Clinical trial NCT00042081: Prevention of Autogenous Vein Graft Failure in Coronary Artery Bypass Procedures
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Coronary Artery Disease
Keywords: CABG
coronary artery bypass surgery
coronary artery disease
coronary arteriosclerosis
coronary stenosis
coronary occlusion
Lead sponsor: Anesiva, Inc.
Sponsor class: INDUSTRY
First posted: 2002-07-24
Enrollment: 3000
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Brookwood Medical Center
state: Alabama
city: Birmingham
country: United States
facility: Cardio-Thoracic Surgeons, P.C.
state: Alabama
city: Birmingham
country: United States
facility: Baptist Medical Center - Montclair
state: Alabama
city: Birmingham
country: United States
facility: Cardio-Thoracic Surgeons, P.C.
state: Alabama
city: Birmingham
country: United States
facility: Cardio-Thoracic Surgeons, P.C.
state: Alabama
city: Birmingham
country: United States
facility: Medical Center East
state: Alabama
city: Daly City
country: United States
facility: Seton Medical Center
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Palm Springs
country: United States
facility: Desert Regional Medical Center
state: California
city: Stockton
country: United States
facility: St. Joseph's Medical Center
state: California
city: Bridgeport
country: United States
facility: St. Vincent's Medical Center
state: Connecticut
city: Washington
country: United States
facility: Washington Hospital Center
state: District of Columbia
city: Atlantis
country: United States
facility: Florida Cardiovascular Research
state: Florida
city: Atlantis
country: United States
facility: JFK Medical Center
state: Florida
city: Clearwater
country: United States
facility: Morton Plant Hospital
state: Florida
city: Melbourne
country: United States
facility: Holmes Regional Medical Center
state: Florida
city: Orlando
country: United States
facility: Cardiovascular Surgeons, P.A.
state: Florida
city: Orlando
country: United States
facility: Florida Hospital
state: Florida
city: Orlando
country: United States
facility: Orlando Cardiovascular Center, LLLP
state: Florida
city: Orlando
country: United States
facility: Orlando Heart Center
state: Florida
city: Orlando
country: United States
facility: Orlando Regional Med Center
state: Florida
city: Orlando
country: United States
facility: Orlando Heart Center/Sand Lake
state: Florida
city: Sarasota
country: United States
facility: Clinical Research Center
state: Florida
city: Sarasota
country: United States
facility: Sarasota Memorial Health Care System
state: Florida
city: Atlanta
country: United States
facility: Crawford Long Hospital
state: Georgia
city: Atlanta
country: United States
facility: Emory University Hospital
state: Georgia
city: Belleville
country: United States
facility: St. Elizabeth's Hospital
state: Illinois
city: Belleville
country: United States
facility: Memorial Hospital
state: Illinois
city: Chicago
country: United States
facility: Northwestern Medical Facility Foundation
state: Illinois
city: Chicago
country: United States
facility: Northwestern Memorial Hospital
state: Illinois
city: Chicago
country: United States
facility: Rush Presbyterian St. Luke's Medical Center
state: Illinois
city: Chicago
country: United States
facility: Rush Professional Building
state: Illinois
city: Chicago
country: United States
facility: Resurrection Medical Center
state: Illinois
city: Evanston
country: United States
facility: Evanston Northwestern Healthcare, Highland Park Hospital
state: Illinois
city: Evanston
country: United States
facility: Evanston Northwestern Healthcare
state: Illinois
city: Evanston
country: United States
facility: St. Francis Hospital of Evanston
state: Illinois
city: Maywood
country: United States
facility: Loyola University Chicago Medical Center
state: Illinois
city: Naperville
country: United States
facility: Edward Hospital & Health Services
state: Illinois
city: Oak Lawn
country: United States
facility: Advocate Christ Hospital and Medical Center
state: Illinois
city: Peoria
country: United States
facility: OSF St. Francis Medical Center
state: Illinois
city: Springfield
country: United States
facility: Memorial Medical Center
state: Illinois
city: Springfield
country: United States
facility: Southern Illinois University School of Medicine, Dep. of Surgery, Div. of Cardiothoracic Surgery
state: Illinois
city: Springfield
country: United States
facility: Southern Illinois University School of Medicine, Department of Surgery, Division of Cardiothoracic Surgery
state: Illinois
