Aspirin Dose and Atherosclerosis in Patients With Metabolic Syndrome

NCT00272311 | Completed Phase 4 Results DMC

• 1 other identifier: H08-35
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Cardiovascular Diseases; Metabolic Syndrome X; Atherosclerosis

Keywords

Primary prevention; Cardiovascular diseases; Aspirin; Metabolic Syndrome X; Atherosclerosis

Outcome Measures

Primary Outcomes (1)

• Change in Nitric Oxide Formation From Baseline to 3 Months

  Changes in Heme oxygenase (HO-1) a downstream target of nitric oxide (NO) formation.

  Baseline to 3 Months (90-97 days)

Other Outcomes (2)

• Change in Inflammatory Markers From Baseline to 3 Months.

  Baseline to 3 Months (90-97 days)

• Change in Platelet Biomarkers From Baseline to 3 Months.

  Baseline to 3 Months (90-97 days)

Study Arms (5)

1

ACTIVE COMPARATOR

81 mg Aspirin

Drug: Aspirin

2

ACTIVE COMPARATOR

162 mg Aspirin

Drug: Aspirin

3

ACTIVE COMPARATOR

325 mg Aspirin

Drug: Aspirin

4

ACTIVE COMPARATOR

650 mg Aspirin

Drug: Aspirin

5

ACTIVE COMPARATOR

1300 mg Aspirin

Drug: Aspirin

Interventions

Aspirin DRUG

Dosage

1; 2; 3; 4; 5

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. Age 40 to 80 years, inclusive.
• \. No previous heart attack or a stroke, or other forms of these diseases.
• \. Have at least three of the five characteristics listed below, indicating presence of metabolic syndrome, as defined by NCEP-III:
• waist measuring more than 40 inches (for men) or more than 35 inches (for women),
• high density lipoprotein (HDL) cholesterol levels lower than 40 milligrams per deciliter (mg/dl) in men or 50 mg/dl in women,
• triglyceride (TG) levels above 150 mg/dl,
• blood pressure greater than 130 millimeters of mercury (mmHg) systolic or 85 mmHg diastolic,
• fasting blood sugar greater than 110 mg/dl

You may not qualify if:

• 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.

Sponsors & Collaborators

• Florida Atlantic University: lead
• Bayer: collaborator

Study Sites (1)

HeartDrug Research, LLC

Towson, Maryland, 21204, United States

Location

Related Publications (20)

• Williams A, Hennekens CH. The role of aspirin in cardiovascular diseases--forgotten benefits? Expert Opin Pharmacother. 2004 Jan;5(1):109-15. doi: 10.1517/14656566.5.1.109.

  PMID: 14680440 BACKGROUND

• 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. doi: 10.1161/01.cir.80.4.749. No abstract available.

  PMID: 2676237 BACKGROUND

• 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. doi: 10.1001/archinte.163.17.2006.

  PMID: 14504112 BACKGROUND

• 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. doi: 10.1073/pnas.72.8.3073.

  PMID: 810797 BACKGROUND

• 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. doi: 10.1172/jci110576.

  PMID: 7045161 BACKGROUND

• 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.

  PMID: 3790723 BACKGROUND

• 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.

  PMID: 1154306 BACKGROUND

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

  PMID: 928433 BACKGROUND

• 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. doi: 10.1007/978-1-4757-1217-9_2. No abstract available.

  PMID: 356564 BACKGROUND

• 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. doi: 10.1161/01.cir.100.8.793.

  PMID: 10458713 BACKGROUND

• 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. doi: 10.1056/NEJM199704033361401.

  PMID: 9077376 BACKGROUND

• Hennekens CH, Schror K, Weisman S, FitzGerald GA. Terms and conditions: semantic complexity and aspirin resistance. Circulation. 2004 Sep 21;110(12):1706-8. doi: 10.1161/01.CIR.0000142056.69970.DB. No abstract available.

  PMID: 15381661 BACKGROUND

• Steer KA, Wallace TM, Bolton CH, Hartog M. Aspirin protects low density lipoprotein from oxidative modification. Heart. 1997 Apr;77(4):333-7. doi: 10.1136/hrt.77.4.333.

  PMID: 9155612 BACKGROUND

• 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. doi: 10.1161/hc0302.102609.

  PMID: 11804997 BACKGROUND

• 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. doi: 10.1161/01.res.82.9.1016.

  PMID: 9598599 BACKGROUND

• 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. doi: 10.1016/s0006-291x(03)01504-3.

  PMID: 12927812 BACKGROUND

• 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. doi: 10.1161/01.cir.96.8.2751. No abstract available.

  PMID: 9355934 BACKGROUND

• 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. doi: 10.7326/0003-4819-136-2-200201150-00015.

  PMID: 11790071 BACKGROUND

• 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. doi: 10.1038/ncpcardio0420. No abstract available.

  PMID: 16391594 BACKGROUND

• 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. doi: 10.1161/01.cir.0000020190.45892.75. No abstract available.

  PMID: 12119259 BACKGROUND

MeSH Terms

Conditions

Cardiovascular Diseases; Metabolic Syndrome; Atherosclerosis

Interventions

Aspirin

Condition Hierarchy (Ancestors)

Insulin Resistance; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases

Intervention Hierarchy (Ancestors)

Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Results Point of Contact

• Title: Charles H. Hennekens, M.D.
• Organization: Florida Atlantic University

chenneke@fau.edu

Study Officials

• Charles H Hennekens, MD, DrPH

  Florida Atlantic University

  PRINCIPAL INVESTIGATOR

• Wendy R Schneider, MSN, CCRC

  Florida Atlantic University

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 3, 2006
• First Posted: January 5, 2006
• Study Start: October 1, 2006
• Primary Completion: January 1, 2009
• Study Completion: January 1, 2009
• Last Updated: February 27, 2019
• Results First Posted: June 19, 2012

Record last verified: 2019-02

Locations

US (1)