SPIRIT IV Clinical Trial: Clinical Evaluation of the XIENCE V® Everolimus Eluting Coronary Stent System

SPIRIT IV Clinical Trial: Clinical Evaluation of the XIENCE V® Everolimus Eluting Coronary Stent System in the Treatment of Subjects With de Novo Native Coronary Artery Lesions

The purpose of the SPIRIT IV Clinical Trial is to continue to evaluate the safety and efficacy of the XIENCE V® Everolimus Eluting Coronary Stent System (XIENCE V®). The XIENCE V® arm will be compared to an active control, represented by the FDA-approved TAXUS® EXPRESS2™ Paclitaxel-Eluting Coronary Stent System (TAXUS®), commercially available from Boston Scientific.

TAXUS® EXPRESS2™ Paclitaxel Eluting Coronary Stent System is manufactured by Boston Scientific.

The completion of the SPIRIT IV clinical trial at three years is justified by the consistent long-term clinical evidence supporting the safety and efficacy of the XIENCE V EECSS in complex, real-world patients across multiple geographies. As SPIRIT IV was designed as a continued access trial, completing the clinical follow-up at the three-year visit does not conflict with any FDA requirements. Abbott Vascular is committed to providing clinical outcomes through three years. The clinical evidence provided from across multiple geographies, in complex populations thus supports Abbott Vascular's proposal to complete the SPIRIT IV RCT at the three-year clinical follow-up.

The SPIRIT IV Clinical Trial is a randomized, active-controlled, single-blinded, multicenter clinical trial in the US that will enroll approximately 3,690 subjects (2:1 randomization XIENCE V®: TAXUS®). The trial allows the treatment of up to three de novo native coronary artery lesions, maximum of two lesion per epicardial vessel, with reference vessel diameters (RVD) ≥ 2.5 mm to ≤ 4.25 mm and lesion lengths ≤ 28 mm. (NOTE: RVD ≥ 2.5 mm to ≤ 3.75 mm until 4.0 mm TAXUS® is commercially available). All subjects will be screened per the protocol inclusion and exclusion criteria and enrolled subjects will have clinical follow-up at 30, 180, and 270 days and 1, 2, and 3 years.

General Inclusion Criteria:

• Subject must be at least 18 years of age
• Subject is able to verbally confirm understanding of risks, benefits and treatment alternatives of receiving XIENCE V® and he/she or his/her legally authorized representative provides written informed consent prior to any study related procedure
• 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:

• Target lesion(s) must be located in a native coronary artery with visually estimated diameter of ≥2.5 mm to ≤4.25 mm and treatment of up to a three de novo target lesions, maximum of two de novo target lesions per epicardical vessel. (NOTE: RVD ≥2.5 mm to ≤3.75 mm until 4.0 mm TAXUS® is commercially available)
• Target lesion(s) must measure ≤28 mm in length by visual estimation(≥3 mm of non-diseased tissue on either side of the target lesion should be covered by the study stent)
• If more than one target lesion will be treated, the RVD and lesion length of each must meet the above criteria
• If more than one target lesion will be treated, the RVD and lesion length of each must meet the above criteria
• The target lesion(s) must be in a major artery or branch with a visually estimated stenosis of ≥ 50% and < 100% with a TIMI flow of ≥ 1
• Non-study, percutaneous intervention for lesions in a target vessel (including side branches) is allowed if done ≥ 9 months prior to the index procedure
• Non-study percutaneous intervention for lesions in a non-target vessel involving:
• Successful and uncomplicated (visually estimated diameter stenosis < 50%, TIMI Grade 3 flow, no ECG changes, prolonged chest pain, or angiographic complications) bare-metal stent, balloon dilatation, cutting balloon, atherectomy, thrombectomy, and laser treatments are allowed if done ≥ 24 hours prior to the index procedure or during (before randomization) the index procedure. For interventions done within 24 to 48 hours prior to the index procedure, CK and CK-MB must be assessed to be < 2 times the upper limit of normal at the time of the index procedure. NOTE: Procedures within the 24 hour period preceding the index procedure are not permitted
• Unsuccessful or complicated bare-metal stent, balloon dilatation, cutting balloon, atherectomy, thrombectomy, and laser treatments are allowed if done ≥ 30 days prior to the index procedure
• Drug-eluting stent treatment is allowed if done ≥ 90 days prior to the index procedure
• Non-study, percutaneous interventions for lesion(s) in a target vessel (including side branches) or non-target vessel are allowed if done ≥ 9 months after the index procedure

General 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 within normal limits at the time of procedure
• The subject is currently experiencing clinical symptoms consistent with AMI
• Subject has current unstable arrhythmias
• Subject has a known left ventricular ejection fraction (LVEF) < 30%
• Subject has received a heart transplant or any other organ transplant or is on a waiting list for any organ transplant
• Subject is receiving or scheduled to receive anticancer therapy for malignancy within 30 days prior to or after the procedure
• Subject is receiving immunosuppression therapy, or has known serious immunosuppressive disease (e.g., human immunodeficiency virus), or has severe autoimmune disease that requires chronic immunosuppressive therapy (e.g., systemic lupus erythematosus, etc.)
• Subject is receiving or is scheduled to receive chronic anticoagulation therapy (e.g., heparin, coumadin)
• Subject has a known hypersensitivity or contraindication to aspirin, both heparin and bivalirudin, both clopidogrel and ticlopidine, everolimus, cobalt, chromium, nickel, tungsten, acrylic and fluoro polymers or contrast sensitivity that cannot be adequately pre-medicated
• Elective surgery that will require discontinuing either aspirin or clopidogrel is planned within the first 9 months after the procedure
• Subject 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)
• Subject has known renal insufficiency (e.g., serum creatinine level of > 2.5 mg/dL or subject on dialysis)
• Subject has a history of bleeding diathesis or coagulopathy or will refuse blood transfusions
• Subject has had a cerebrovascular accident (CVA) or transient ischemic neurological attack (TIA) within the past six months
• Subject has had a significant GI or urinary bleed within the past six months
• Subject has extensive peripheral vascular disease that precludes safe 6 French sheath insertion
• Subject 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 life expectancy of less than one year
• Subject is already participating in another clinical study that has not yet reached 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 and effective contraception must be used up to 1 year following the index procedure)
• Angiographic Exclusion Criteria
• The target lesion(s) meets any of the following criteria:
• Left main coronary artery location including left main ostial location (NOTE: RCA-aorto-ostial lesions are not excluded)
• Located within 2 mm of the origin of the LAD or LCX
• Located within an arterial or saphenous vein graft or distal to a diseased (vessel irregularity per angiogram and any visually estimated diameter stenosis > 20%) arterial or saphenous vein graft
• Involves a bifurcation in which the side branch is ≥ 2 mm in diameter AND the ostium of the side branch is > 50% stenosed by visual estimation
• Involves a side branch requiring pre-dilatation
• Total occlusion (TIMI flow 0) prior to wire crossing
• Excessive tortuosity proximal to or within the lesion
• Extreme angulation (≥ 90º) proximal to or within the lesion
• Heavy calcification
• Restenotic from previous intervention
• Subject has received brachytherapy in any epicardial vessel (including side branches)
• The target vessel contains thrombus
• Another clinically significant lesion in the target vessel is present that requires or has a high probability of requiring PCI during the index procedure
• Another lesion in a target or non-target vessel (including all side branches) is present that requires or has a high probability of requiring PCI within 9 months after the index procedure