Prevention of Autogenous Vein Graft Failure in Coronary Artery Bypass Procedures

Coronary Artery Disease Clinical Trial

Official title:

A Phase III, Multi-Center Randomized, Double-Blind, Placebo-Controlled Trial of the Ex Vivo Treatment With CGT003 of Coronary Vein Grafts in Patients Undergoing Coronary Artery Bypass Graft Procedures

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00042081
• Other study ID #: CGT003-04
• Status: Completed
• Phase: Phase 3
• First received: July 22, 2002
• Last updated: May 4, 2006
• Start date: July 2002
• Est. completion date: February 2005

Study information

• Verified date: July 2005
• Source: Anesiva, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine the efficacy of graft pretreatment with CGT003 (E2F Duplex Decoy), as compared to placebo, on the incidence of patients experiencing vein graft failure after coronary artery bypass surgery.

Description:

Coronary vascular disease manifested by narrowing of the coronary arteries is one of the more common manifestations of atherosclerotic vascular disease. The clinical manifestations of coronary artery disease include death, angina pectoris, myocardial infarction, congestive heart failure and arrhythmia. Restoration of circulation to the heart may be undertaken using a variety of techniques including angioplasty, stenting, and bypass grafting.

Approximately 359,000 patients underwent coronary bypass procedures in the U.S. in 1999. Long term studies have observed an incidence of vein graft occlusion at 19% at 1 year, 25% at 5 years and 50% by 15 years after operation for an overall rate of 2.5% per year after the first year of observation. The consequences of graft failure are as significant as those of primary atherosclerotic disease and include ischemia, myocardial infarction and death.

CGT003 is a novel therapeutic that is under investigation as a treatment to prevent vein graft failure. It acts by inhibiting the transcription factor, E2F, which is activated in response to injury such as that which occurs when thin-walled vein grafts are exposed to the pressures of the arterial circulation. Blockade of E2F inhibits smooth muscle cell proliferation and redirects the vein graft remodeling that occurs within the first several days after implantation towards medial hypertrophy and strengthening of the medial layer and blunts formation of neointima. Inhibition of neotinimal formation coupled with expansion of the media should result in a decreased risk of the accelerated atherosclerosis and consequent vein graft failure over several years.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 3000
• Est. completion date: February 2005
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

PATIENTS MUST:

• Have coronary artery disease and be scheduled to undergo a coronary artery bypass (CABG) procedure that is to include at least two segments of autogenous vein (sequential grafts do not count as two separate grafts).

• Be between 18 and 80 years old.

• Have a documented negative serum pregnancy test for all women of childbearing potential.

• Be using an acceptable method of birth control if of reproductive potential.

• Have agreed to participate voluntarily and signed and dated an IRB-approved, Patient Informed Consent form.

• (If one of the first 2400 patients enrolled) have agreed to participate voluntarily and signed and dated an IRB-approved, Patient Informed Consent form for the Angiography population.

• Note: Patients who are to receive an arterial bypass to the left anterior descending artery in addition to the two vein grafts required by the protocol ARE eligible for this study.

• Note: Patients ARE eligible for enrollment regardless of whether the planned procedure is to be on or off cardiopulmonary bypass pump.

• Note: Patients who do not wish to undergo elective Angiography at one year SHOULD NOT be enrolled in the first 2400 patients.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Double-Blind, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Coronary Artery Disease
• Coronary Disease
• Myocardial Ischemia

Intervention

Drug:
• CGT003 (E2F Duplex Decoy)

