluting CSS US 38 mm non-randomized arm using 38 mm in length XIENCE V® Everolimus Eluting CSS Japanese non-randomized arm using XIENCE V® Everolimus Eluting CSS (2.5, 3.0, 3.5, 4.0 mm diameter stents) in Japan The TAXUS® EXPRESS2™ Paclitaxel Eluting Coronary Stent System is Manufactured by Boston Scientific.

Detailed Description
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The purpose of the SPIRIT III clinical trial is to evaluate the safety and efficacy of the XIENCE V® Everolimus Eluting Coronary Stent System (XIENCE V® EECSS). The XIENCE V® EECS (XIENCE V® arm) will be compared to an active control group represented by the FDA approved commercially available Boston Scientific TAXUS® EXPRESS2™ Paclitaxel-Eluting Coronary Stent (TAXUS® EXPRESS2™ PECS) System (TAXUS® arm). The SPIRIT III clinical trial consists of a randomized clinical trial (RCT) in the US which will enroll approximately 1,002 subjects (2:1 randomization XIENCE V® EECS : TAXUS® EXPRESS2™ PECS) with a maximum of two de novo native coronary artery lesion treatment within vessel sizes >= 2.5 mm and <= 3.75 mm. The SPIRIT III clinical trial also consists of three concurrent US non-randomized arms (2.25 mm diameter stent, 4.0 mm diameter stent and 38 mm length stent arms) and one Japanese non-randomized arm as follows: 105 subjects with a maximum of two de novo native coronary artery lesion within vessel sizes > 2.25 mm and < 2.5 mm and lesion length <= 22 mm will be enrolled concurrently in the US 2.25 mm non-randomized treatment arm 80 subjects with a maximum of two de novo native coronary artery lesion within vessel sizes > 3.75 mm and >= 4.25 mm and lesion length <= 28 mm will be enrolled concurrently in the US 4.0 mm non-randomized treatment arm 105 subjects with a maximum of two de novo native coronary artery lesion within vessel sizes > 3.0 mm and < 4.25 mm and lesion length > 24 mm and < 32 mm will be enrolled concurrently in the US 38 mm non-randomized treatment arm. 88 Japanese subjects with a maximum of two de novo native coronary artery lesions within vessel sizes >= 2.5 mm and <= 4.25 mm and lesion length <= 28 mm will be enrolled concurrently in the non-randomized Japanese arm. All subjects in the RCT and the four non-randomized arms will be screened per the protocol required inclusion/exclusion criteria. The data collected will be compared to data from the subjects enrolled into the TAXUS® arm of US RCT. Subjects enrolled in the US RCT will be sub-grouped based on whether they will have an angiographic and/or an intravascular ultrasound (IVUS) follow-up at 240 days as follows: Group A: Angiographic and IVUS follow-up at 240 days (N=240) Group B: Angiographic follow-up at 240 days (N=324) Group C: No angiographic or IVUS follow-up (N=438) All subjects will have clinical follow-up at 30, 180, 240 and 270 days (Data collected through 270 days will be submitted as the primary data set for US and Japanese market approval), and 1, 2, 3, 4, and 5 years (for annual reports). All subjects enrolled into three US non-randomized arms (N=105 for 2.25 mm arm, N=80 for 4.0 mm arm and N=105 for 38 mm stent arm) will have clinical follow-up at 30, 180, 240, and 270 days, and angiographic follow-up at 240 days. No IVUS follow-up is required for subjects enrolled in these arms. All subjects enrolled into the Japanese non-randomized arm (N=88) will have clinical follow-up at 30, 180, 240, and 270 days, and angiographic and IVUS follow-up at 240 days. All subjects who receive a bailout stent will be assigned to Group A follow-up subgroup (angiographic and IVUS follow-up at 240 days after the index procedure), regardless of their primary assignment at randomization. At sites without IVUS capability, subjects receiving bailout stent will be assigned to Group B follow-up subgroup (angiographic follow-up at 240 days after the index procedure). Angiographic follow-up is required for all bailout subjects at 240 days. Data from the US RCT will be submitted to the FDA as the primary data set for product approval for RVD >= 2.5 mm and <= 3.75 mm (2.5 mm, 3.0 mm and 3.5 mm stents). Combined data of the US trial/Japanese non-randomized arm will be submitted to the Japanese Ministry of Health, Labor and Welfare (MHLW) for Japanese approval for RVD>=2.5 mm and <= 4.25 mm (2.5 mm, 3.0 mm 3.5 mm and 4.0 mm stents). Data from the Japanese non-randomized arm will be submitted to the FDA as additional safety data. Data from the US non-randomized arms of the trial will be the primary data sets for approval for 2.25 mm diameter stent (RVD > 2.25 mm and < 2.5 mm), 4.0 mm diameter stent (RVD > 3.75 mm and <= 4.25 mm) and 38 mm length stent (RVD > 3.0 mm and <= 4.25 mm and lesion length > 24 mm and <= 32 mm), respectively in the US. A pharmacokinetic substudy will be carried out in a minimum of 5 pre-determined sites in the US and a minimum of 5 pre-determined sites in Japan. In the US, the pharmacokinetics (PK) of everolimus, as delivered by the XIENCE V® EECS will be analyzed in a subset of 15 subjects (minimum) with single vessel/lesion treatment, and up to 20 subjects with dual vessel/lesion treatment, respectively. In Japan, a minimum of 10 subjects with single vessel/lesion treatment and up to 20 subjects with dual vessel/lesion treatment will have a PK measurements performed. These subsets will include subjects receiving overlapping stents.

