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This is a randomized-controlled clinical trial that will randomize 120 patients undergoing clinically-indicated coronary artery bypass graft surgery to prasugrel at a dose of 10 mg daily or matching placebo for 12 months, starting at the time of hospital dismissal from surgery. The primary goal of the study is to determine whether prasugrel administration will prevent thrombus (clot) formation within a saphenous vein graft at 12 months, as examined by optical coherence tomography.
Aortocoronary saphenous vein graft failure is common and is associated with high morbidity and mortality. Thrombus formation plays a critical role in early saphenous vein graft occlusion and may predispose to subsequent atherosclerosis formation. Optical coherence tomography is a novel, high-resolution, intravascular imaging technique that can reliably identify thrombus. Based on the findings of earlier VA Cooperative Studies, aspirin significantly reduces the incidence of early saphenous vein graft failure and is currently used in nearly all patients undergoing coronary bypass graft surgery. Administration of clopidogrel for improving early saphenous vein graft patency has provided conflicting results in small randomized studies. Prasugrel is a novel thienopyridine that provides more rapid, consistent, and intense platelet inhibition than clopidogrel. However, in patients who undergo coronary artery bypass graft surgery, it remains unknown whether prasugrel may decrease thrombus formation in saphenous vein grafts during the first postoperative year, and whether this will result in less saphenous vein graft wall thickening, less lipid deposition in the saphenous vein graft wall and fewer clinical events without increasing the risk for severe bleeding.
Hypothesis: The investigators hypothesize that in patients undergoing clinically-indicated coronary artery bypass graft surgery, administration of prasugrel starting at dismissal from the index coronary bypass graft surgery hospitalization will result in lower prevalence of thrombus formation in a target SVG, as assessed by optical coherence tomography performed 12 months post surgery compared to placebo, with similar incidence of major bleeding.
This is a phase III, single-center, double-blind trial that will randomize 120 patients undergoing clinically-indicated coronary artery bypass graft surgery to prasugrel at a dose of 10 mg daily or matching placebo for 12 months, starting at the time of hospital dismissal from surgery. All patients will receive aspirin. Coronary angiography, optical coherence tomography, intravascular ultrasonography, and near-infrared spectroscopy of one target saphenous vein graft will be performed at 12 months to determine whether compared to placebo, administration of prasugrel will result in:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm 1: Prasugrel | Experimental | prasugrel 10 mg by mouth daily |
|
| Arm 2: Placebo | Placebo Comparator | placebo by mouth once daily |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Prasugrel | Drug | one 10 mg tablet by mouth daily |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| Prevalence of Intragraft Thrombus at 12-month Follow-up Optical Coherence Tomography Imaging | Number of patients with intragraft thrombus seen at 12 month follow-up by optical coherence tomography in imaged saphenous vein graft | 12 months |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Patients With Severe Bleeding Using the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO) Criteria | Number of patients with major bleeding defined by the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries criteria. | 12 months |
| Number of Patients With Angiographic Saphenous Vein Graft Failure |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Shuaib M. Abdullah, MD | VA North Texas Health Care System Dallas VA Medical Center, Dallas, TX | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| San Francisco VA Medical Center, San Francisco, CA | San Francisco | California | 94121 | United States | ||
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| ID | Title | Description |
|---|---|---|
| FG000 | Arm 1: Prasugrel | prasugrel 10 mg by mouth daily Prasugrel: one 10 mg tablet by mouth daily |
| FG001 | Arm 2: Placebo | placebo by mouth once daily Placebo: placebo similar in appearance to prasugrel |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Arm 1: Prasugrel | prasugrel 10 mg by mouth daily Prasugrel: one 10 mg tablet by mouth daily |
