EXecutive RCT: Evaluating XIENCE V® in a Multi Vessel Disease

EXecutive Randomized Controlled Trial (RCT): XIENCE V® Everolimus Eluting Coronary Stent System (XIENCE V® EECSS) in the Treatment of the Specific Setting of Patients With Multi-vessel Coronary Artery Disease.

The purpose of this two part study is the assessment of the performance of the XIENCE V® Everolimus Eluting Coronary Stent System (XIENCE V® EECSS) in the treatment of the specific setting of patients with Multi-Vessel Coronary Artery Disease (MVD).

This is a clinical evaluation of the XIENCE V® everolimus eluting coronary stent system as a revascularization treatment of patients with multi-vessel coronary artery disease (MVD-CAD).

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 consistently lower than the comparator arm of each study.

The post approval EXECUTIVE 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 EXECUTIVE trial.

The study is composed of two parts:

A Registry, outlined in a separate posting and the Randomized Control Trial (RCT) portion of this study, which is as follows:

-A randomized group of patients aimed at assessing the angiographic efficacy of the XIENCE V® Everolimus Eluting Coronary Stent System (XIENCE V® EECSS) compared to the TAXUS® Liberté™ Paclitaxel Eluting Coronary Stent System.

Inclusion Criteria:

1. Patient must be at least 18 years of age
2. Patient is 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
3. Patient has been diagnosed a MVD, as documented by coronary angiography, i.e. presenting a severe stenosis (>50%) amenable to PCI in at least 2 major epicardial vessels or their principal bifurcation branches (diagonal or obtuse marginal)
4. Patient 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)
5. Patient must be an acceptable candidate for coronary artery bypass graft (CABG) surgery
6. Patient must agree to undergo all protocol-required follow-up examinations.

Angiographic Inclusion Criteria

1. Patients may receive up to 4 planned XIENCE V® EECSS stents, depending on the number of vessels treated and their respective lesion length. When multiple lesions are present in one or more main coronary branches, complete revascularization should be attempted with the implantation of a maximum of 4 planned stents
2. Target lesions must be de novo lesions (no prior stent implant, no prior brachytherapy)
3. Target vessel reference diameter must be between 2.5 mm and 4.0 mm by visual estimate
4. Target lesion < or = 28 mm in length by visual estimation
5. Target lesions must be in a major artery or its principal branches (diagonal or obtuse marginal) with a visually estimated stenosis of > or = 50%
6. Two lesions in a single main coronary artery or its branches do not constitute a MVD situation, therefore this type of patient must not be enrolled

Exclusion Criteria:

1. Patient has had a known diagnosis of acute myocardial infarction (AMI) within 72 hours preceding the index procedure (non-procedural/spontaneous MI, CK-MB > or = to 2 times upper limit of normal) and CK and CK-MB have not returned within normal limits at the time of procedure
2. Patient has current unstable arrhythmias
3. Patient has a known left ventricular ejection fraction (LVEF) <30%
4. Patient has received a heart transplant or any other organ transplant or is on a waiting list for any organ transplant
5. Patient is receiving or scheduled to receive chemotherapy or radiation therapy within 30 days prior to or after the procedure.
6. Patient is receiving immunosuppression therapy or has known immunosuppressive or autoimmune disease (e.g. human immunodeficiency virus, systemic lupus erythematosus etc.)
7. Patient is receiving chronic anticoagulation therapy (e.g. coumadin)
8. Patient has a known hypersensitivity or contraindication to aspirin, paclitaxel, either heparin or bivalirudin, clopidogrel or ticlopidine, everolimus, cobalt, chromium, nickel, tungsten, acrylic and fluoro polymers or contrast sensitivity that cannot be adequately pre-medicated
9. Elective surgery is planned within the first 9 months (+/- 14 days) after the procedure that will require discontinuing either aspirin or clopidogrel
10. Patient has a platelet count <100,000 cells/mm3 or >700,000 cells/mm3, a WBC of <3,000 cells/mm3, or documented or suspected liver disease (including laboratory evidence of hepatitis)
11. Patient has known renal insufficiency (e.g., serum creatinine level of more than 2.5 mg/dl, patient on dialysis)
12. Patient has a history of bleeding diathesis or coagulopathy or will refuse blood transfusions
13. Patient has had a cerebrovascular accident (CVA) or transient ischemic neurological attack (TIA) within the past six months
14. Patient has had a significant GI or urinary bleed within the past six months
15. Patient has other medical illness (e.g., cancer or congestive heart failure) 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)
16. Patient is already participating in another investigational use device or drug study or has completed the follow-up phase of another study within the last 30 days.

Angiographic Exclusion Criteria

1. Target lesion meets any of the following criteria:

   • Left main location
   • 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)
   • Heavy calcification

2. The patient may need more than 4 planned stents. Bailout stents are allowed but must be of the same type as randomization stent.