Randomized Trial Evaluating Slow-Release Formulation TAXUS Paclitaxel-Eluting Coronary Stents to Treat De Novo Coronary Lesions

TAXUS V: De Novo Lesion: A Randomized, Double-blind Trial to Assess TAXUS Paclitaxel-Eluting Coronary Stents, SR Formulation, in the Treatment of De Novo Coronary Lesions

The primary objective of this study is to further evaluate the safety and effectiveness of the TAXUS Express2 Paclitaxel-Eluting Coronary Stent System in long lesion lengths, small and large vessel diameters and with multiple overlapping stents in the treatment of de novo coronary artery lesions

Study Overview

• Status: Completed
• Conditions: Coronary Stenosis
• Intervention / Treatment: Device: Express2; Device: TAXUS Paclitaxel-Eluting Coronary Stent, Slow-Formulation

Detailed Description

The primary endpoint is the incidence rate of TVR through 9 months post index procedure. In this protocol, TVR must be ischemia driven, based on the presence of symptoms, positive functional testing or Quantitative Coronary Angiography (QCA) severity of restenosis.

Secondary endpoints include the following:

• Incidence rates of composite MACE and the individual components of MACE assessed at discharge, 1, 4 and 9 months post index procedure and annually for 5 years (i.e., 1, 2, 3, 4 and 5 years post index procedure).
• Stent thrombosis rate.
• TVF.
• Clinical procedural success and technical success.
• Binary restenosis rate.

• Additional angiographic endpoints to be measured in all patients with 9 month angiographic follow-up include:

  • Absolute lesion length
  • Reference Vessel Diameter (RVD)
  • Minimum Lumen Diameter (MLD)
  • Percent diameter stenosis (% DS)
  • Acute gain
  • Late loss
  • Loss index
  • Patterns of recurrent restenosis, including edge effect
  • Coronary aneurysm

• IVUS Substudy

  • Identification of potential safety issues, i.e., incomplete stent apposition.
  • change in neointimal volume from post procedure to follow-up
  • change in MLD within stent
  • minimum lumen area (MLA) within stent
  • lumen, plaque and vessel measurements at the stent edges (outside stent)