Locations

Country	Name	City	State
United States	Akron General Medical Center	Akron	Ohio
United States	Appleton Heart Institute at Appleton Medical Center	Appleton	Wisconsin
United States	Crawford Long Hospital	Atlanta	Georgia
United States	Emory University Hospital	Atlanta	Georgia
United States	Florida Cardiovascular Research	Atlantis	Florida
United States	JFK Medical Center	Atlantis	Florida
United States	Heart Hospital of Austin	Austin	Texas
United States	Cardiac Surgery Associates	Baltimore	Maryland
United States	Johns Hopkins Hospital	Baltimore	Maryland
United States	Sinai Hospital of Baltimore	Baltimore	Maryland
United States	University of Maryland Medical Center	Baltimore	Maryland
United States	Memorial Hospital	Belleville	Illinois
United States	St. Elizabeth's Hospital	Belleville	Illinois
United States	St. Joseph Hospital	Bellingham	Washington
United States	St. Luke's Hospital	Bethlehem	Pennsylvania
United States	Baptist Medical Center - Montclair	Birmingham	Alabama
United States	Brookwood Medical Center	Birmingham	Alabama
United States	Cardio-Thoracic Surgeons, P.C.	Birmingham	Alabama
United States	Cardio-Thoracic Surgeons, P.C.	Birmingham	Alabama
United States	Cardio-Thoracic Surgeons, P.C.	Birmingham	Alabama
United States	Medical Center East	Birmingham	Alabama
United States	Brigham & Women's Hospital	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	St. Vincent's Medical Center	Bridgeport	Connecticut
United States	Aultman Health Foundation	Canton	Ohio
United States	Ambulatory Care Center	Chapel Hill	North Carolina
United States	University of North Carolina Hospitals	Chapel Hill	North Carolina
United States	CAMC Health Education and Research Institute, Clinical Trials Center	Charleston	West Virginia
United States	Charleston Area Medical Center	Charleston	West Virginia
United States	Northwestern Medical Facility Foundation	Chicago	Illinois
United States	Northwestern Memorial Hospital	Chicago	Illinois
United States	Resurrection Medical Center	Chicago	Illinois
United States	Rush Presbyterian St. Luke's Medical Center	Chicago	Illinois
United States	Rush Professional Building	Chicago	Illinois
United States	Bethesda North Hospital	Cincinnati	Ohio
United States	Cardiovascular & Thoracic Surgeons	Cincinnati	Ohio
United States	Cardiovascular & Thoracic Surgeons, Inc.	Cincinnati	Ohio
United States	Good Samaritan Hospital	Cincinnati	Ohio
United States	Morton Plant Hospital	Clearwater	Florida
United States	Riverside Methodist Hospital	Columbus	Ohio
United States	The Ohio State University Medical Center	Columbus	Ohio
United States	Medical City Dallas Hospital	Dallas	Texas
United States	Presbyterian Hospital of Dallas	Dallas	Texas
United States	St. Paul University Hospital	Dallas	Texas
United States	Seton Medical Center	Daly City	California
United States	Genesis Heart Institute	Davenport	Iowa
United States	Genesis Medical Center	Davenport	Iowa
United States	Denton Regional Medical Center	Denton	Texas
United States	Iowa Methodist Medical Center	Des Moines	Iowa
United States	St. Mary's/Duluth Clinic Health System	Duluth	Minnesota
United States	Duke University Medical Center	Durham	North Carolina
United States	Evanston Northwestern Healthcare	Evanston	Illinois
United States	Evanston Northwestern Healthcare, Highland Park Hospital	Evanston	Illinois
United States	St. Francis Hospital of Evanston	Evanston	Illinois
United States	MeritCare Clinic at MeritCare Hospital	Fargo	North Dakota
United States	MeritCare Medical Group	Fargo	North Dakota
United States	McLaren Regional Medical Center	Flint	Michigan
United States	Gaston Memorial Hospital	Gastonia	North Carolina
United States	Spectrum Health Hospitals	Grand Rapids	Michigan
United States	Brody School of Medicine, East Carolina University	Greenville	North Carolina
United States	Greenville Hospital System	Greenville	South Carolina
United States	Pitt County Memorial Hospital	Greenville	North Carolina
United States	Upstate Cardiothoracic Surgery, Greenville Hospital System	Greenville	South Carolina
United States	Forrest General Hospital	Hattiesburg	Mississippi
United States	Penn State Milton S. Hershey Medical Center	Hershey	Pennsylvania
United States	St. Vincent Hospital and Health Care Service	Indianapolis	Indiana
United States	The Heart Center of Indiana	Indianapolis	Indiana
United States	University of Iowa Hospitals and Clinics	Iowa City	Iowa
United States	St. John's Regional Medical Center	Joplin	Missouri
United States	930 Carondelet Drive	Kansas City	Missouri
United States	Kettering Medical Center Network, Kettering Hospital	Kettering	Ohio
United States	Ingham Regional Medical Center	Lansing	Michigan
United States	Thoracic & Cardiovascular Healthcare Foundation	Lansing	Michigan
United States	Thoracic & Cardiovascular Institute	Lansing	Michigan
United States	Cedars-Sinai Medical Center	Los Angeles	California
United States	Jewish Hospital Health Care Services	Louisville	Kentucky
United States	Lynchburg General Hospital	Lynchburg	Virginia
United States	Loyola University Chicago Medical Center	Maywood	Illinois
United States	Holmes Regional Medical Center	Melbourne	Florida
United States	Saint Francis Hospital	Memphis	Tennessee
United States	St. Luke's Medical Center	Milwaukee	Wisconsin
