Prevention of Autogenous Vein Graft Failure in Coronary Artery Bypass Procedures

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Coronary Artery Disease

Intervention / Treatment
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* Drug: CGT003 (E2F Duplex Decoy)


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Double


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: CGT003 (E2F Duplex Decoy)|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CABG, coronary artery bypass surgery, coronary artery disease, coronary arteriosclerosis, coronary stenosis, coronary occlusion