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Aspirin Dose and Atherosclerosis in Patients With Heart Disease (TAD)

Primary Purpose

Cardiovascular Diseases, Atherosclerosis, Myocardial Infarction

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 treatment trial for Cardiovascular Diseases focused on measuring Cardiovascular diseases, Aspirin, Atherosclerosis, Myocardial Infarction

Eligibility Criteria

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

Inclusion Criteria: Age 40 to 80 years, inclusive. Patients with stable coronary disease, with and without diabetes mellitus, defined by: angiographic evidence of 70% or greater stenosis, or previous percutaneous coronary intervention (PCI), or coronary artery bypass graft (CABG), or history of a MI, or positive exercise test Exclusion Criteria: Patients taking greater than 81mg aspirin daily. 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 within 6 months of a coronary intervention, including PCI or CABG. Patients with a planned coronary intervention. Patients taking anti-platelet drugs such as clopidogrel or non-steroidal anti-inflammatory drugs (NSAIDs) or anticoagulant drugs such as warfarin. 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 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 trial 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

  • Florida Cardiovascular Research
  • The Broward Heart Group, P.A.

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.
Heme oxygenase a downstream target of nitric oxide formation

Secondary Outcome Measures

Full Information

First Posted
January 3, 2006
Last Updated
December 4, 2018
Sponsor
Florida Atlantic University
Collaborators
Bayer
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1. Study Identification

Unique Protocol Identification Number
NCT00272337
Brief Title
Aspirin Dose and Atherosclerosis in Patients With Heart Disease
Acronym
TAD
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 & Endothelial Function in Secondary Prevention (Pts w/Chronic Stable Coronary Disease)
Study Type
Interventional

2. Study Status

Record Verification Date
December 2018
Overall Recruitment Status
Completed
Study Start Date
October 2006 (undefined)
Primary Completion Date
June 2009 (Actual)
Study Completion Date
June 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 who have had a 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. 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, Atherosclerosis, Myocardial Infarction
Keywords
Cardiovascular diseases, Aspirin, Atherosclerosis, Myocardial Infarction

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
37 (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
Heme oxygenase a downstream target of nitric oxide 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: Age 40 to 80 years, inclusive. Patients with stable coronary disease, with and without diabetes mellitus, defined by: angiographic evidence of 70% or greater stenosis, or previous percutaneous coronary intervention (PCI), or coronary artery bypass graft (CABG), or history of a MI, or positive exercise test Exclusion Criteria: Patients taking greater than 81mg aspirin daily. 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 within 6 months of a coronary intervention, including PCI or CABG. Patients with a planned coronary intervention. Patients taking anti-platelet drugs such as clopidogrel or non-steroidal anti-inflammatory drugs (NSAIDs) or anticoagulant drugs such as warfarin. 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 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 trial 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
Florida Cardiovascular Research
City
Atlantis
State/Province
Florida
ZIP/Postal Code
33462
Country
United States
Facility Name
The Broward Heart Group, P.A.
City
Tamarac
State/Province
Florida
ZIP/Postal Code
33321
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
5284360
Citation
Vane JR. Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs. Nat New Biol. 1971 Jun 23;231(25):232-5. doi: 10.1038/newbio231232a0. No abstract available.
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.
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PubMed Identifier
9155612
Citation
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Citation
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PubMed Identifier
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Citation
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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.
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PubMed Identifier
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Citation
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Citation
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Citation
Hetzel S, DeMets D, Schneider R, Borzak S, Schneider W, Serebruany V, Schroder H, Hennekens CH. Aspirin increases nitric oxide formation in chronic stable coronary disease. J Cardiovasc Pharmacol Ther. 2013 May;18(3):217-21. doi: 10.1177/1074248413482753. Epub 2013 Mar 21.
Results Reference
derived

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Aspirin Dose and Atherosclerosis in Patients With Heart Disease

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