Aspirin Dose and Atherosclerosis in Patients With Metabolic Syndrome - Full Text View

Sponsors and Collaborators:	Florida Atlantic University Bayer
Information provided by:	Florida Atlantic University
ClinicalTrials.gov Identifier:	NCT00272311

Purpose

The purpose of the study is to test higher versus lower doses of aspirin on markers of atherosclerosis in patients at risk of a first heart attack.

Condition	Intervention	Phase
Cardiovascular Diseases Metabolic Syndrome X Atherosclerosis	Drug: Aspirin	Phase IV

MedlinePlus related topics: Metabolic Syndrome

Drug Information available for: Acetylsalicylic acid Nitric oxide

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Prevention, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Dose Comparison, Parallel Assignment, Safety/Efficacy Study
Official Title:	A Randomized, Double-Blind Trial to Test Higher- Versus Lower-Doses of Aspirin on Inflammatory Markers and Platelet Biomarkers and Nitric Oxide Formation in High Risk Primary Prevention (Patients With Metabolic Syndrome)

Further study details as provided by Florida Atlantic University:

Primary Outcome Measures:

inflammatory markers, measured at baseline and 3 months [ Time Frame: 90-97 days ]
platelet biomarkers, measured at baseline and 3 months [ Time Frame: 90-97 days ]
nitric oxide formation, measured at baseline and 3 months [ Time Frame: 90-97 days ]

Estimated Enrollment:	100
Study Start Date:	October 2006
Estimated Study Completion Date:	June 2008

Arms	Assigned Interventions
1: Active Comparator 81 mg ASA	Drug: Aspirin Dosage
2: Active Comparator 162 mg ASA	Drug: Aspirin Dosage
3: Active Comparator 325 mg ASA	Drug: Aspirin Dosage
4: Active Comparator 650 mg ASA	Drug: Aspirin Dosage
5: Active Comparator 1300 mg ASA	Drug: Aspirin Dosage

Detailed Description:

Aspirin reduces risks of heart attacks, strokes, and deaths from cardiovascular causes in patients who have survived a prior event as well as during an acute heart attack. Aspirin also prevents a first heart attack.

Low dose aspirin is sufficient to achieve complete inhibition of platelet aggregability, or stickiness, and this is the mechanism whereby aspirin prevents formation of blood clots.

Our research is designed to explore whether higher doses of aspirin provide additional benefits on markers of atherosclerosis.

Eligibility

Ages Eligible for Study:	40 Years to 80 Years
Genders Eligible for Study:	Both

Criteria

Inclusion Criteria:

1. Age 40 to 80 years, inclusive.

2. No previous heart attack or a stroke, or other forms of these diseases.

3. Have at least three of the five characteristics listed below, indicating presence of metabolic syndrome, as defined by NCEP-III:
1. waist measuring more than 40 inches (for men) or more than 35 inches (for women),
2. high density lipoprotein (HDL) cholesterol levels lower than 40 milligrams per deciliter (mg/dl) in men or 50 mg/dl in women,
3. triglyceride (TG) levels above 150 mg/dl,
4. blood pressure greater than 130 millimeters of mercury (mmHg) systolic or 85 mmHg diastolic,
5. fasting blood sugar greater than 110 mg/dl

Exclusion Criteria:

Patients taking greater than 81mg aspirin daily.
Patients taking anti-platelet drugs such as clopidogrel or non-steroidal anti-inflammatory drugs (NSAIDs) or anticoagulant drugs such as warfarin, during the last two weeks.
Patients taking any of the following medications for less than 3 months, or who plan to take them for the first time during the next 3 months: ACE-inhibitors, angiotensin receptor blockers, calcium channel blockers, or statins.
Patients who are currently cigarette smokers.
Women patients who are pregnant, planning to become pregnant, nursing a child, or taking hormone replacement therapy.
Patients with any coagulation, bleeding or blood disorders.
Patients who are sensitive or allergic to aspirin.
Patients with documented history of any gastrointestinal disorders, including bleeding ulcers.
Patients with any evidence of cancer or history of significant cardiovascular disease (including heart attack, stroke or drop attacks termed transient ischemic attacks (TIAs), or blockages of the arteries in the legs termed peripheral arterial disease (PAD)), kidney, liver, lung, blood, or brain disorders.
Patients with asthma, rhinitis, or nasal polyps.
Patients with any abnormal laboratory value or physical finding that, in the view of the responsible clinician, may interfere with interpretation of the study results, be indicative of an underlying disease state, or compromise the safety.
Patients with Class IV heart failure.
Patients with severe aortic insufficiency, or aortic regurgitation.
Patients with hearing loss or tinnitus.
Patients with tremors which cause them not to be able to remain motionless for approximately 30 seconds.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00272311

Locations

United States, Maryland
HeartDrug Research, LLC
Towson, Maryland, United States, 21204

Sponsors and Collaborators

Florida Atlantic University

Bayer

Investigators

Principal Investigator:	Charles H Hennekens, MD, DrPH	Florida Atlantic University
Study Director:	Wendy R Schneider, MSN, CCRC	Florida Atlantic University

More Information

Publications:

Williams A, Hennekens CH. The role of aspirin in cardiovascular diseases--forgotten benefits? Expert Opin Pharmacother. 2004 Jan;5(1):109-15. Review.

Hennekens CH, Buring JE, Sandercock P, Collins R, Peto R. Aspirin and other antiplatelet agents in the secondary and primary prevention of cardiovascular disease. Circulation. 1989 Oct;80(4):749-56. Review. No abstract available.

Eidelman RS, Hebert PR, Weisman SM, Hennekens CH. An update on aspirin in the primary prevention of cardiovascular disease. Arch Intern Med. 2003 Sep 22;163(17):2006-10.

Roth GJ, Stanford N, Majerus PW. Acetylation of prostaglandin synthase by aspirin. Proc Natl Acad Sci U S A. 1975 Aug;72(8):3073-6.

Patrignani P, Filabozzi P, Patrono C. Selective cumulative inhibition of platelet thromboxane production by low-dose aspirin in healthy subjects. J Clin Invest. 1982 Jun;69(6):1366-72. No abstract available.

Reilly IA, FitzGerald GA. Inhibition of thromboxane formation in vivo and ex vivo: implications for therapy with platelet inhibitory drugs. Blood. 1987 Jan;69(1):180-6.

Mustard JF, Packham MA. The role of blood and platelets in atherosclerosis and the complications of atherosclerosis. Thromb Diath Haemorrh. 1975 Jun 30;33(3):444-56.

Mustard JF, Moore S, Packham MA, Kinlough-Rathbone RL. Platelets, thrombosis and atherosclerosis. Prog Biochem Pharmacol. 1977;13:312-25.

Mustard JF, Packham MA, Kinlough-Rathbone RL. Platelets and thrombosis in the development of atherosclerosis and its complications. Adv Exp Med Biol. 1978;102:7-30. Review. No abstract available.

Ikonomidis I, Andreotti F, Economou E, Stefanadis C, Toutouzas P, Nihoyannopoulos P. Increased proinflammatory cytokines in patients with chronic stable angina and their reduction by aspirin. Circulation. 1999 Aug 24;100(8):793-8.

Ridker PM, Cushman M, Stampfer MJ, Tracy RP, Hennekens CH. Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men. N Engl J Med. 1997 Apr 3;336(14):973-9. Erratum in: N Engl J Med 1997 Jul 31;337(5):356.

Hennekens CH, Schror K, Weisman S, FitzGerald GA. Terms and conditions: semantic complexity and aspirin resistance. Circulation. 2004 Sep 21;110(12):1706-8. Review. No abstract available.

