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Aspirin Dose and Atherosclerosis in Patients With Metabolic Syndrome (PAD)

Primary Purpose

Cardiovascular Diseases, Metabolic Syndrome X, Atherosclerosis

Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Aspirin
Sponsored by
Florida Atlantic University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Cardiovascular Diseases focused on measuring Primary prevention, Cardiovascular diseases, Aspirin, Metabolic Syndrome X, Atherosclerosis

Eligibility Criteria

40 Years - 80 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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: 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 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.

Sites / Locations

  • HeartDrug Research, LLC

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Active Comparator

Active Comparator

Active Comparator

Active Comparator

Active Comparator

Arm Label

1

2

3

4

5

Arm Description

81 mg Aspirin

162 mg Aspirin

325 mg Aspirin

650 mg Aspirin

1300 mg Aspirin

Outcomes

Primary Outcome Measures

Change in Nitric Oxide Formation From Baseline to 3 Months
Changes in Heme oxygenase (HO-1) a downstream target of nitric oxide (NO) formation.

Secondary Outcome Measures

Full Information

First Posted
January 3, 2006
Last Updated
February 5, 2019
Sponsor
Florida Atlantic University
Collaborators
Bayer
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1. Study Identification

Unique Protocol Identification Number
NCT00272311
Brief Title
Aspirin Dose and Atherosclerosis in Patients With Metabolic Syndrome
Acronym
PAD
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)
Study Type
Interventional

2. Study Status

Record Verification Date
February 2019
Overall Recruitment Status
Completed
Study Start Date
October 2006 (undefined)
Primary Completion Date
January 2009 (Actual)
Study Completion Date
January 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Florida Atlantic University
Collaborators
Bayer

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cardiovascular Diseases, Metabolic Syndrome X, Atherosclerosis
Keywords
Primary prevention, Cardiovascular diseases, Aspirin, Metabolic Syndrome X, Atherosclerosis

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
70 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Active Comparator
Arm Description
81 mg Aspirin
Arm Title
2
Arm Type
Active Comparator
Arm Description
162 mg Aspirin
Arm Title
3
Arm Type
Active Comparator
Arm Description
325 mg Aspirin
Arm Title
4
Arm Type
Active Comparator
Arm Description
650 mg Aspirin
Arm Title
5
Arm Type
Active Comparator
Arm Description
1300 mg Aspirin
Intervention Type
Drug
Intervention Name(s)
Aspirin
Intervention Description
Dosage
Primary Outcome Measure Information:
Title
Change in Nitric Oxide Formation From Baseline to 3 Months
Description
Changes in Heme oxygenase (HO-1) a downstream target of nitric oxide (NO) formation.
Time Frame
Baseline to 3 Months (90-97 days)
Other Pre-specified Outcome Measures:
Title
Change in Inflammatory Markers From Baseline to 3 Months.
Time Frame
Baseline to 3 Months (90-97 days)
Title
Change in Platelet Biomarkers From Baseline to 3 Months.
Time Frame
Baseline to 3 Months (90-97 days)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
40 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility 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: 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 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Charles H Hennekens, MD, DrPH
Organizational Affiliation
Florida Atlantic University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Wendy R Schneider, MSN, CCRC
Organizational Affiliation
Florida Atlantic University
Official's Role
Study Director
Facility Information:
Facility Name
HeartDrug Research, LLC
City
Towson
State/Province
Maryland
ZIP/Postal Code
21204
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
14680440
Citation
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.
Results Reference
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PubMed Identifier
2676237
Citation
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.
Results Reference
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PubMed Identifier
14504112
Citation
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.
Results Reference
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PubMed Identifier
810797
Citation
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.
Results Reference
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PubMed Identifier
7045161
Citation
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.
Results Reference
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PubMed Identifier
3790723
Citation
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.
Results Reference
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PubMed Identifier
1154306
Citation
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.
Results Reference
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PubMed Identifier
928433
Citation
Mustard JF, Moore S, Packham MA, Kinlough-Rathbone RL. Platelets, thrombosis and atherosclerosis. Prog Biochem Pharmacol. 1977;13:312-25.
Results Reference
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PubMed Identifier
356564
Citation
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.
Results Reference
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PubMed Identifier
10458713
Citation
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.
Results Reference
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PubMed Identifier
9077376
Citation
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. Erratum In: N Engl J Med 1997 Jul 31;337(5):356.
Results Reference
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PubMed Identifier
15381661
Citation
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.
Results Reference
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PubMed Identifier
9155612
Citation
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.
Results Reference
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PubMed Identifier
11804997
Citation
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Results Reference
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PubMed Identifier
9598599
Citation
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.
Results Reference
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PubMed Identifier
12927812
Citation
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.
Results Reference
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PubMed Identifier
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Citation
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.
Results Reference
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PubMed Identifier
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Citation
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.
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Citation
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.
Results Reference
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PubMed Identifier
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Citation
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.
Results Reference
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Aspirin Dose and Atherosclerosis in Patients With Metabolic Syndrome

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