SPIRIT V: A Clinical Evaluation of the XIENCE V® Everolimus Eluting Coronary Stent System in the Treatment of Patients With de Novo Coronary Artery Lesions (Diabetic Sub-Study)

Study Overview
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Brief Summary
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The purpose of this Clinical Evaluation is a continuation in the assessment of the performance of the XIENCE V® Everolimus Eluting Coronary Stent System (XIENCE V® EECSS) in the treatment of patients with de novo coronary artery lesions in patients (Diabetic sub-study).

Detailed Description
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The SPIRIT V Clinical Evaluation consists of two concurrent studies,the Diabetic sub-study and the Registry. The SPIRIT V Diabetic sub-study is a prospective, randomized, active-controlled, single blind, parallel two-arm multi-center study comparing the XIENCE V® EECSS to the TAXUS® Liberté™ in the treatment of diabetic patients with coronary artery lesions who will fulfill the eligibility criteria. Approximately 300 patients will be randomized (2:1) against the TAXUS® Liberté™ coronary stent system. These patients will be recruited in up to 40 selected sites. The long term safety and efficacy of the XIENCE V EECSS have been demonstrated in the SPIRIT FIRST trial up to 5 years, the SPIRIT II trial up to 4 years, and in the SPIRIT III Randomized Control Trial (RCT) up to 3 years. In addition, these pre-approval studies have shown low rates of Target Vessel Failure and Major Adverse Cardiac Events (MACE) that were observed to plateau or gradually decline after about 1 year and were consistently lower than the comparator arm of each study. This benefit in MACE is sustained for up to 5 years and is also independent of the first year results. The post approval SPIRIT V study demonstrated that the use of the XIENCE EECSS in complex lesions in a real-world population resulted in 1 year MACE, Stent Thrombosis and Target Lesion Revascularization rates that are comparable to those of the previously mentioned pre-approval studies which included patients with more restricted inclusion / exclusion criteria. Therefore, based on existing data from these trials, Abbott Vascular has decided to discontinue further follow up in the SPIRIT V Diabetic study after 1 year.

Official Title
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SPIRIT V: A Clinical Evaluation of the XIENCE V® Everolimus Eluting Coronary Stent System in the Treatment of Patients With de Novo Coronary Artery Lesions

Conditions
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Coronary Disease, Coronary Artery Disease, Coronary Restenosis

Intervention / Treatment
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* Device: TAXUS® Liberté™
* Device: XIENCE V® EECSS


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: at least 18 years able to verbally confirm understanding of risks, benefits and treatment alternatives of receiving the XIENCE V® EECSS and he/she or his/her legally authorized representative provides written informed consent prior to any study related procedure, as approved by the appropriate Medical Ethics Committee of the respective clinical site diagnosed with diabetes, as documented by medical history. evidence of myocardial ischemia acceptable candidate for coronary artery bypass grafting (CABG) surgery agree to undergo all clinical investigation plan (CIP)-required follow-up examinations artery morphology and disease is suitable to be optimally treated with a maximum of 4 planned stents maximum of one, de novo, target lesion per native major epicardial vessel or side branch target vessel reference diameter must be between 2.25 mm and 4.0 mm by visual estimate target lesion ≤ 28 mm in length by visual estimate target lesion must be in a major artery or branch with a visually estimated stenosis of > 50% and < 100% and a TIMI flow > 1 Exclusion Criteria: known diagnosis of acute myocardial infarction within 72 hours preceding the index procedure current unstable arrhythmias Left ventricular ejection fraction < 30% received a heart or any other organ transplant or is on a waiting list for any organ transplant receiving or scheduled to receive chemotherapy or radiation therapy within 30 days prior to or after the procedure. receiving immunosuppression therapy or has known immunosuppressive or autoimmune disease known hypersensitivity or contraindication to specific agents elective surgery is planned within the first 9 months after the procedure that