• Study Type: Interventional
• Enrollment (Actual): 1108
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35211
      • Baptist Medical Center Princeton
    • Birmingham, Alabama, United States, 35213
      • Cardiovascular Associates PC/Baptist Medical Center Montclair
    • Birmingham, Alabama, United States, 35294
      • UAB Interventional Cardiology
  • Arizona
    • Phoenix, Arizona, United States, 85006
      • Arizona Heart Institute and Hospital
  • California
    • La Jolla, California, United States, 92037
      • Scripps Memorial Hospital LaJolla
    • Sacramento, California, United States, 95817
      • University of California Davis Medical Center
    • Sacramento, California, United States, 95819
      • Mercy General Hospital
    • Stanford, California, United States, 94305
      • Stanford Medical Center
  • Colorado
    • Aurora, Colorado, United States, 80012
      • Aurora Denver Cardiology
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Washington Hospital Center
  • Florida
    • Atlantis, Florida, United States, 33462
      • Palm Beach Heart Research Institute, LLC
    • Clearwater, Florida, United States, 33756
      • Clearwater Cardiovascular and Interventional Consultants
    • Miami Beach, Florida, United States, 33137
      • Miami International Cardiology Consultants
    • Ocala, Florida, United States, 34471
      • Mediquest Research Group, Inc.
    • Orlando, Florida, United States, 32803
      • Florida Hospital
    • Safety Harbor, Florida, United States, 34695
      • The Heart & Vascular Institute Of Florida
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University Hospital
    • Atlanta, Georgia, United States, 30309
      • Piedmont Hospital
    • Atlanta, Georgia, United States, 30342
      • St. Joseph's Hospital of Atlanta
  • Illinois
    • Evanston, Illinois, United States, 60201
      • Evanston Northwestern Health Care
    • Lombard, Illinois, United States, 60148
      • Midwest Heart Foundation
  • Kansas
    • Shawnee Mission, Kansas, United States, 66204
      • Shawnee Mission Medical Center
  • Kentucky
    • Lexington, Kentucky, United States, 40503
      • Central Baptist Hospital
  • Louisiana
    • New Orleans, Louisiana, United States, 70121
      • Ochsner Clinic Foundation
  • Maine
    • Portland, Maine, United States, 04102
      • Maine Medical Center
  • Maryland
    • Takoma Park, Maryland, United States, 20912
      • Washington Adventist Hospital
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02111
      • Tufts Medical Center
    • Burlington, Massachusetts, United States, 01805
      • Lahey Clinic Hospital
    • Worcester, Massachusetts, United States, 01655
      • University of Massachusetts Memorial Medical Center
  • Michigan
    • Detroit, Michigan, United States, 48236
      • St. John's Hospital and Medical Center
    • Grand Rapids, Michigan, United States, 49503
      • Spectrum Health Hospitals
    • Petoskey, Michigan, United States, 49770
      • Cardiac & Vascular Research Center of Northern Michigan
    • Royal Oak, Michigan, United States, 48073
      • William Beaumont Hospital
  • Minnesota
    • Minneapolis, Minnesota, United States, 55407
      • Minneapolis Heart Institute
    • Rochester, Minnesota, United States, 55902
      • Mayo Clinic/Saint Mary's Hospital
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • Saint Luke's Hospital
    • St. Louis, Missouri, United States, 63110
      • Barnes Jewish Hospital
  • Nebraska
    • Lincoln, Nebraska, United States, 68526
      • Nebraska Heart Institute
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Hackensack University Medical Center
    • Newark, New Jersey, United States, 07102
      • Saint Michael's Medical Center
  • New York
    • Albany, New York, United States, 12208
      • Albany Medical Center/Capital Cardiovascular Associates
    • Buffalo, New York, United States, 14215
      • Buffalo General Hospital
    • New York, New York, United States, 10021
      • New York Presbyterian Hospital
    • New York, New York, United States, 10021
      • Lenox Hill Hospital
    • New York, New York, United States, 10029
      • Mt. Sinai Medical Center
    • New York, New York, United States, 10021
      • Columbia University Medical Center
    • Rochester, New York, United States, 14641
      • Rochester General Hospital
    • Roslyn, New York, United States, 11576
      • St. Francis Hospital
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Mid-Carolina Cardiology Research Division/Presbyterian Hospital
    • Greensboro, North Carolina, United States, 27401
      • LeBauer Cardiovascular Research Foundation
    • Raleigh, North Carolina, United States, 27610
      • Wake Heart Research
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University Health Sciences
    • Winston-Salem, North Carolina, United States, 27103
      • Forsyth Medical Center
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • The Lindner Clinical Trial Center
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation
    • Columbus, Ohio, United States, 43214
      • MidWest Cardiology Research Foundation/Riverside Methodist Hospital
    • Elyria, Ohio, United States, 44035
      • North Ohio Research, Ltd
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73120
      • Oklahoma Cardiovascular Research Group
  • Pennsylvania
    • Langhorne, Pennsylvania, United States, 19047
      • St. Mary's Medical Center
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Rhode Island Hospital
  • South Carolina
    • Columbia, South Carolina, United States, 29204
      • South Carolina Heart Center
  • Tennessee
    • Nashville, Tennessee, United States, 37205
      • St. Thomas Hospital
  • Texas
    • Austin, Texas, United States, 78745
      • South Austin Hospital/Capital Cardiovascular Specialists
    • Dallas, Texas, United States, 75246
      • Baylor University Medical Center
    • Dallas, Texas, United States, 75231
      • Cardiovascular Research Institute of Dallas
    • Houston, Texas, United States, 77030
      • University of Texas Houston Hermann Hospital
  • Utah
    • Provo, Utah, United States, 84604
      • Utah Valley Regional Medical Center
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia
    • Norfolk, Virginia, United States, 23507
      • Sentara Norfolk General Hospital
  • Washington
    • Seattle, Washington, United States, 98104
      • Swedish Medical Center
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53215
      • St. Luke's Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patient was ≥ 18 years old.
• Eligible for percutaneous coronary intervention.
• Documented stable angina pectoris.
• LVEF of greater than 25%.
• Acceptable candidate for coronary artery bypass grafting.
• Target lesion segment is located within a single native coronary vessel.
• Target lesion was de novo.
• RVD was greater than 2.25 mm and less than 4.0 mm .and patient and/or lesion fulfilled protocol defined subgroups.
• Cumulative target lesion length was greater than 10 mm and less than 46mm assessed after pre-dilatation with standard balloon or cutting balloon angioplasty, including adjacent areas of dissection that were covered.
• Target lesion diameter stenosis less than 50% before pre-dilatation .
• Vessel and lesion morphology such that the lesion was treated only with study stent(s); no planned use of commercial stents.

Exclusion Criteria:

