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

Phase 3

Completed

Conditions: Coronary Artery Disease

Interventions: Device: XIENCE V® Everolimus Eluting Coronary Stent
Device: TAXUS™ EXPRESS2™ Paclitaxel Eluting Coronary Stent

Registration Number: NCT00307047

Lead Sponsor: Abbott Medical Devices

Brief Summary: 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.

Detailed Description: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 3687

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
XIENCE V®	XIENCE V® Everolimus Eluting Coronary Stent	-
TAXUS™ EXPRESS2™	TAXUS™ EXPRESS2™ Paclitaxel Eluting Coronary Stent	-

Primary Outcome Measures

Name	Time	Method
Ischemia Driven Target Lesion Failure (TLF)	1 year	Percentage of participants with the determination of TLF. TLF is the composite of cardiac death, target vessel myocardial infarction, and ischemic driven target lesion revascularization (TLR).

Secondary Outcome Measures

Name	Time	Method
Ischemia Driven Target Vessel Failure (TVF)	3 years	Defined as the composite endpoint comprised of cardiac death (CD), myocardial infarction (MI), TLR, and TVR
Ischemia Driven Target Lesion Revascularization (TLR)	3 years	Revascularization of a target lesion associated with any of the following: * positive functional ischemia study * ischemic symptoms and angiographic minimal lumen diameter stenosis ≥ 50% by core laboratory quantitative coronary angiography (QCA) * angiographic diameter stenosis ≥ 70% by core laboratory QCA without either ischemic symptoms or a positive functional study
Ischemia Driven Target Vessel Revascularization (TVR)	3 years	Revascularization of a lesion within the target vessel associated with any of the following: * positive functional ischemia study * ischemic symptoms and an angiographic minimal lumen diameter stenosis ≥ 50% by core laboratory quantitative coronary angiography (QCA) * angiographic diameter stenosis ≥ 70% by core laboratory QCA without either ischemic symptoms or a positive functional study
Ischemia Driven Major Adverse Cardiac Events (MACE)	3 years	Patients determined to have had a MACE event, defined as one of the following events: Cardiac death, myocardial infarction, and TLR
Acute Success (Clinical Device)	Acute: At time of index procedure	Successful delivery and deployment of the first implanted study stent (in overlapping stent setting a successful delivery and deployment of the first and second study 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 QCA (by visual estimation if QCA unavailable). Bailout subjects will be included as device success only if the above criteria for clinical device are met.
Acute Success (Clinical Procedure)	Acute: At time of index procedure	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 QCA (by visual estimation if QCA unavailable) and/or using any adjunctive device without the occurrence of major adverse cardiac event (MACE) during the hospital stay with a maximum of first seven days following the index procedure. In multiple lesion setting all lesions must meet clinical procedure success.
All Myocardial Infarction (MI)	30 days
All MI	3 years
All Cause Mortality	3 years
Composite Endpoint of All Deaths, All MI, All Revascularizations (DMR)	3 years
Definite + Probable Stent Thrombosis Rate Based on Academic Research Consortium (ARC) Definition	0-30 days	ARC: Academic Research Consortium-defines ST as a cumulative value at the different time points and with the different seperate time points. Time 0 is defined as the time point after the guiding catheter has been removed. Acute\: 0-24 hours post implantation Subacute\: \>24 hours-30 days post Late†: 30 days-1 year post Very late stent thrombosis†: \>1 year post \* Acute/subacute can also be replaced by early ST. Early ST (0-30 days) is currently used in the community. † Including "primary" as well as "secondary" late ST; "secondary" late ST is after a target segment revascularization.
Definite + Probable Stent Thrombosis Rate Based on ARC Definition	0-1123 days	ARC: Academic Research Consortium-defines ST as a cumulative value at the different time points and with the different seperate time points. Time 0 is defined as the time point after the guiding catheter has been removed. Acute\: 0-24 hours post implantation Subacute\: \>24 hours-30 days post Late†: 30 days-1 year post Very late stent thrombosis†: \>1 year post \* Acute/subacute can also be replaced by early ST. Early ST (0-30 days) is currently used in the community. † Including "primary" as well as "secondary" late ST; "secondary" late ST is after a target segment revascularization.
Protocol Defined Stent Thrombosis Rate	0-1123 days	ST will be categorized as acute (≤ 1day), subacute (\>1 day to ≤ 30 days) and late (\>30 days) and will be defined as any of the following: * Clinical presentation of acute coronary syndrome with angiographic evidence of ST * In the absence of angiography, any unexplained death, or acute MI (S-T segment elevation or new Q-wave)\* in the distribution of the target lesion within 30 days \*(Non-specific S-T/T changes, and cardiac enzyme elevations do not suffice) Any thromboses that occur less than 30 days after the index procedure will not be counted as restenosis.
Cardiac Death or Target Vessel MI Rate	3 years
Ischemia Driven Target Lesion Failure (TLF)	3 years	Percentage of participants with the determination of TLF. TLF is the composite of cardiac death, target vessel myocardial infarction, and ischemic driven target lesion revascularization (TLR).