| BG001 | Arm 2: Placebo | placebo by mouth once daily Placebo: placebo similar in appearance to prasugrel |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Prevalence of Intragraft Thrombus at 12-month Follow-up Optical Coherence Tomography Imaging | Number of patients with intragraft thrombus seen at 12 month follow-up by optical coherence tomography in imaged saphenous vein graft | In the prasugrel arm, 29 of the 42 patients underwent SVG angiography at 12 months (2 died, 11 did not want to undergo SVG angiography). Of these, 25 had interpretable OCT. In the placebo arm, 30 of the 42 patients underwent SVG angiography at 12 months (1 died, 11 did not wish to undergo SVG angiography). Of these, 28 had interpretable OCT. | Posted | Count of Participants | Participants | 12 months |
|
12 months
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Arm 1: Prasugrel | prasugrel 10 mg by mouth daily Prasugrel: one 10 mg tablet by mouth daily |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Severe GUSTO bleeding | Blood and lymphatic system disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Shuaib Abdullah | VA North Texas Healthcare System | 214-857-1458 | shuaib.abdullah@va.gov |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Dec 12, 2012 | May 21, 2019 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D013927 | Thrombosis |
| ID | Term |
|---|---|
| D016769 | Embolism and Thrombosis |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
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| ID | Term |
|---|---|
| D000068799 | Prasugrel Hydrochloride |
| ID | Term |
|---|---|
| D013876 | Thiophenes |
| D013457 | Sulfur Compounds |
| D009930 | Organic Chemicals |
| D010879 | Piperazines |
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| Placebo | Drug | placebo similar in appearance to prasugrel |
|
Number of patients with angiographic saphenous vein graft failure (defined as =75% SVG diameter stenosis in at least one saphenous vein graft) |
| 12 months |
| Total Target Saphenous Vein Graft Atheroma Volume, as Assessed by Intravascular Ultrasonography | Total target saphenous vein graft atheroma volume (mm3) as assessed by Intravascular ultrasound imaging in imaged saphenous vein grafts. | 12 months |
| Saphenous Vein Graft Lipid Core Burden Index, as Assessed at Near-infrared Intracoronary Spectroscopy | Lipid core burden as measured by Lipid Core Burden Index on near infrared intracoronary spectroscopy imaging of saphenous vein graft. Lipid Core Burden Index is defined as the fraction of pixels within the scanned region with a probability >0.60 that a lipid core plaque is present (calculated by an algorithm developed to identify the NIRS signals associated with the molecular structure of lipids), multiplied by 1000 using EchoPlaque software (INDEC Medical Systems; Los Altos, CA) . Thus, the lipid core burden index (LCBI) is a quantitative summary metric of the probability of the presence of lipid within the scanned region, with a range of 0-1000, with higher indices indicating a higher proportion of pixels with a >0.6 probability of lipid being present in the pullback of the catheter along the length of the entire vessel. | 12 months |
| Major Adverse Cardiac Events, Defined as the Composite of Death, Acute Coronary Syndrome, or Coronary Revascularization) During Follow-up | Number of patients with the composite outcome of death, acute coronary syndrome, or coronary revascularization. | 12 months |
| Normalized Total Target Saphenous Vein Graft Atheroma Volume, as Assessed by Intravascular Ultrasonography | On IVUS images, atheroma volume was defined as the sum of the cross-sectional areas between the leading edges of the lumen and external elastic membrane. Total Target SVG atheroma volume was calculated as: ∑(EEM area - Lumen area). Normalized atheroma volume represents the atheroma volume corrected for pullback length, and this parameter was calculated as: ∑(EEM area - Lumen area)/number of frames in pullback | 12 months |
| North Florida/South Georgia Veterans Health System, Gainesville, FL |
| Gainesville |
| Florida |
| 32608 |
| United States |
| Jesse Brown VA Medical Center Community-Based Outpatient Clinic Lake Side Divison, Chicago, IL | Chicago | Illinois | 60611 | United States |
| VA North Texas Health Care System Dallas VA Medical Center, Dallas, TX | Dallas | Texas | 75216 | United States |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants | No |
|
| Arm 2: Placebo |
placebo by mouth once daily Placebo: placebo similar in appearance to prasugrel |
|
|
|