Official Title
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SPIRIT III: A Clinical Evaluation of the Investigational Device XIENCE V® Everolimus Eluting Coronary Stent System (EECSS) in the Treatment of Subjects With de Novo Native Coronary Artery Lesions

Conditions
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Stents, Coronary Artery Disease, Total Coronary Occlusion, Coronary Artery Restenosis, Stent Thrombosis, Vascular Disease, Myocardial Ischemia, Coronary Artery Stenosis

Intervention / Treatment
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* Device: XIENCE V® Everolimus Eluting Coronary Stent
* Device: TAXUS® EXPRESS2™ Paclitaxel Eluting Coronary Stent


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Target lesion(s) must be located in a native epicardial vessel with visually estimated diameter between >= 2.25 mm and <= 4.25 mm and a lesion length <= 32 mm The target lesion(s) must be in a major artery or branch with a visually estimated stenosis of >= 50% and < 100% with a thrombolysis in myocardial infarction (TIMI) flow of >= 1 Non-study, percutaneous intervention for lesions in a non-target vessel is allowed if done >= 90 days prior to the index procedure (subjects who received brachytherapy will be excluded from the trial) Exclusion Criteria: Located within an arterial or saphenous vein graft or distal to a diseased (vessel irregularity per angiogram and > 20% stenosed lesion by visual estimation) arterial or saphenous vein graft Lesion involving a bifurcation >= 2 mm in diameter or ostial lesion > 50% stenosed by visual estimation or side branch requiring predilatation Located in a major epicardial vessel that has been previously treated with brachytherapy Located in a major epicardial vessel that has been previously treated with percutaneous intervention < 9 months prior to index procedure Total occlusion (TIMI flow 0), prior to wire passing The target vessel contains thrombus Another significant lesion (> 40% diameter stenosis [DS]) is located in the same epicardial vessel as the target lesion

Ages Eligible for Study
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Minimum Age: 18 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>XIENCE V® Everolimus Eluting Coronary Stent System | Device: XIENCE V® Everolimus Eluting Coronary Stent<br>* Drug eluting stent implantation stent in the treatment of coronary artery disease.<br>* Other names: XIENCE V® Everolimus Eluting Coronary Stent System;|
| Active Comparator: 2<br>TAXUS® EXPRESS2™Paclitaxel Eluting Coronary Stent System | Device: TAXUS® EXPRESS2™ Paclitaxel Eluting Coronary Stent<br>* Drug eluting stent implantation stent in the treatment of coronary artery disease.<br>* Other names: TAXUS® EXPRESS2™ Paclitaxel Eluting Coronary Stent System;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary Endpoint: In-segment Late Loss (LL) | In-segment minimal lumen diameter (MLD) post-procedure minus (-) in segment MLD at 240 day follow-up and 5 mm proximal and 5mm distal to the stent equals Late Loss. MLD defined: The average of two orthogonal views (when possible) of the narrowest point within the area of assessment. | 240 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Major Secondary Endpoint: Ischemia Driven Target Vessel Failure (ID-TVF) | The composite endpoint comprised of: Cardiac death (death in which a cardiac cause cannot be excluded) Myocardial infarction (MI, classified as Q-wave and non-Q wave) Ischemia-driven target lesion revascularization (TLR) by CABG or PCI Ischemia-driven target vessel revascularization (TVR) by CABG or PCI | 270 days | 
| Target Vessel Failure (TVF) | The composite endpoint comprised of: Cardiac death (death in which a cardiac cause cannot be excluded) Myocardial infarction (MI, classified as Q-wave and non-Q wave) Ischemia-driven target lesion revascularization (TLR) by CABG or PCI Ischemia-driven target vessel revascularization (TVR) by CABG or PCI | 30 days | 
| Target Vessel Failure (TVF) | The composite endpoint comprised of: Cardiac death (death in which a cardiac cause cannot be excluded) Myocardial infarction (MI, classified as Q-wave and non-Q wave) Ischemia-driven target lesion revascularization (TLR) by CABG or PCI Ischemia-driven target vessel revascularization (TVR) by CABG or PCI | 180 days | 