will require discontinuing either aspirin or clopidogrel platelet count limits, white blood cell limits or documented or suspected liver disease renal insufficiency history of bleeding diathesis or coagulopathy or will refuse blood transfusions Cerebrovascular accident or transient ischemic attack within the past 6 months significant GI or urinary bleed within the past 6 months history of other medical illness (e.g., cancer or congestive heart failure) or known history of substance abuse that may cause non-compliance with the CIP, confound the data interpretation or is associated with a limited life expectancy (i.e. less than one year) Target lesion meets any of the following criteria: In-stent restenotic aorto-ostial location (within 3 mm) left main location located within 2 mm of the origin of the left anterior descending artery (LAD) or left circumflex artery (LCX) located within an arterial or saphenous vein graft or distal to a diseased arterial or saphenous vein graft (defined as vessel irregularity per angiogram and > 20% stenosed lesion by visual estimation) lesion involving a side branch ≥ 2.5 mm in diameter lesion involving a side branch with > 50% stenosis by visual estimation Lesion involving a side branch requiring predilatation located in a major epicardial vessel that has been previously treated with brachytherapy located in a major epicardial vessel or a side branch that has been previously treated with any type of percutaneous intervention (e.g., balloon angioplasty, cutting balloon, atherectomy), < 9 months prior to the index procedure total occlusion (TIMI flow 0), prior to wire crossing excessive tortuosity proximal to or within the lesion extreme angulation (≥ 90%) proximal to or within the lesion heavy calcification The target vessel contains visible thrombus Patient has a high probability that a procedure other than pre-dilatation, stenting and post-dilatation will be required at the time of index procedure for treatment of the target vessel (e.g. brachytherapy) Patient has additional clinically significant lesion(s) (> 50% diameter stenosis) in a target vessel or side branch for which an intervention within 9 months after the index procedure may be required

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 |
| --- | --- |
| Active Comparator: TAXUS® Liberté™<br> | Device: TAXUS® Liberté™<br>* Drug eluting stent implantation stent in the treatment of coronary artery disease in participants with Diabetes<br>|
| Active Comparator: XIENCE V® EECSS<br> | Device: XIENCE V® EECSS<br>* Drug eluting stent implantation stent in the treatment of coronary artery disease in participants with Diabetes<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| In-stent Late Loss (LL) | In-stent minimal lumen diameter (MLD) post-procedure minus (-) in-stent MLD at follow-up | 270 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Device Success (Per-lesion) | Successful delivery and deployment of the study stent (in overlapping stent setting a successful delivery and deployment of the first and second study stent) at the intended target lesion and successful withdrawal of the stent delivery system with attainment of final residual stenosis of less than 50% of the target lesion by quantitative coronary angiography (QCA) (by visual estimation if QCA unavailable), without use of a device outside the assigned treatment strategy. | immediately post-procedure | 
| Clinical Procedure Success (Per-patient) | Successful delivery and deployment of the study stent or stents at the intended target lesion and successful withdrawal of the stent delivery system with attainment of final residual stenosis of less than 50% of the target lesion by quantitative coronary angiography (QCA) (by visual estimation if QCA unavailable) and/or using any adjunctive device without the occurrence of cardiac death, MI attributed to the target vessel and/or CI-TLR during the hospital stay with a maximum of first seven days post index procedure. In multiple lesion setting each lesion must meet clinical procedure success. | immediately post-procedure | 
| In-segment Late Loss | In-segment minimal lumen diameter (MLD) post-procedure minus (-) in segment MLD at follow-up | 270 days | 
| Proximal Late Loss | Proximal Minimum Lumen Diameter (MLD) post-procedure minus proximal MLD at follow-up | 270 day | 
| Distal Late Loss | Distal Minimum Lumen Diameter (MLD) post-procedure minus distal MLD at follow-up | 270 days | 
| In-stent Angiographic Binary Restenosis Rate | Percent of patients with a follow-up percent diameter stenosis of ≥ 50% per QCA. | 270 days | 