Trial Locations

Locations (65): Wake Medical Center
🇺🇸
Raleigh, North Carolina, United States
Union Memorial Hospital
🇺🇸
Baltimore, Maryland, United States
Geisinger Medical Center
🇺🇸
Danville, Pennsylvania, United States
Northern Michigan Hospital
🇺🇸
Petoskey, Michigan, United States
Bay Regional Medical Center
🇺🇸
Bay City, Michigan, United States
Oakwood Hospital and Medical Center
🇺🇸
Dearborn, Michigan, United States
The Miriam Hospital
🇺🇸
Providence, Rhode Island, United States
Sisters of Charity Providence Hospitals
🇺🇸
Columbia, South Carolina, United States
Fletcher Allen Health Care
🇺🇸
Burlington, Vermont, United States
Brigham and Women's Hospital
🇺🇸
Boston, Massachusetts, United States
The Heart Center of Indiana
🇺🇸
Indianapolis, Indiana, United States
Poudre Valley Hospital
🇺🇸
Fort Collins, Colorado, United States
Providence St. Vincent Medical Center
🇺🇸
Portland, Oregon, United States
Vanderbilt Vniversity Medical Center
🇺🇸
Nashville, Tennessee, United States
Mercy General Hospital
🇺🇸
Sacramento, California, United States
Iowa Heart Center P.C.
🇺🇸
Des Moines, Iowa, United States
Central Baptist Hospital
🇺🇸
Lexington, Kentucky, United States
Jewish Hospital
🇺🇸
Louisville, Kentucky, United States
The Medical Center of Aurora
🇺🇸
Aurora, Colorado, United States
St. Luke's Medical Center - Milwaukee
🇺🇸
Milwaukee, Wisconsin, United States
EMH Regional Medical Center
🇺🇸
Elyria, Ohio, United States
UPMC Presbyterian Hospital
🇺🇸
Pittsburgh, Pennsylvania, United States
Plaza Medical Center of Fort Worth
🇺🇸
Fort Worth, Texas, United States
Millard Fillmore Hospital
🇺🇸
Buffalo, New York, United States
Columbia University Medical Center
🇺🇸
New York, New York, United States
Good Samaritan Hospital - LA
🇺🇸
Los Angeles, California, United States
St. Joseph's Hospital Health Center
🇺🇸
Syracuse, New York, United States
The Christ Hospital
🇺🇸
Cincinnati, Ohio, United States
Arkansas Heart Hospital
🇺🇸
Little Rock, Arkansas, United States
New York Presbyterian Hospital-Cornell
🇺🇸
New York City, New York, United States
Nebraska Heart Hospital
🇺🇸
Lincoln, Nebraska, United States
Stony Brook Hospital and Medical Center
🇺🇸
Stony Brook, New York, United States
Sentara Norfolk General
🇺🇸
Norfolk, Virginia, United States
The Valley Hospital
🇺🇸
Pomona, New York, United States
San Diego Cardiovascular Associates
🇺🇸
La Jolla, California, United States
St. Francis Hospital and Health Centers
🇺🇸
Indianapolis, Indiana, United States
St. Patrick Hospital
🇺🇸
Missoula, Montana, United States
Pitt County Memorial Hospital
🇺🇸
Greenville, North Carolina, United States
Presbyterian Hospital - Charlotte
🇺🇸
Charlotte, North Carolina, United States
Dartmouth Hitchock Medical Center
🇺🇸
Lebanon, New Hampshire, United States
Riverside Methodist Hospital
🇺🇸
Columbus, Ohio, United States
Inova Fairfax Hospital
🇺🇸
Fairfax, California, United States
Scripps Memorial Hospital
🇺🇸
La Jolla, California, United States
Scottsdale Healthcare
🇺🇸
Scottsdale, Arizona, United States
Sutter Medical Center of Santa Rosa
🇺🇸
Santa Rosa, California, United States
Washington Hospital Center
🇺🇸
Washington, District of Columbia, United States
Sarasota Memorial Hospital
🇺🇸
Sarasota, Florida, United States
Sacred Heart Hospital
🇺🇸
Pensacola, Florida, United States
University of Kansas Hospital
🇺🇸
Kansas City, Kansas, United States
Johns Hopkins Hospital
🇺🇸
Baltimore, Maryland, United States
Maine Medical Center
🇺🇸
Portland, Maine, United States
St. Joseph Medical Center
🇺🇸
Towson, Maryland, United States
Saint Vincent Hospital
🇺🇸
Worcester, Massachusetts, United States
UMass Memorial Medical Center
🇺🇸
Worcester, Massachusetts, United States
Ingham Regional Medical Center
🇺🇸
Lansing, Michigan, United States
Spectrum Health Hospital
🇺🇸
Grand Rapids, Michigan, United States
Borgess Medical Center
🇺🇸
Kalamazoo, Michigan, United States
Forsyth Medical Center
🇺🇸
Winston-Salem, North Carolina, United States
Washington Adventist Hospital
🇺🇸
Takoma Park, Maryland, United States
St. Luke's Hospital
🇺🇸
Kansas City, Missouri, United States
Research Medical Center
🇺🇸
Kansas City, Missouri, United States
Wake Forest University Baptist Medical Center
🇺🇸
Winston-Salem, North Carolina, United States
Medical University of South Carolina (MUSC)
🇺🇸
Charleston, South Carolina, United States
St. Francis Health System
🇺🇸
Greenville, South Carolina, United States
Rhode Island Hospital
🇺🇸
Providence, Rhode Island, United States