Prasugrel for Prevention of Early Saphenous Vein Graft Thrombosis

This study is currently recruiting participants.
Verified January 2014 by Department of Veterans Affairs
Sponsor:
Information provided by (Responsible Party):
Department of Veterans Affairs
ClinicalTrials.gov Identifier:
NCT01560780
First received: March 16, 2012
Last updated: January 17, 2014
Last verified: January 2014
  Purpose

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.


Condition Intervention Phase
Coronary Artery Bypass
Drug: Prasugrel
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Prasugrel for Prevention of Early Saphenous Vein Graft Thrombosis

Resource links provided by NLM:


Further study details as provided by Department of Veterans Affairs:

Primary Outcome Measures:
  • prevalence of intragraft thrombus at 12-month follow-up optical coherence tomography imaging [ Time Frame: 12 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • incidence of severe bleeding using the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO) criteria [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
  • incidence of angiographic saphenous vein graft failure [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    angiographic saphenous vein graft failure (defined as =75% SVG diameter stenosis in at least one saphenous vein graft)

  • total target saphenous vein graft atheroma volume, as assessed by intravascular ultrasonography [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • saphenous vein graft lipid core burden index, as assessed at near-infrared intracoronary spectroscopy [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • major adverse cardiac events, defined as the composite of death, acute coronary syndrome, or coronary revascularization) during follow-up [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
  • normalized total target saphenous vein graft atheroma volume, as assessed by intravascular ultrasonography [ Time Frame: 12 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 120
Study Start Date: February 2013
Estimated Study Completion Date: April 2017
Estimated Primary Completion Date: January 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1
prasugrel 10 mg by mouth daily
Drug: Prasugrel
one 10 mg tablet by mouth daily
Other Name: Effient
Placebo Comparator: Arm 2
placebo by mouth once daily
Drug: Placebo
placebo similar in appearance to prasugrel

Detailed Description:

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: We 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:

  1. Reduction of the prevalence of intragraft thrombus at 12-month follow-up optical coherence tomography imaging (primary efficacy endpoint)
  2. Similar incidence of severe bleeding using the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO) criteria (primary safety endpoint)
  3. Reduction in the incidence of angiographic SVG failure (defined as 75% SVG diameter stenosis in at least one SVG); reduction in total and normalized total target saphenous vein graft atheroma volume, as assessed by intravascular ultrasonography; and reduction of saphenous vein graft lipid core burden index, as assessed at near-infrared intracoronary spectroscopy at 12-month follow-up cardiac catheterization (secondary endpoints)
  4. Reduction of major adverse cardiac events, defined as the composite of death, acute coronary syndrome, or coronary revascularization) during follow-up (secondary endpoints)
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age 18 years or greater
  • Willing and able to give informed consent. The patients must be able to comply with study procedures and follow-up.
  • Undergoing clinically-indicated coronary artery bypass graft surgery

Exclusion Criteria:

  • Known allergy to aspirin or prasugrel
  • Need for concomitant cardiac procedure, such as valve repair or replacement
  • Increased risk of bleeding, including need for warfarin or dabigatran administration
  • Positive pregnancy test or breast-feeding
  • Coexisting conditions that limit life expectancy to less than 12 months or that could affect a patient's compliance with the protocol
  • Serum creatinine > 2.5 mg/dL
  • Severe peripheral arterial disease limiting vascular access
  • Prior stroke or transient ischemic attack
  • Weight <60 kg or age >75 years
  • Multiple distal SVG anastomoses
  • Postoperative complications prolonging hospitalization
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01560780

Contacts
Contact: Emmanouil S Brilakis, MD PhD (214) 857-1556 Emmanouil.Brilakis@va.gov
Contact: Subhash Banerjee, MD (214) 857-1608 subhash.banerjee@va.gov

Locations
United States, Texas
VA North Texas Health Care System, Dallas Recruiting
Dallas, Texas, United States, 75216
Contact: James P LePage, PhD    214-857-0240 ext 70240    James.LePage@va.gov   
Principal Investigator: Emmanouil S Brilakis, MD PhD         
Sponsors and Collaborators
Investigators
Principal Investigator: Emmanouil S Brilakis, MD PhD VA North Texas Health Care System, Dallas
  More Information

No publications provided

Responsible Party: Department of Veterans Affairs
ClinicalTrials.gov Identifier: NCT01560780     History of Changes
Other Study ID Numbers: CLIN-007-11F
Study First Received: March 16, 2012
Last Updated: January 17, 2014
Health Authority: United States: Federal Government

Keywords provided by Department of Veterans Affairs:
Coronary Artery Bypass
thrombosis
prasugrel

Additional relevant MeSH terms:
Thrombosis
Embolism and Thrombosis
Vascular Diseases
Cardiovascular Diseases
Prasugrel
Purinergic P2Y Receptor Antagonists
Purinergic P2 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on April 23, 2014