| In-segment Angiographic Binary Restenosis Rate | Percent of patients with a follow-up percent diameter stenosis of ≥ 50% per QCA. | 270 days | 
| In-stent Percent Diameter Stenosis (% DS) | This number represents the average of percent diameter stenosis found on examination of all the lesions analyzed. This value calculated as 100 * (1 - minimum lumen diameter/reference vessel diameter) (MLD/RVD) using the mean values from two orthogonal views (when possible) by QCA. | 270 days | 
| In-segment Percent Diameter Stenosis (% DS) | This number represents the average of percent diameter stenosis found on examination of all the lesions analyzed. This value calculated as 100 * (1 - MLD/RVD) using the mean values from two orthogonal views (when possible) by QCA. | 270 days | 
| Adjudicated Stent Thrombosis (Confirmed/Definite, Probable, Possible) | The Clinical Event Committee will adjudicate the events according to the definitions developed by the Academic Research Consortium (ARC), as published in Circulation (Cutlip, D.E., et al., Clinical End Points in Coronary Stent Trials: A Case for Standardized Definitions. Circulation, 2007. 115: p. 2344-2351.) Stent thrombosis was defined according to the ARC guidelines as follows: definite: acute coronary syndrome and angiographic or pathological confirmation of stent thrombosis; probable: unexplained death ≤30 days or any MI that is related to acute ischemia in the territory of the implanted stent without angiographic confirmation of stent thrombosis; and possible: unexplained death >30 days after stent placement. | 0 to 37 days | 
| Adjudicated Stent Thrombosis (Confirmed/Definite, Probable, Possible) | The Clinical Event Committee will adjudicate the events according to the definitions developed by the Academic Research Consortium (ARC), as published in Circulation (Cutlip, D.E., et al., Clinical End Points in Coronary Stent Trials: A Case for Standardized Definitions. Circulation, 2007. 115: p. 2344-2351.) Stent thrombosis was defined according to the ARC guidelines as follows: definite: acute coronary syndrome and angiographic or pathological confirmation of stent thrombosis; probable: unexplained death ≤30 days or any MI that is related to acute ischemia in the territory of the implanted stent without angiographic confirmation of stent thrombosis; and possible: unexplained death >30 days after stent placement. | 254 days | 
| Adjudicated Stent Thrombosis (Confirmed/Definite, Probable, Possible) | The Clinical Event Committee will adjudicate the events according to the definitions developed by the Academic Research Consortium (ARC), as published in Circulation (Cutlip, D.E., et al., Clinical End Points in Coronary Stent Trials: A Case for Standardized Definitions. Circulation, 2007. 115: p. 2344-2351.) Stent thrombosis was defined according to the ARC guidelines as follows: definite: acute coronary syndrome and angiographic or pathological confirmation of stent thrombosis; probable: unexplained death ≤30 days or any MI that is related to acute ischemia in the territory of the implanted stent without angiographic confirmation of stent thrombosis; and possible: unexplained death >30 days after stent placement. | 365 days | 
| Adjudicated Revascularizations (Target Lesion Revascularization (TLR)/ Target Vessel Revascularization (TVR)/Any Revascularization) Both Clinically-indicated and Not Clinically-indicated. | TLR is defined as any repeat percutaneous intervention of the target lesion or bypass surgery of the target vessel performed for restenosis or other complication of the target lesion. The target lesion was defined as the treated segment from 5 mm proximal and 5 mm distal to the stent. TVR is defined as any repeat percutaneous intervention or surgical bypass of any segment of the target vessel. The target vessel was defined as the entire major coronary vessel proximal and distal to the target lesion, including upstream and downstream branches and the target lesion itself. A revascularization is considered clinically indicated if angiography at follow-up shows a %DS ≥ 50% and if one of the following occurs: history of recurrent angina pectoris due to the target vessel; signs of ischemia at rest or during exercise test due to target vessel; abnormal results of any invasive diagnostic test; TLR or TVR with a % DS ≥ 70% even in the absence of the above mentioned ischemic signs. | 37 days | 
