Veliflapon (DG-031)to Prevent Heart Attacks or Stroke in Patients With a History of Heart Attack or Unstable Angina - Full Text View

Sponsor:	deCODE genetics
Collaborators:	Henry Ford Coordinating Center Duke University
Information provided by:	deCODE genetics
ClinicalTrials.gov Identifier:	NCT00353067

Purpose

The purpose of this study is to determine if veliflapon (DG-031)can prevent a heart attack or stroke in African American patients with a history of unstable angina or myocardial infarction.

Condition	Intervention	Phase
Acute Coronary Syndrome	Drug: veliflapon (DG-031)	Phase III

Study Type:	Interventional
Study Design:	Prevention, Randomized, Double-Blind, Placebo Control, Parallel Assignment, Safety/Efficacy Study
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).

Resource links provided by NLM:

MedlinePlus related topics: Angina Heart Attack

U.S. FDA Resources

Further study details as provided by deCODE genetics:

Primary Outcome Measures:

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

Secondary Outcome Measures:

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.

Estimated Enrollment:	3450
Study Start Date:	May 2006

Detailed Description:

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).

Eligibility

Ages Eligible for Study:	35 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Men and women
35 years of age or older
African American by self-report.
A history of either acute MI or admission for unstable angina (UA)within 30 days of randomization
Women who have undergone surgical sterilization (hysterectomy or bilateral tubal ligation or bilateral oophorectomy)or are > 2 years post-menopausal by medical history are also eligible.
Women of childbearing potential must have a negative urine pregnancy test and are required to use 2 barrier methods of contraception throughout the study.
Patients are capable of understanding study procedures and agree to participate in the study including scheduled follow up visits and consent to genetic haplotype testing.

Exclusion Criteria:

Presence of active, symptomatic HF defined by presence of New York Heart Association Class II-IV at time of screening.
Received any treatment with an investigational agent or device within 4 weeks.
Evidence of secondary angina or ischemia
Underlying cardiac disorders that may cause cardiac ischemia including aortic stenosis or hypertrophic cardiomyopathy.
Presence of active hepatic disease or AST and/or ALT > 3.0 × ULN.
Calculated creatinine clearance < 30 ml/minute OR the presence of chronic and severe renal insufficiency.
Major surgery performed within six weeks prior to scheduled day of randomization.
Any other major intercurrent illness and other condition, which, in the opinion of the Investigator, will interfere with the patient’s participation in the study or leads to a survival prognosis of < 5 years.
A history of additional risk factors for Torsades de Pointe (TdP)
Patients who are not willing to return for follow up visits or with a known history of non-compliance.
Patients who consume > 3 alcoholic drinks/day or > 15 drinks/week, or have a history of alcohol abuse within the past 2 years.
History of active drug abuse within 1 year of screening for the study.
Pregnant or lactating women.
Poor mental function or any other reason that may cause difficulty in complying with the requirements of the study.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00353067

Locations

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

Suffolk, Virginia, United States, 23434

Hopewell, Virginia, United States, 23860

Sponsors and Collaborators

deCODE genetics

Henry Ford Coordinating Center

Duke University

Investigators

Principal Investigator:	Douglas W Weaver, M.D.	Henry Ford Hospital
Principal Investigator:	Christopher Granger, M.D.	Duke University

More Information

No publications provided

Study ID Numbers:	DG-031-CV-301
Study First Received:	July 14, 2006
Last Updated:	November 28, 2006
ClinicalTrials.gov Identifier:	NCT00353067 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by deCODE genetics:

unstable angina
myocardial infarction
coronary thrombosis
coronary atherosclerosis

Additional relevant MeSH terms:

Anti-Inflammatory Agents
Molecular Mechanisms of Pharmacological Action
Myocardial Ischemia
Physiological Effects of Drugs
Angina Pectoris
Pain
Signs and Symptoms
Pathologic Processes
Sensory System Agents
Syndrome
Therapeutic Uses
Cardiovascular Diseases
Anti-Inflammatory Agents, Non-Steroidal
Analgesics

2-(4-(quinolin-2-yl-methoxy)phenyl)-2-cyclopentylacetic acid
Disease
Heart Diseases
Vascular Diseases
Enzyme Inhibitors
Pharmacologic Actions
Lipoxygenase Inhibitors
Chest Pain
Analgesics, Non-Narcotic
Acute Coronary Syndrome
Peripheral Nervous System Agents
Antirheumatic Agents
Central Nervous System Agents
Angina, Unstable

ClinicalTrials.gov processed this record on February 08, 2010