Steer KA, Wallace TM, Bolton CH, Hartog M. Aspirin protects low density lipoprotein from oxidative modification. Heart. 1997 Apr;77(4):333-7.

Wu R, Lamontagne D, de Champlain J. Antioxidative properties of acetylsalicylic Acid on vascular tissues from normotensive and spontaneously hypertensive rats. Circulation. 2002 Jan 22;105(3):387-92.

Oberle S, Polte T, Abate A, Podhaisky HP, Schroder H. Aspirin increases ferritin synthesis in endothelial cells: a novel antioxidant pathway. Circ Res. 1998 May 18;82(9):1016-20.

Grosser N, Abate A, Oberle S, Vreman HJ, Dennery PA, Becker JC, Pohle T, Seidman DS, Schroder H. Heme oxygenase-1 induction may explain the antioxidant profile of aspirin. Biochem Biophys Res Commun. 2003 Sep 5;308(4):956-60.

Hennekens CH, Dyken ML, Fuster V. Aspirin as a therapeutic agent in cardiovascular disease: a statement for healthcare professionals from the American Heart Association. Circulation. 1997 Oct 21;96(8):2751-3. No abstract available.

U.S. Preventive Services Task Force. Aspirin for the primary prevention of cardiovascular events: recommendation and rationale. Ann Intern Med. 2002 Jan 15;136(2):157-60. Summary for patients in: Ann Intern Med. 2002 Jan 15;136(2):I55.

Hennekens CH, Hollar D, Baigent C. Sex-related differences in response to aspirin in cardiovascular disease: an untested hypothesis. Nat Clin Pract Cardiovasc Med. 2006 Jan;3(1):4-5. No abstract available.

Pearson TA, Blair SN, Daniels SR, Eckel RH, Fair JM, Fortmann SP, Franklin BA, Goldstein LB, Greenland P, Grundy SM, Hong Y, Miller NH, Lauer RM, Ockene IS, Sacco RL, Sallis JF Jr, Smith SC Jr, Stone NJ, Taubert KA. AHA Guidelines for Primary Prevention of Cardiovascular Disease and Stroke: 2002 Update: Consensus Panel Guide to Comprehensive Risk Reduction for Adult Patients Without Coronary or Other Atherosclerotic Vascular Diseases. American Heart Association Science Advisory and Coordinating Committee. Circulation. 2002 Jul 16;106(3):388-91. Review. No abstract available.

Study ID Numbers:	H07-28
Study First Received:	January 3, 2006
Last Updated:	October 25, 2007
ClinicalTrials.gov Identifier:	NCT00272311
Health Authority:	United States: Institutional Review Board

Keywords provided by Florida Atlantic University:

Primary prevention
Cardiovascular diseases
Aspirin
Metabolic Syndrome X
Atherosclerosis

Study placed in the following topic categories:

Atherosclerosis
Arterial Occlusive Diseases
Metabolic Syndrome X
Metabolic Diseases
Vascular Diseases
Arteriosclerosis
Nitric Oxide

Hyperinsulinism
Aspirin
Syndrome X
Insulin Resistance
Glucose Metabolism Disorders
Metabolic disorder
Abdominal obesity metabolic syndrome

Additional relevant MeSH terms:

Anti-Inflammatory Agents
Disease
Molecular Mechanisms of Pharmacological Action
Cyclooxygenase Inhibitors
Hematologic Agents
Physiological Effects of Drugs
Enzyme Inhibitors
Fibrinolytic Agents
Cardiovascular Agents
Pharmacologic Actions
Fibrin Modulating Agents
Pathologic Processes

Analgesics, Non-Narcotic
Sensory System Agents
Syndrome
Therapeutic Uses
Platelet Aggregation Inhibitors
Cardiovascular Diseases
Anti-Inflammatory Agents, Non-Steroidal
Analgesics
Peripheral Nervous System Agents
Antirheumatic Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on January 16, 2009