| Adjudicated Revascularizations (Target Lesion Revascularization (TLR)/ Target Vessel Revascularization (TVR)/Any Revascularization) Both Clinically-indicated and Not Clinically-indicated. | TLR is defined as any repeat percutaneous intervention of the target lesion or bypass surgery of the target vessel performed for restenosis or other complication of the target lesion. The target lesion was defined as the treated segment from 5 mm proximal and 5 mm distal to the stent. TVR is defined as any repeat percutaneous intervention or surgical bypass of any segment of the target vessel. The target vessel was defined as the entire major coronary vessel proximal and distal to the target lesion, including upstream and downstream branches and the target lesion itself. A revascularization is considered clinically indicated if angiography at follow-up shows a %DS ≥ 50% and if one of the following occurs: history of recurrent angina pectoris due to the target vessel; signs of ischemia at rest or during exercise test due to target vessel; abnormal results of any invasive diagnostic test; TLR or TVR with a % DS ≥ 70% even in the absence of the above mentioned ischemic signs. | 254 days | 
| Adjudicated Revascularizations (Target Lesion Revascularization (TLR)/ Target Vessel Revascularization (TVR)/Any Revascularization) Both Clinically-indicated and Not Clinically-indicated. | TLR is defined as any repeat percutaneous intervention of the target lesion or bypass surgery of the target vessel performed for restenosis or other complication of the target lesion. The target lesion was defined as the treated segment from 5 mm proximal and 5 mm distal to the stent. TVR is defined as any repeat percutaneous intervention or surgical bypass of any segment of the target vessel. The target vessel was defined as the entire major coronary vessel proximal and distal to the target lesion, including upstream and downstream branches and the target lesion itself. A revascularization is considered clinically indicated if angiography at follow-up shows a %DS ≥ 50% and if one of the following occurs: history of recurrent angina pectoris due to the target vessel; signs of ischemia at rest or during exercise test due to target vessel; abnormal results of any invasive diagnostic test; TLR or TVR with a % DS ≥ 70% even in the absence of the above mentioned ischemic signs. | 393 days | 
| Adjudicated Composite Endpoint of Cardiac Death, Myocardial Infarction (MI) Attributed to the Target Vessel and Clinical-indicated Target Lesion Revascularization (CI-TLR) | Cardiac death: Any death due to proximate cardiac cause (eg, myocardial infarction, low-output failure, fatal arrhythmia), unwitnessed death and death of unknown cause, and all procedure related deaths, including those related to concomitant treatment, will be classified as cardiac death. MI- due to target vessel: All infarcts that cannot be clearly attributed to a vessel other than the target vessel will be considered related to the target vessel. Clinical-indicated Target Lesion Revascularization (CI-TLR): TLR with evidence of diameter stenosis ≥ 50% determined by QCA; or in the case of any one of the following: new recurrent history of angina pectoris, ischemic signs, abnormal results in diagnostic tests, or TLR >=70% in the absence of the above signs. | 37 days | 
| Adjudicated Composite Endpoint of Cardiac Death, Myocardial Infarction (MI) Attributed to the Target Vessel and Clinical-indicated Target Lesion Revascularization (CI-TLR) | Cardiac death: Any death due to proximate cardiac cause (eg, myocardial infarction, low-output failure, fatal arrhythmia), unwitnessed death and death of unknown cause, and all procedure related deaths, including those related to concomitant treatment, will be classified as cardiac death. MI- due to target vessel: All infarcts that cannot be clearly attributed to a vessel other than the target vessel will be considered related to the target vessel. Clinical-indicated Target Lesion Revascularization (CI-TLR): TLR with evidence of diameter stenosis ≥ 50% determined by QCA; or in the case of any one of the following: new recurrent history of angina pectoris, ischemic signs, abnormal results in diagnostic tests, or TLR >=70% in the absence of the above signs. | 254 days | 