| Target Vessel Failure (TVF) | The composite endpoint comprised of: Cardiac death (death in which a cardiac cause cannot be excluded) Myocardial infarction (MI, classified as Q-wave and non-Q wave) Ischemia-driven target lesion revascularization (TLR) by CABG or PCI Ischemia-driven target vessel revascularization (TVR) by CABG or PCI | 1 year | 
| Target Vessel Failure (TVF) | The composite endpoint comprised of: Cardiac death (death in which a cardiac cause cannot be excluded) Myocardial infarction (MI, classified as Q-wave and non-Q wave) Ischemia-driven target lesion revascularization (TLR) by CABG or PCI Ischemia-driven target vessel revascularization (TVR) by CABG or PCI | 2 year | 
| Target Vessel Failure (TVF) | The composite endpoint comprised of: Cardiac death (death in which a cardiac cause cannot be excluded) Myocardial infarction (MI, classified as Q-wave and non-Q wave) Ischemia-driven target lesion revascularization (TLR) by CABG or PCI Ischemia-driven target vessel revascularization (TVR) by CABG or PCI | 3 year | 
| Target Vessel Failure (TVF) | The composite endpoint comprised of: Cardiac death (death in which a cardiac cause cannot be excluded) Myocardial infarction (MI, classified as Q-wave and non-Q wave) Ischemia-driven target lesion revascularization (TLR) by CABG or PCI Ischemia-driven target vessel revascularization (TVR) by CABG or PCI | 4 year | 
| Ischemia Driven Target Lesion Revascularization (ID-TLR) | Revascularization @ target lesion associated w/ any of following: (+) functional ischemia study Ischemic symptoms & angiographic diameter stenosis ≥50% by core lab quantitative coronary angiography (QCA) Revascularization of a target lesion w/ angiographic diameter stenosis ≥70% by core laboratory QCA without angina or (+) functional study | 30 days | 
| Ischemia Driven Target Lesion Revascularization (ID-TLR) | Revascularization @ target lesion associated w/ any of following: (+) functional ischemia study Ischemic symptoms & angiographic diameter stenosis ≥50% by core lab quantitative coronary angiography (QCA) Revascularization of a target lesion w/ angiographic diameter stenosis ≥70% by core laboratory QCA without angina or (+) functional study | 180 days | 
| Ischemia Driven Target Lesion Revascularization (ID-TLR) | Revascularization @ target lesion associated w/ any of following: (+) functional ischemia study Ischemic symptoms & angiographic diameter stenosis ≥50% by core lab quantitative coronary angiography (QCA) Revascularization of a target lesion w/ angiographic diameter stenosis ≥70% by core laboratory QCA without angina or (+) functional study | 270 days | 
| Ischemia Driven Target Lesion Revascularization (ID-TLR) | Revascularization @ target lesion associated w/ any of following: (+) functional ischemia study Ischemic symptoms & angiographic diameter stenosis ≥50% by core lab quantitative coronary angiography (QCA) Revascularization of a target lesion w/ angiographic diameter stenosis ≥70% by core laboratory QCA without angina or (+) functional study | 1 years | 
| Ischemia Driven Target Lesion Revascularization (ID-TLR) | Revascularization @ target lesion associated w/ any of following: (+) functional ischemia study Ischemic symptoms & angiographic diameter stenosis ≥50% by core lab quantitative coronary angiography (QCA) Revascularization of a target lesion w/ angiographic diameter stenosis ≥70% by core laboratory QCA without angina or (+) functional study | 2 years | 
| Ischemia Driven Target Lesion Revascularization (ID-TLR) | Revascularization @ target lesion associated w/ any of following: (+) functional ischemia study Ischemic symptoms & angiographic diameter stenosis ≥50% by core lab quantitative coronary angiography (QCA) Revascularization of a target lesion w/ angiographic diameter stenosis ≥70% by core laboratory QCA without angina or (+) functional study | 3 year | 
| Ischemia Driven Target Lesion Revascularization (ID-TLR) | Revascularization @ target lesion associated w/ any of following: (+) functional ischemia study Ischemic symptoms & angiographic diameter stenosis ≥50% by core lab quantitative coronary angiography (QCA) Revascularization of a target lesion w/ angiographic diameter stenosis ≥70% by core laboratory QCA without angina or (+) functional study | 4 year | 
| Ischemia Driven Target Vessel Revascularization (ID-TVR) | Revascularization at the target vessel associated with any of the following Positive functional ischemia study Ischemic symptoms and angiographic diameter stenosis ≥ 50% by core laboratory QCA Revascularization of a target vessel with angiographic diameter stenosis ≥ 70% by core laboratory QCA without angina or positive functional study Derived from Non-Hierarchical Subject Counts of Adverse Events | 30 days | 