United States	Abbott Northwestern Hospital	Minneapolis	Minnesota
United States	Park Nicollet Institute	Minneapolis	Minnesota
United States	Morristown Memorial Hospital	Morristown	New Jersey
United States	Edward Hospital & Health Services	Naperville	Illinois
United States	Robert Wood Johnson University Hospital	New Brunswick	New Jersey
United States	Umdnj-Rwjms	New Brunswick	New Jersey
United States	Lenox Hill Hospital	New York	New York
United States	New York Presbyterian Medical Center, Milstein Hospital Building	New York	New York
United States	Mid-Atlantic Cardiothoracic Surgeons, Ltd.	Norfolk	Virginia
United States	Sentara Norfolk General Hospital	Norfolk	Virginia
United States	Advocate Christ Hospital and Medical Center	Oak Lawn	Illinois
United States	Nebraska Heart Institute	Omaha	Nebraska
United States	Nebraska Methodist Hospital	Omaha	Nebraska
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Cardiovascular Surgeons, P.A.	Orlando	Florida
United States	Florida Hospital	Orlando	Florida
United States	Orlando Cardiovascular Center, LLLP	Orlando	Florida
United States	Orlando Heart Center	Orlando	Florida
United States	Orlando Heart Center/Sand Lake	Orlando	Florida
United States	Orlando Regional Med Center	Orlando	Florida
United States	Georgetown Professional Plaza	Overland Park	Kansas
United States	Desert Regional Medical Center	Palm Springs	California
United States	Nebraska Heart Institute	Papillion	Nebraska
United States	OSF St. Francis Medical Center	Peoria	Illinois
United States	Cardiology Consultants, PC	Petoskey	Michigan
United States	Great Lakes Cardiothoracic and Vascular Surgery	Petoskey	Michigan
United States	Northern Michigan Hospital	Petoskey	Michigan
United States	Petoskey Cardiology	Petoskey	Michigan
United States	Hospital of the University of Pennsylvania	Philadelphia	Pennsylvania
United States	Presbyterian Hospital, University of Pennsylvania Health System	Philadelphia	Pennsylvania
United States	FirstHealth Moore Regional Hospital	Pinehurst	North Carolina
United States	Allegheny General Hospital	Pittsburgh	Pennsylvania
United States	University of Pittsburgh Medical Center, Presbyterian Hospital	Pittsburgh	Pennsylvania
United States	Medical Center Plano	Plano	Texas
United States	Maine Medical Center	Portland	Maine
United States	The Valley Hospital	Ridgewood	New Jersey
United States	Convenant Medical Center	Saginaw	Michigan
United States	Michigan Cardiovascular Institute	Saginaw	Michigan
United States	Peninsula Regional Medical Center	Salisbury	Maryland
United States	University of Utah Health Sciences Center	Salt Lake City	Utah
United States	Northeast Methodist Hospital	San Antonio	Texas
United States	Southwest Texas Methodist Hospital	San Antonio	Texas
United States	Clinical Research Center	Sarasota	Florida
United States	Sarasota Memorial Health Care System	Sarasota	Florida
United States	Guthrie Clinic	Sayre	Pennsylvania
United States	Robert Packer Hospital	Sayre	Pennsylvania
United States	Shawnee Mission Medical Center	Shawnee Mission	Kansas
United States	Deaconess Medical Center	Spokane	Washington
United States	Northwest Heart and Lung Surgical Associates	Spokane	Washington
United States	Baystate Medical Center	Springfield	Massachusetts
United States	Memorial Medical Center	Springfield	Illinois
United States	Southern Illinois University School of Medicine, Dep. of Surgery, Div. of Cardiothoracic Surgery	Springfield	Illinois
United States	Southern Illinois University School of Medicine, Department of Surgery, Division of Cardiothoracic Surgery	Springfield	Illinois
United States	St. John's Hospital	Springfield	Illinois
United States	Missouri Baptist Medical Center	St. Louis	Missouri
United States	Methodist Hospital	St. Louis Park	Minnesota
United States	Park Nicollet Heart Center	St. Louis Park	Minnesota
United States	St. Joseph's Medical Center	Stockton	California
United States	Washington Adventist Hospital	Takoma Park	Maryland
United States	St. Vincent Mercy Medical Center	Toledo	Ohio
United States	Cardiac Surgery Associates	Towson	Maryland
United States	Midatlantic Cardiovascular Associates, P.A.	Towson	Maryland
United States	St. Joseph Medical Center	Towson	Maryland
United States	Westchester Medical Center	Valhalla	New York
United States	Washington Hospital Center	Washington	District of Columbia
United States	Waukesha Memorial Hospital	Waukesha	Wisconsin
United States	Community Health Care/Wausau Hospital	Wausau	Wisconsin
United States	Wausau Heart and Lung Surgeons	Wausau	Wisconsin
United States	The Chester County Hospital	West Chester	Pennsylvania
United States	Central DuPage Hospital	Winfield	Illinois
United States	Walley, Morgan & Duncan, M.D., P.A.	Winston Salem	North Carolina
United States	Forysyth Medical Center	Winston-Salem	North Carolina
United States	Lankenau Hospital	Wynnewood	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Anesiva, Inc.

Country where clinical trial is conducted

United States, 

References & Publications (1)

Alexander JH, Hafley G, Harrington RA, Peterson ED, Ferguson TB Jr, Lorenz TJ, Goyal A, Gibson M, Mack MJ, Gennevois D, Califf RM, Kouchoukos NT; PREVENT IV Investigators. Efficacy and safety of edifoligide, an E2F transcription factor decoy, for preventi — View Citation