Randomized Trial Evaluating Slow-Release Formulation TAXUS Paclitaxel-Eluting Coronary Stent in the Treatment of In-Stent Restenosis (TAXUS V ISR)

A Prospective, Randomized Trial Evaluating Slow-Release Formulation TAXUS Paclitaxel-Eluting Coronary Stent in the Treatment of In-Stent Restenosis

The objective of this study is to evaluate the safety and effectiveness of the TAXUS Express2 Paclitaxel-Eluting Coronary Stent System as compared to brachytherapy in patients experiencing in-stent restenosis.

Study Overview

• Status: Completed
• Conditions: Coronary Restenosis
• Intervention / Treatment: Device: TAXUS Express2; Procedure: Brachytherapy (beta source)

Detailed Description

Percutaneous approaches to in-stent restenosis (ISR) have included balloon angioplasty alone, rotational atherectomy, cutting balloon angioplasty, directional coronary atherectomy, excimer laser angioplasty, placement of a second stent or any combination thereof, and intra-coronary brachytherapy. Of these, only brachytherapy has been shown to reduce recurrent restenosis after PCI for ISR, - and is now considered the standard of care. Logistical considerations in establishing and maintaining a radiation program have limited the widespread availability of this modality. These considerations include the need for involvement of radiation oncologists, physicists, and safety officers; nuclear licensing requirements; need for increased shielding and safety training; equipment and procedural complexities; as well as increased procedural time and costs. Furthermore, recurrent ISR after brachytherapy may still occur. Stent based drug delivery for the treatment of ISR holds promise as a much simpler, safer and potentially more effective alternative to brachytherapy.

This is a prospective, randomized (1:1), open-label, multicenter, safety and efficacy trial for the treatment of in-stent restenosis. The primary objective is to demonstrate a superior or non-inferior 9-month target vessel revascularization (TVR) rate for TAXUS-SR stent compared to intra-coronary brachytherapy (beta source).

• Study Type: Interventional
• Enrollment (Actual): 488
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2C4
      • Toronto General Hospital
    • Toronto, Ontario, Canada, M4N 3M5
      • Sunnybrook & Women's College Health Sciences Centre
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35211
      • Baptist Medical Center Princeton
  • California
    • LaJolla, California, United States, 92037
      • Scripps Green Hospital
    • 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
    • Orlando, Florida, United States, 32803
      • Florida Hospital
  • Georgia
    • Atlanta, Georgia, United States, 30309
      • Piedmont 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, 20912-6367
      • Washington Adventist Hospital
  • Massachusetts
    • 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
    • Grand Rapids, Michigan, United States, 49503
      • Spectrum Health Hospitals
    • Petoskey, Michigan, United States, 49770
      • Cardiac & Vascular Research Center of Northern Michigan
  • Minnesota
    • Minneapolis, Minnesota, United States, 55407-1195
      • Abbott Northwestern 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 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
      • Lenox Hill Hospital
    • New York, New York, United States, 10021
      • Columbia University Medical Center
  • 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
    • 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
    • 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, 02906
      • The Miriam 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
    • Houston, Texas, United States, 77030
      • The Methodist Hospital Research Institute in Cardiovascular Interventions
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia
  • Washington
    • Seattle, Washington, United States, 98104
      • Swedish 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:

• Cumulative target lesion length is </= 46 mm (visual estimate).
• Reference vessel diameter (RVD) is >/= 2.5 and </= 3.75 mm (visual estimate)
• Left ventricular ejection fraction (LVEF) is >/= 25%

Exclusion Criteria:

• Any previous or planned treatment with a non-study anti-restenotic drug-coated or drug-eluting coronary stent in the target vessel. (Note:previous or planned treatment with heparin or phosphorylcholine coated stents is acceptable, as long as, the procedure with the non-study stent meets the protocol defined criteria for non-target lesion interventions.)
• Previous or planned treatment with intra-coronary brachytherapy (gamma or beta source) in the target vessel
• Previous external radiotherapy to the heart or target vessel area
• Known genetic radiation sensitivity disorders (i.e. ataxia-telangiectasia, etc.)
• Side branch of the target lesion includes ostial narrowing >/= 50% diameter stenosis (DS) and is >/= 2.0 mm diameter
• Target lesion has been previously treated for ISR with the placement of a second stent(s), which covers >/= 50% of the original stent length (a true "stent sandwich")
• Target vessel is pre-treated with an unapproved device, directional or rotational coronary atherectomy, laser, or transluminal extraction catheter immediately prior to delivery of randomized treatment (stent placement or intra-coronary brachytherapy)
• Recent myocardial infarction (MI) (symptom onset </= 72 hours prior to randomization)
• CK-MB >2x the local laboratory's upper limit of normal (ULN) (refers to a measured value on the day of the index procedure as drawn per protocol)
• Anticipated treatment with warfarin during any period in the 6 months post index procedure
• Anticipated treatment with paclitaxel, oral rapamycin or colchicine during any period in the 9 months post index procedure
• Planned use of both the study stent and a non-study stent (i.e., commercial stent) in the treatment of the target lesion

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm 2	Procedure: Brachytherapy (beta source); Brachytherapy (beta source)
Experimental: Arm 1	Device: TAXUS Express2; Paclitaxel-Eluting Coronary Stent System

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Rate of Target Vessel Revascularization	9 Months

Secondary Outcome Measures

Outcome Measure	Time Frame
Stent thrombosis rate	5 Years
Incidence of composite major adverse cardiac events (MACE) and the individual components of MACE	assessed at discharge, 1, 4 and 9 months post index procedure and annually for 5 years
Target Vessel Failure (TVF, defined as any ischemia-driven revascularization of the target vessel, MI related to the target vessel, or death related to the target vessel).	5 Years
Clinical procedural success and technical success	5 Years
Binary restenosis rate	5 years
Evaluate outcomes and treatment of recurrent restenosis in the TAXUS stent arm	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
Identification of potential safety issues.	9 Months
Change in neointimal volume from post procedure to follow-up	9 Months
Change in MLD within the stent or area of brachytherapy	9 Months
Minimum lumen area (MLA) within the stent or area of brachytherapy	9 Months
Lumen, plaque and vessel measurements at the treatment edges (outside of the stent or area of brachytherapy)	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

• Stone GW, Ellis SG, O'Shaughnessy CD, Martin SL, Satler L, McGarry T, Turco MA, Kereiakes DJ, Kelley L, Popma JJ, Russell ME; TAXUS V ISR Investigators. Paclitaxel-eluting stents vs vascular brachytherapy for in-stent restenosis within bare-metal stents: the TAXUS V ISR randomized trial. JAMA. 2006 Mar 15;295(11):1253-63. doi: 10.1001/jama.295.11.1253. Epub 2006 Mar 12.

Study record dates

Study Major Dates

• Study Start: June 1, 2003
• Primary Completion (Actual): December 1, 2004
• Study Completion (Actual): January 1, 2010

Study Registration Dates

• First Submitted: February 3, 2006
• First Submitted That Met QC Criteria: February 3, 2006
• First Posted (Estimate): February 7, 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

• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Coronary Disease; Coronary Stenosis; Coronary Restenosis
• Other Study ID Numbers: S5442; TAXUS V ISR