| Ischemia Driven Target Vessel Revascularization (ID-TVR) | Revascularization at the target vessel associated with any of the following Positive functional ischemia study Ischemic symptoms and angiographic diameter stenosis ≥ 50% by core laboratory QCA Revascularization of a target vessel with angiographic diameter stenosis ≥ 70% by core laboratory QCA without angina or positive functional study Derived from Non-Hierarchical Subject Counts of Adverse Events | 180 days | 
| Ischemia Driven Target Vessel Revascularization (ID-TVR) | Revascularization at the target vessel associated with any of the following Positive functional ischemia study Ischemic symptoms and angiographic diameter stenosis ≥ 50% by core laboratory QCA Revascularization of a target vessel with angiographic diameter stenosis ≥ 70% by core laboratory QCA without angina or positive functional study Derived from Non-Hierarchical Subject Counts of Adverse Events | 270 days | 
| Ischemia Driven Target Vessel Revascularization (ID-TVR) | Revascularization at the target vessel associated with any of the following Positive functional ischemia study Ischemic symptoms and angiographic diameter stenosis ≥ 50% by core laboratory QCA Revascularization of a target vessel with angiographic diameter stenosis ≥ 70% by core laboratory QCA without angina or positive functional study Derived from Non-Hierarchical Subject Counts of Adverse Events | 1 year | 
| Ischemia Driven Target Vessel Revascularization (ID-TVR) | Revascularization at the target vessel associated with any of the following Positive functional ischemia study Ischemic symptoms and angiographic diameter stenosis ≥ 50% by core laboratory QCA Revascularization of a target vessel with angiographic diameter stenosis ≥ 70% by core laboratory QCA without angina or positive functional study Derived from Non-Hierarchical Subject Counts of Adverse Events | 2 years | 
| Ischemia Driven Target Vessel Revascularization (ID-TVR) | Revascularization at the target vessel associated with any of the following Positive functional ischemia study Ischemic symptoms and angiographic diameter stenosis ≥ 50% by core laboratory QCA Revascularization of a target vessel with angiographic diameter stenosis ≥ 70% by core laboratory QCA without angina or positive functional study Derived from Non-Hierarchical Subject Counts of Adverse Events | 3 years | 
| Ischemia Driven Target Vessel Revascularization (ID-TVR) | Revascularization at the target vessel associated with any of the following Positive functional ischemia study Ischemic symptoms and angiographic diameter stenosis ≥ 50% by core laboratory QCA Revascularization of a target vessel with angiographic diameter stenosis ≥ 70% by core laboratory QCA without angina or positive functional study Derived from Non-Hierarchical Subject Counts of Adverse Events | 4 years | 
| Ischemia Driven Major Adverse Cardiac Event (MACE) | The composite endpoint comprised of: Cardiac death Myocardial infarction (MI, classified as Q-wave and non-Q wave) Ischemia-driven target lesion revascularization (TLR) by CABG or PCI | 30 days | 
| Ischemia Driven Major Adverse Cardiac Event (MACE) | The composite endpoint comprised of: Cardiac death Myocardial infarction (MI, classified as Q-wave and non-Q wave) Ischemia-driven target lesion revascularization (TLR) by CABG or PCI | 180 days | 
| Ischemia Driven Major Adverse Cardiac Event (MACE) | The composite endpoint comprised of: Cardiac death Myocardial infarction (MI, classified as Q-wave and non-Q wave) Ischemia-driven target lesion revascularization (TLR) by CABG or PCI | 270 days | 
| Ischemia Driven Major Adverse Cardiac Event (MACE) | The composite endpoint comprised of: Cardiac death Myocardial infarction (MI, classified as Q-wave and non-Q wave) Ischemia-driven target lesion revascularization (TLR) by CABG or PCI | 1 year | 
| Ischemia Driven Major Adverse Cardiac Event(MACE) | The composite endpoint comprised of: Cardiac death Myocardial infarction (MI, classified as Q-wave and non-Q wave) Ischemia-driven target lesion revascularization (TLR) by CABG or PCI | 2 years | 