city: Springfield
country: United States
facility: St. John's Hospital
state: Illinois
city: Winfield
country: United States
facility: Central DuPage Hospital
state: Illinois
city: Indianapolis
country: United States
facility: St. Vincent Hospital and Health Care Service
state: Indiana
city: Indianapolis
country: United States
facility: The Heart Center of Indiana
state: Indiana
city: Davenport
country: United States
facility: Genesis Heart Institute
state: Iowa
city: Davenport
country: United States
facility: Genesis Medical Center
state: Iowa
city: Des Moines
country: United States
facility: Iowa Methodist Medical Center
state: Iowa
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: Overland Park
country: United States
facility: Georgetown Professional Plaza
state: Kansas
city: Shawnee Mission
country: United States
facility: Shawnee Mission Medical Center
state: Kansas
city: Louisville
country: United States
facility: Jewish Hospital Health Care Services
state: Kentucky
city: Portland
country: United States
facility: Maine Medical Center
state: Maine
city: Baltimore
country: United States
facility: University of Maryland Medical Center
state: Maryland
city: Baltimore
country: United States
facility: Cardiac Surgery Associates
state: Maryland
city: Baltimore
country: United States
facility: Sinai Hospital of Baltimore
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins Hospital
state: Maryland
city: Salisbury
country: United States
facility: Peninsula Regional Medical Center
state: Maryland
city: Takoma Park
country: United States
facility: Washington Adventist Hospital
state: Maryland
city: Towson
country: United States
facility: Cardiac Surgery Associates
state: Maryland
city: Towson
country: United States
facility: Midatlantic Cardiovascular Associates, P.A.
state: Maryland
city: Towson
country: United States
facility: St. Joseph Medical Center
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Brigham & Women's Hospital
state: Massachusetts
city: Springfield
country: United States
facility: Baystate Medical Center
state: Massachusetts
city: Flint
country: United States
facility: McLaren Regional Medical Center
state: Michigan
city: Grand Rapids
country: United States
facility: Spectrum Health Hospitals
state: Michigan
city: Lansing
country: United States
facility: Ingham Regional Medical Center
state: Michigan
city: Lansing
country: United States
facility: Thoracic & Cardiovascular Healthcare Foundation
state: Michigan
city: Lansing
country: United States
facility: Thoracic & Cardiovascular Institute
state: Michigan
city: Petoskey
country: United States
facility: Cardiology Consultants, PC
state: Michigan
city: Petoskey
country: United States
facility: Great Lakes Cardiothoracic and Vascular Surgery
state: Michigan
city: Petoskey
country: United States
facility: Northern Michigan Hospital
state: Michigan
city: Petoskey
country: United States
facility: Petoskey Cardiology
state: Michigan
city: Saginaw
country: United States
facility: Michigan Cardiovascular Institute
state: Michigan
city: Saginaw
country: United States
facility: Convenant Medical Center
state: Michigan
city: Duluth
country: United States
facility: St. Mary's/Duluth Clinic Health System
state: Minnesota
city: Minneapolis
country: United States
facility: Abbott Northwestern Hospital
state: Minnesota
city: Minneapolis
country: United States
facility: Park Nicollet Institute
state: Minnesota
city: St. Louis Park
country: United States
facility: Methodist Hospital
state: Minnesota
city: St. Louis Park
country: United States
facility: Park Nicollet Heart Center
state: Minnesota
city: Hattiesburg
country: United States
facility: Forrest General Hospital
state: Mississippi
city: Joplin
country: United States
facility: St. John's Regional Medical Center
state: Missouri
city: Kansas City
country: United States
facility: 930 Carondelet Drive
state: Missouri
city: St. Louis
country: United States
facility: Missouri Baptist Medical Center
state: Missouri
city: Omaha
country: United States
facility: Nebraska Methodist Hospital
state: Nebraska
city: Omaha
country: United States
facility: Nebraska Heart Institute
state: Nebraska
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Papillion
country: United States
facility: Nebraska Heart Institute
state: Nebraska
city: Morristown
country: United States
facility: Morristown Memorial Hospital
state: New Jersey
city: New Brunswick
country: United States
facility: Robert Wood Johnson University Hospital
state: New Jersey
city: New Brunswick
country: United States