• Known hypersensitivity to paclitaxel.
• Any previous or planned treatment with a non-study anti-restenotic drug-coated or drug-eluting coronary stent.
• Planned use of both the study stent and a non-study stent in the treatment of the target vessel.
• Previous or planned treatment with intravascular brachytherapy in the target vessel.
• Recent MI.
• CK-MB greater than 2x the local laboratory's upper limit of normal.
• Cerebrovascular accident within 6 months of randomization.
• Planned CABG ≤ 9 months post index procedure.
• Acute or chronic renal dysfunction.
• Leukopenia.
• Thrombocytopenia or thrombocytosis.
• Active peptic ulcer or active gastrointestinal bleeding, or previously active within 6 months.
• Known allergy to stainless steel.
• Any prior true anaphylactic reaction to contrast agents.
• Contraindication to ASA or to both clopidogrel and ticlopidine.
• Patient was on warfarin or it was anticipated that treatment with warfarin would have been required during any period within 6 months post the index procedure.
• Patient was or had been treated with chemotherapeutic agents within 12 months of the index procedure.
• Anticipated treatment with paclitaxel, oral rapamycin or colchicine during any period in the 9 months post index procedure.
• Male or female with known intention to procreate within 3 months post index procedure.
• Co-morbid condition(s) that could limit the patient's ability to participate in the study, limit compliance with follow-up requirements or impact the scientific integrity of the study.
• Planned surgical procedure requiring withdrawal of any anti-platelet therapy within 6 months post index procedure.
• Currently participating in another investigational drug or device study that has not completed the primary endpoint or that clinically interferes with the endpoints of this study.
• Unprotected left main coronary artery disease.
• Target lesion was ostial in location.
• Target lesion and/or target vessel proximal to the target lesion was moderately or severely calcified.
• Target lesion was located within or distal to a > 60° bend in the vessel.
• Side branch of the target lesion included ostial narrowing ≥ 50% DS and was ≥ 2.0 mm diameter.
• Target lesion was totally occluded.
• Angiographic presence of probable or definite thrombus.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm 2	Device: Express2; Coronary Stent System
Experimental: Arm 1	Device: TAXUS Paclitaxel-Eluting Coronary Stent, Slow-Formulation; Paclitaxel-Eluting Coronary Stent, Slow-Formulation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence rate of TVR through 9 months post index procedure	9 Months

Secondary Outcome Measures

Outcome Measure	Time Frame
Stent thrombosis rate	5 Years
Absolute lesion length	9 Months
Reference Vessel Diameter (RVD)	9 Months
Minimum Lumen Diameter (MLD)	9 Months
Percent diameter stenosis (% DS)	9 Months
Acute gain	9 Months
Late loss	9 Months
Loss index	9 Months
Patterns of recurrent restenosis, including edge effect	9 Months
Coronary aneurysm	9 Months
• Incidence rates of composite MACE and the individual components of MACE assessed at discharge, 1, 4 and 9 months post index procedure and annually for 5 years (i.e., 1, 2, 3, 4 and 5 years post index procedure).	5 Years
Target Vessel Failure	5 Years
Clinical procedural success and technical success	5 years
Binary restenosis rate.	5 Years
Identification of potential safety issues, i.e., incomplete stent apposition.	9 Months
change in neointimal volume from post procedure to follow-up	9 Months
change in MLD within stent	9 Months
minimum lumen area (MLA) within stent	9 Months
lumen, plaque and vessel measurements at the stent edges (outside stent)	9 Months

Collaborators and Investigators

• Sponsor: Boston Scientific Corporation
• Investigators: Principal Investigator: Gregg W. Stone, MD, Columbia University; Principal Investigator: Stephen G. Ellis, MD, The Cleveland Clinic

Publications and helpful links

General Publications

• Wakabayashi K, Mintz GS, Weissman NJ, Stone GW, Ellis SG, Grube E, Ormiston JA, Turco MA, Pakala R, Xue Z, Desale S, Laynez-Carnicero A, Romaguera R, Sardi G, Pichard AD, Waksman R. Impact of drug-eluting stents on distal vessels. Circ Cardiovasc Interv. 2012 Apr;5(2):211-9. doi: 10.1161/CIRCINTERVENTIONS.111.965780. Epub 2012 Apr 10.
• Doi H, Maehara A, Mintz GS, Yu A, Wang H, Mandinov L, Popma JJ, Ellis SG, Grube E, Dawkins KD, Weissman NJ, Turco MA, Ormiston JA, Stone GW. Impact of post-intervention minimal stent area on 9-month follow-up patency of paclitaxel-eluting stents: an integrated intravascular ultrasound analysis from the TAXUS IV, V, and VI and TAXUS ATLAS Workhorse, Long Lesion, and Direct Stent Trials. JACC Cardiovasc Interv. 2009 Dec;2(12):1269-75. doi: 10.1016/j.jcin.2009.10.005.
• Stone GW, Ellis SG, Cannon L, Mann JT, Greenberg JD, Spriggs D, O'Shaughnessy CD, DeMaio S, Hall P, Popma JJ, Koglin J, Russell ME; TAXUS V Investigators. Comparison of a polymer-based paclitaxel-eluting stent with a bare metal stent in patients with complex coronary artery disease: a randomized controlled trial. JAMA. 2005 Sep 14;294(10):1215-23. doi: 10.1001/jama.294.10.1215.

Study record dates

Study Major Dates

• Study Start: February 1, 2003
• Primary Completion (Actual): December 1, 2004
• Study Completion (Actual): April 1, 2009

Study Registration Dates

• First Submitted: March 9, 2006
• First Submitted That Met QC Criteria: March 9, 2006
• First Posted (Estimate): March 13, 2006

Study Record Updates

• Last Update Posted (Estimate): August 6, 2010
• Last Update Submitted That Met QC Criteria: August 5, 2010
• Last Verified: August 1, 2010

More Information

Terms related to this study

• Keywords: stent; Stenosis; revascularization; Coronary; Artery; restenosis; Drug-eluting
• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Coronary Disease; Coronary Stenosis; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Paclitaxel
• Other Study ID Numbers: TAXUS V De novo; S5442