Veliflapon (DG-031)to Prevent Heart Attacks or Stroke in Patients With a History of Heart Attack or Unstable Angina
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Primary Purpose: Prevention
|Official Title:||A Randomized, Double-Blind, Placebo-Controlled Study to Examine the Safety and Efficacy of Veliflapon (DG-031) in Reducing the Risk of Acute Cardiovascular Events in African American Patients With Coronary Artery Disease(The LTCAD Study).|
- Time to first occurrence of a composite endpoint including:hospitalization for unstable angina or urgent revascularization; fatal/non-fatal MI; fatal/non-fatal stroke or CV related death
- Time to first occurrence of each of the following: an acute CV event (one of the composite CV events) among ALL randomized patients; MI, fatal and non-fatal
- Stroke, fatal and non-fatal; CV related death and all cause mortality.
|Study Start Date:||May 2006|
Genetic linkage and association studies in Icelandic patients with a history of myocardial infarction and stroke showed common haplotypes in two genes, 5-lipoxygenase activating protein(FLAP)and Leukotriene A4 Hydrolase(LTA4H), that each conferred significant risk for MI and stroke. The FLAP haplotype had a RR of 1.8 for MI and 2.1 for those with MI and stroke. LTA4H haplotype had a RR of 1.1 for MI and 1.5 for MI and stroke.Both gene associations were replicated in European and US Caucasian groups and were independent of the conventional risk factors such as LDL-cholesterol, hypertension, and diabetes. The haplotype for the LTA4H pathway showed a modest relative risk of 1.2 in US Caucasian cohorts for all MI and 1.4 for MI and stroke. However, the LTA4H haplotype had a much higher relative risk of 3.5 for myocardial infarction in African-Americans (p=0.000022).
Self identified African American patients with acute coronary syndrome (ACS) were selected for this study as this population has the highest risk identified to date for developing an MI related to the HapK genetic variant in the leukotriene pathway. The study will be enriched to include African American patients randomized by an algorithm designed to assure that approximately 80% of the study population will be Hap K positive and 20% will not have the Hap K positive result.
All patients will be screened for eligibility based on the haplotype status. Patients will be randomized to either veliflapon or placebo on top of standard care. Patients are randomized within 5-30 days of their ACS event.
This is an events driven study with the time of the first occurrence of any of the following elements: hospitalization for UA or urgent revascularization, fatal/non-fatal MI, fatal/non-fatal stroke and CV related death comprising the primary endpoint. The primary null hypothesis of efficacy is that time to first CV event among African American patients with a positive LTA4H HapK Variant assay test is no different from placebo when either is given in addition to standard of care therapy. A total of 3450 eligible patients will be randomized in this study.
The treatment duration for patients enrolled in the study will be a target of at least 6 months (based on approximate time of last patient enrolled) and up to 36 months (from first patient enrolled). All cardiac clinical events endpoints will be adjudicated by an independent Clinical Endpoint Committee (CEC).
Please refer to this study by its ClinicalTrials.gov identifier: NCT00353067
|United States, Alabama|
|Montgomery, Alabama, United States, 36106|
|United States, Florida|
|Jacksonville, Florida, United States, 32216|
|United States, Illinois|
|Melrose Park, Illinois, United States, 60160|
|United States, Oklahoma|
|Oklahoma City, Oklahoma, United States, 73103|
|United States, Pennsylvania|
|Philadelphia, Pennsylvania, United States, 19142|
|United States, Tennessee|
|Nashville, Tennessee, United States, 37203|
|United States, Texas|
|Carrollton, Texas, United States, 75007|
|Fort Worth, Texas, United States, 76104|
|Richardson, Texas, United States, 75080|
|United States, Virginia|
|Hopewell, Virginia, United States, 23860|
|Suffolk, Virginia, United States, 23434|
|Principal Investigator:||Douglas W Weaver, M.D.||Henry Ford Hospital|
|Principal Investigator:||Christopher Granger, M.D.||Duke University|