facility: Umdnj-Rwjms
state: New Jersey
city: Ridgewood
country: United States
facility: The Valley Hospital
state: New Jersey
city: New York
country: United States
facility: Lenox Hill Hospital
state: New York
city: New York
country: United States
facility: New York Presbyterian Medical Center, Milstein Hospital Building
state: New York
city: Valhalla
country: United States
facility: Westchester Medical Center
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina Hospitals
state: North Carolina
city: Chapel Hill
country: United States
facility: Ambulatory Care Center
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Gastonia
country: United States
facility: Gaston Memorial Hospital
state: North Carolina
city: Greenville
country: United States
facility: Pitt County Memorial Hospital
state: North Carolina
city: Greenville
country: United States
facility: Brody School of Medicine, East Carolina University
state: North Carolina
city: Pinehurst
country: United States
facility: FirstHealth Moore Regional Hospital
state: North Carolina
city: Winston Salem
country: United States
facility: Walley, Morgan & Duncan, M.D., P.A.
state: North Carolina
city: Winston-Salem
country: United States
facility: Forysyth Medical Center
state: North Carolina
city: Fargo
country: United States
facility: MeritCare Clinic at MeritCare Hospital
state: North Dakota
city: Fargo
country: United States
facility: MeritCare Medical Group
state: North Dakota
city: Akron
country: United States
facility: Akron General Medical Center
state: Ohio
city: Canton
country: United States
facility: Aultman Health Foundation
state: Ohio
city: Cincinnati
country: United States
facility: Cardiovascular & Thoracic Surgeons
state: Ohio
city: Cincinnati
country: United States
facility: Good Samaritan Hospital
state: Ohio
city: Cincinnati
country: United States
facility: Bethesda North Hospital
state: Ohio
city: Cincinnati
country: United States
facility: Cardiovascular & Thoracic Surgeons, Inc.
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University Medical Center
state: Ohio
city: Columbus
country: United States
facility: Riverside Methodist Hospital
state: Ohio
city: Kettering
country: United States
facility: Kettering Medical Center Network, Kettering Hospital
state: Ohio
city: Toledo
country: United States
facility: St. Vincent Mercy Medical Center
state: Ohio
city: Bethlehem
country: United States
facility: St. Luke's Hospital
state: Pennsylvania
city: Hershey
country: United States
facility: Penn State Milton S. Hershey Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Presbyterian Hospital, University of Pennsylvania Health System
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Allegheny General Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center, Presbyterian Hospital
state: Pennsylvania
city: Sayre
country: United States
facility: Guthrie Clinic
state: Pennsylvania
city: Sayre
country: United States
facility: Robert Packer Hospital
state: Pennsylvania
city: West Chester
country: United States
facility: The Chester County Hospital
state: Pennsylvania
city: Wynnewood
country: United States
facility: Lankenau Hospital
state: Pennsylvania
city: Greenville
country: United States
facility: Greenville Hospital System
state: South Carolina
city: Greenville
country: United States
facility: Upstate Cardiothoracic Surgery, Greenville Hospital System
state: South Carolina
city: Memphis
country: United States
facility: Saint Francis Hospital
state: Tennessee
city: Austin
country: United States
facility: Heart Hospital of Austin
state: Texas
city: Dallas
country: United States
facility: Medical City Dallas Hospital
state: Texas
city: Dallas
country: United States
facility: Presbyterian Hospital of Dallas
state: Texas
city: Dallas
country: United States
facility: St. Paul University Hospital
state: Texas
city: Denton
country: United States
facility: Denton Regional Medical Center
state: Texas
city: Plano
country: United States
facility: Medical Center Plano
state: Texas
city: San Antonio
country: United States
facility: Southwest Texas Methodist Hospital
state: Texas
city: San Antonio
country: United States
facility: Northeast Methodist Hospital
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah Health Sciences Center
state: Utah
city: Lynchburg
country: United States
facility: Lynchburg General Hospital
state: Virginia
city: Norfolk
country: United States
facility: Sentara Norfolk General Hospital
state: Virginia
city: Norfolk
country: United States
facility: Mid-Atlantic Cardiothoracic Surgeons, Ltd.