| Adjudicated Composite Endpoint of Cardiac Death, Myocardial Infarction (MI) Attributed to the Target Vessel and Clinical-indicated Target Lesion Revascularization (CI-TLR) | Cardiac death: Any death due to proximate cardiac cause (eg, myocardial infarction, low-output failure, fatal arrhythmia), unwitnessed death and death of unknown cause, and all procedure related deaths, including those related to concomitant treatment, will be classified as cardiac death. MI- due to target vessel: All infarcts that cannot be clearly attributed to a vessel other than the target vessel will be considered related to the target vessel. Clinical-indicated Target Lesion Revascularization (CI-TLR): TLR with evidence of diameter stenosis ≥ 50% determined by QCA; or in the case of any one of the following: new recurrent history of angina pectoris, ischemic signs, abnormal results in diagnostic tests, or TLR >=70% in the absence of the above signs. | 393 days | 
| Adjudicated Composite Endpoint of All Death, MI and Target Vessel Revascularization (TVR) | Death defined by the Academic Research Consortium is as follows: All death is considered to be cardiac death unless an unequivocal noncardiac cause can be established. Specifically, any unexpected death even in patients with coexisting potentially fatal noncardiac disease (eg, cancer, infection) should be classified as cardiac. Myocardial infarction: Myocardial Infarction Classification and Criteria for Diagnosis as defined by the Academic Research Consortium. Target Vessel Revascularization (TVR): Target vessel revascularization 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. | 37 days | 
| Adjudicated Composite Endpoint of All Death, MI and Target Vessel Revascularization (TVR) | Death defined by the Academic Research Consortium is as follows: All death is considered to be cardiac death unless an unequivocal noncardiac cause can be established. Specifically, any unexpected death even in patients with coexisting potentially fatal noncardiac disease (eg, cancer, infection) should be classified as cardiac. Myocardial infarction: Myocardial Infarction Classification and Criteria for Diagnosis as defined by the Academic Research Consortium. Target Vessel Revascularization (TVR): Target vessel revascularization 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. | 254 days | 
| Adjudicated Composite Endpoint of All Death, MI and Target Vessel Revascularization (TVR) | Death defined by the Academic Research Consortium is as follows: All death is considered to be cardiac death unless an unequivocal noncardiac cause can be established. Specifically, any unexpected death even in patients with coexisting potentially fatal noncardiac disease (eg, cancer, infection) should be classified as cardiac. Myocardial infarction: Myocardial Infarction Classification and Criteria for Diagnosis as defined by the Academic Research Consortium. Target Vessel Revascularization (TVR): Target vessel revascularization 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. | 393 days | 
| Adjudicated Composite Endpoint of All Death, Any Myocardial Infarction (MI) and Any Revascularization (TLR/TVR/Non-TVR) | Death defined by the Academic Research Consortium is as follows: All death is considered to be cardiac death unless an unequivocal noncardiac cause can be established. MI- due to target vessel: All infarcts that cannot be clearly attributed to a vessel other than the target vessel will be considered related to the target vessel. Any revascularization: TLR or TVR or non-TVR | 37 days | 
| Adjudicated Composite Endpoint of All Death, Any Myocardial Infarction (MI) and Any Revascularization (TLR/TVR/Non TVR) | Death defined by the Academic Research Consortium is as follows: All death is considered to be cardiac death unless an unequivocal noncardiac cause can be established. MI- due to target vessel: All infarcts that cannot be clearly attributed to a vessel other than the target vessel will be considered related to the target vessel. Any revascularization: TLR or TVR or non-TVR | 254 days | 
| Adjudicated Composite Endpoint of All Death, Any Myocardial Infarction (MI) and Any Revascularization (TLR/TVR/Non TVR) | Death defined by the Academic Research Consortium is as follows: All death is considered to be cardiac death unless an unequivocal noncardiac cause can be established. MI- due to target vessel: All infarcts that cannot be clearly attributed to a vessel other than the target vessel will be considered related to the target vessel. Any revascularization: TLR or TVR or non-TVR | 393 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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drug eluting stents, stents, Angioplasty, coronary artery disease, total coronary occlusion, coronary artery restenosis, stent thrombosis, vascular disease, myocardial ischemia, coronary artery stenosis