| Ischemia Driven Major Adverse Cardiac Event (MACE) | The composite endpoint comprised of: Cardiac death Myocardial infarction (MI, classified as Q-wave and non-Q wave) Ischemia-driven target lesion revascularization (TLR) by CABG or PCI | 3 year | 
| Ischemia Driven Major Adverse Cardiac Event (MACE) | The composite endpoint comprised of: Cardiac death Myocardial infarction (MI, classified as Q-wave and non-Q wave) Ischemia-driven target lesion revascularization (TLR) by CABG or PCI | 4 year | 
| In-stent % Angiographic Binary Restenosis (% ABR) Rate | Percent of subjects with a follow-up in-stent percent diameter stenosis of ≥ 50% per quantitative coronary angiography (QCA) | at 240 days | 
| In-segment % Angiographic Binary Restenosis (% ABR) Rate | Percent of subjects with a follow-up in-segment percent diameter stenosis of ≥ 50% per QCA | 240 days | 
| Persisting Incomplete Stent Apposition, Late-acquired Incomplete Stent Apposition, Aneurysm, Thrombosis, and Persisting Dissection | Incomplete Apposition (Persisting & Late acquired): Failure to completely appose vessel wall w/ ≥1 strut separated from vessel wall w/ blood behind strut per ultrasound. Aneurysm: Abnormal vessel expansion ≥ 1.5 of reference vessel diameter. Thrombus: Protocol & ARC definition. Persisting dissection @ follow-up, present post-procedure. | at 240 days | 
| Acute Success: Clinical Device | Successful delivery and deployment of 1st implanted study stent/s @ the intended target lesion and successful withdrawal of the stent delivery system with final residual stenosis < 50%. | In-hospital | 
| Acute Success: Clinical Procedure | Successful delivery and deployment of study stent/s @ the intended target lesion and successful withdrawal of the stent delivery system with final residual stenosis < 50%. | In-hospital | 
| Proximal Late Loss | Proximal Minimum Lumen Diameter (MLD) post-procedure minus proximal MLD at follow-up (proximal defined as within 5 mm of healthy tissue proximal to stent placement) | at 240 days | 
| Distal Late Loss | Distal MLD post-procedure minus distal MLD at follow-up (distal defined as within 5 mm of healthy tissue distal to stent placement) | 240 days | 
| In-stent Late Loss | In-stent MLD post-procedure minus in-stent MLD at follow-up (in-stent defined as within the margins of the stent) | at 240 days | 
| % Volume Obstruction (% VO) | Defined as stent intimal hyperplasia and calculated as 100*(Stent Volume - Lumen Volume)/Stent Volume by IVUS. | at 240 days | 
| In-stent % Diameter Stenosis (% DS) | In-stent: Within the margins of the stent, the value calculated as 100 * (1 - in-stent MLD/RVD) using the mean values from two orthogonal views (when possible) by QCA. | at 240 days | 
| In-segment % Diameter Stenosis (% DS) | Within the margins of the stent, 5 mm proximal and 5 mm distal to the stent, the value calculated as 100 * (1 - in-segment MLD/RVD) using the mean values from two orthogonal views (when possible) by QCA. | 240 days | 
| Target Vessel Failure (TVF) | The composite endpoint comprised of: Cardiac death (death in which a cardiac cause cannot be excluded) Myocardial infarction (MI, classified as Q-wave and non-Q wave) Ischemia-driven target lesion revascularization (TLR) by CABG or PCI Ischemia-driven target vessel revascularization (TVR) by CABG or PCI | 5 years | 
| Ischemia Driven Target Lesion Revascularization (ID-TLR) | Revascularization @ target lesion associated w/ any of following: (+) functional ischemia study Ischemic symptoms & angiographic diameter stenosis ≥50% by core lab quantitative coronary angiography (QCA) Revascularization of a target lesion w/ angiographic diameter stenosis ≥70% by core laboratory QCA without angina or (+) functional study | 5 years | 
| Ischemia Driven Target Vessel Revascularization (ID-TVR) | Revascularization at the target vessel associated with any of the following Positive functional ischemia study Ischemic symptoms and angiographic diameter stenosis ≥ 50% by core laboratory QCA Revascularization of a target vessel with angiographic diameter stenosis ≥ 70% by core laboratory QCA without angina or positive functional study Derived from Non-Hierarchical Subject Counts of Adverse Events | 5 years | 
| Ischemia Driven Major Adverse Cardiac Event (MACE) | The composite endpoint comprised of: Cardiac death Myocardial infarction (MI, classified as Q-wave and non-Q wave) Ischemia-driven target lesion revascularization (TLR) by CABG or PCI | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Everolimus