state: Virginia
city: Bellingham
country: United States
facility: St. Joseph Hospital
state: Washington
city: Spokane
country: United States
facility: Deaconess Medical Center
state: Washington
city: Spokane
country: United States
facility: Northwest Heart and Lung Surgical Associates
state: Washington
city: Charleston
country: United States
facility: CAMC Health Education and Research Institute, Clinical Trials Center
state: West Virginia
city: Charleston
country: United States
facility: Charleston Area Medical Center
state: West Virginia
city: Appleton
country: United States
facility: Appleton Heart Institute at Appleton Medical Center
state: Wisconsin
city: Milwaukee
country: United States
facility: St. Luke's Medical Center
state: Wisconsin
city: Waukesha
country: United States
facility: Waukesha Memorial Hospital
state: Wisconsin
city: Wausau
country: United States
facility: Community Health Care/Wausau Hospital
state: Wisconsin
city: Wausau
country: United States
facility: Wausau Heart and Lung Surgeons
state: Wisconsin
Study officials:
affiliation: Anesiva, Inc.
name: Todd Lorenz, M.D.
role: STUDY_DIRECTOR
References:
citation: 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 prevention of vein graft failure following coronary artery bypass graft surgery: PREVENT IV: a randomized controlled trial. JAMA. 2005 Nov 16;294(19):2446-54. doi: 10.1001/jama.294.19.2446.
citation: Harskamp RE, Alexander JH, Ferguson TB Jr, Hager R, Mack MJ, Englum B, Wojdyla D, Schulte PJ, Kouchoukos NT, de Winter RJ, Gibson CM, Peterson ED, Harrington RA, Smith PK, Lopes RD. Frequency and Predictors of Internal Mammary Artery Graft Failure and Subsequent Clinical Outcomes: Insights From the Project of Ex-vivo Vein Graft Engineering via Transfection (PREVENT) IV Trial. Circulation. 2016 Jan 12;133(2):131-8. doi: 10.1161/CIRCULATIONAHA.115.015549. Epub 2015 Dec 8.
citation: Hess CN, Lopes RD, Gibson CM, Hager R, Wojdyla DM, Englum BR, Mack MJ, Califf RM, Kouchoukos NT, Peterson ED, Alexander JH. Saphenous vein graft failure after coronary artery bypass surgery: insights from PREVENT IV. Circulation. 2014 Oct 21;130(17):1445-51. doi: 10.1161/CIRCULATIONAHA.113.008193. Epub 2014 Sep 26.
citation: Harskamp RE, Alexander JH, Schulte PJ, Brophy CM, Mack MJ, Peterson ED, Williams JB, Gibson CM, Califf RM, Kouchoukos NT, Harrington RA, Ferguson TB Jr, Lopes RD. Vein graft preservation solutions, patency, and outcomes after coronary artery bypass graft surgery: follow-up from the PREVENT IV randomized clinical trial. JAMA Surg. 2014 Aug;149(8):798-805. doi: 10.1001/jamasurg.2014.87.
citation: Lopes RD, Williams JB, Mehta RH, Reyes EM, Hafley GE, Allen KB, Mack MJ, Peterson ED, Harrington RA, Gibson CM, Califf RM, Kouchoukos NT, Ferguson TB, Lorenz TJ, Alexander JH. Edifoligide and long-term outcomes after coronary artery bypass grafting: PRoject of Ex-vivo Vein graft ENgineering via Transfection IV (PREVENT IV) 5-year results. Am Heart J. 2012 Sep;164(3):379-386.e1. doi: 10.1016/j.ahj.2012.05.019.