| Secondary | Number of Patients With Severe Bleeding Using the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO) Criteria | Number of patients with major bleeding defined by the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries criteria. | Posted | Count of Participants | Participants | 12 months |
|
|
|
|
| Secondary | Number of Patients With Angiographic Saphenous Vein Graft Failure | Number of patients with angiographic saphenous vein graft failure (defined as =75% SVG diameter stenosis in at least one saphenous vein graft) | In the prasugrel arm, 29 of the 42 patients underwent SVG angiography at 12 months (2 died, 11 did not want to undergo SVG angiography). In the placebo arm, 30 of the 42 patients underwent SVG angiography at 12 months (1 died, 11 did not wish to undergo SVG angiography). | Posted | Count of Participants | Participants | 12 months |
|
|
|
|
| Secondary | Total Target Saphenous Vein Graft Atheroma Volume, as Assessed by Intravascular Ultrasonography | Total target saphenous vein graft atheroma volume (mm3) as assessed by Intravascular ultrasound imaging in imaged saphenous vein grafts. | In the prasugrel arm, 29 of the 42 patients underwent SVG angiography at 12 months (2 died, 11 did not want to undergo SVG angiography). Of these, 25 had interpretable IVUS. In the placebo arm, 30 of the 42 patients underwent SVG angiography at 12 months (1 died, 11 did not wish to undergo SVG angiography). Of these, 27 had interpretable IVUS. | Posted | Mean | Standard Deviation | mm3 | 12 months |
|
|
|
|
| Secondary | Saphenous Vein Graft Lipid Core Burden Index, as Assessed at Near-infrared Intracoronary Spectroscopy | Lipid core burden as measured by Lipid Core Burden Index on near infrared intracoronary spectroscopy imaging of saphenous vein graft. Lipid Core Burden Index is defined as the fraction of pixels within the scanned region with a probability >0.60 that a lipid core plaque is present (calculated by an algorithm developed to identify the NIRS signals associated with the molecular structure of lipids), multiplied by 1000 using EchoPlaque software (INDEC Medical Systems; Los Altos, CA) . Thus, the lipid core burden index (LCBI) is a quantitative summary metric of the probability of the presence of lipid within the scanned region, with a range of 0-1000, with higher indices indicating a higher proportion of pixels with a >0.6 probability of lipid being present in the pullback of the catheter along the length of the entire vessel. | In the prasugrel arm, 29 of the 42 patients underwent SVG angiography at 12 months (2 died, 11 did not want to undergo SVG angiography). Of these, 12 had interpretable NIRS. In the placebo arm, 30 of the 42 patients underwent SVG angiography at 12 months (1 died, 11 did not wish to undergo SVG angiography). Of these, 20 had interpretable NIRS. | Posted | Mean | Standard Deviation | units on a scale | 12 months |
|
|
|
|
| Secondary | Major Adverse Cardiac Events, Defined as the Composite of Death, Acute Coronary Syndrome, or Coronary Revascularization) During Follow-up | Number of patients with the composite outcome of death, acute coronary syndrome, or coronary revascularization. | Posted | Count of Participants | Participants | 12 months |
|
|
|
| Secondary | Normalized Total Target Saphenous Vein Graft Atheroma Volume, as Assessed by Intravascular Ultrasonography | On IVUS images, atheroma volume was defined as the sum of the cross-sectional areas between the leading edges of the lumen and external elastic membrane. Total Target SVG atheroma volume was calculated as: ∑(EEM area - Lumen area). Normalized atheroma volume represents the atheroma volume corrected for pullback length, and this parameter was calculated as: ∑(EEM area - Lumen area)/number of frames in pullback | In the prasugrel arm, 29 of the 42 patients underwent SVG angiography at 12 months (2 died, 11 did not want to undergo SVG angiography). Of these, 25 had interpretable IVUS. In the placebo arm, 30 of the 42 patients underwent SVG angiography at 12 months (1 died, 11 did not wish to undergo SVG angiography). Of these, 27 had interpretable IVUS. | Posted | Mean | Standard Deviation | mm3/frame | 12 months |
|
|
|
|
| 2 |
| 42 |
| 9 |
| 42 |
| 0 |
| 42 |
| EG001 | Arm 2: Placebo | placebo by mouth once daily Placebo: placebo similar in appearance to prasugrel | 1 | 42 | 4 | 42 | 0 | 42 |
| Death | General disorders | Systematic Assessment |
|
| Acute coronary syndrome | Cardiac disorders | Systematic Assessment |
|
| Percutaneous Coronary Intervention | Cardiac disorders | Systematic Assessment |
|
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| D006573 |
| Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |