Investigation of the Athero-Protective Effects of Clopidogrel

NCT01283282 | Completed Phase 4 Results

• 2 other identifiers: IRB00005145APECS
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

The investigators would like to investigate whether clopidogrel will help lower the level of harmful markers in patients with coronary artery disease, and at the same time will help increase the cells that are useful in repairing the damaged blood vessels. The investigators will give half of the patients clopidogrel and the other half a sugar pill, placebo, and check the levels of these markers and helpful cells in each group. At the same time the investigators will check how well these patient's blood vessels work using ultrasound imaging of the forearm to see how blood vessels relax and tonometry to see how stiff the patient's blood vessels are. After 6 weeks of drug therapy, the patients will switch to the other drug and these same tests will be performed after an additional 6 weeks of therapy. The drug taken by the patient will not be known to the patient or the researchers. The patients will continue on their prescribed medical therapy during the duration of the 12 week study.

Conditions

Coronary Artery Disease

Outcome Measures

Primary Outcomes (3)

• Flow-mediated Dilation (FMD)

  Flow-mediated dilation (FMD) collected by an ultrasound and is measured by the percent change in diameter of the brachial artery from baseline to 12 weeks.

  Baseline, Week 12

• Nitroglycerin-mediated Vasodilation

  Nitroglycerin (NTG)-mediated vasodilation was measured after 0.4 mg of NTG was administered sublingually. Brachial artery images were obtained via ultrasound after three minutes of NTG administration. Measurements from the twelve frames will be averaged to calculate the percent change in diameter of the brachial artery from baseline to 12 weeks.

  Baseline, Week 12

• Endothelial Progenitor Cells (EPCs)

  The circulating progenitor-enriched population of cells was measured by the expression of surface antigens using direct flow cytometry for CD34+, CD34+/CD133+, CD34+/ VEGF2R+ and CD34+/CD133+/VEGF2R+

  Week 12

Secondary Outcomes (4)

• Pulse Wave Velocity (PWV)

  Week 12

• Oxidative Stress Markers

  Week 12

• Inflammatory Marker High-sensitivity C-reactive Protein (hsCRP)

  Week 12

• Inflammatory Marker CD40 Ligand

  Week 12

Study Arms (2)

Clopidogrel/Placebo

ACTIVE COMPARATOR

Subjects were randomized to clopidogrel 75 mg daily for 6 weeks. Then immediately transitioned to a placebo daily for 6 weeks.

Drug: Clopidogrel; Drug: Placebo

Placebo/Clopidogrel

ACTIVE COMPARATOR

Subjects were randomized to a placebo daily for 6 weeks. Then immediately transitioned to clopidogrel 75 mg daily for 6 weeks.

Drug: Clopidogrel; Drug: Placebo

Interventions

Clopidogrel DRUG

Clopidogrel 75 mg PO qday for 6 weeks

Also known as: Plavix

Clopidogrel/Placebo; Placebo/Clopidogrel

Placebo DRUG

Placebo PO qday for 6 weeks

Clopidogrel/Placebo; Placebo/Clopidogrel

Eligibility Criteria

• Age: 21 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or females without child bearing potential aged 21-80 years
• Known coronary artery disease by angiogram or documented myocardial infarction.
• Able to provide written informed consent

You may not qualify if:

• Treated with clopidogrel or ticlodipine in the previous 3 months
• Age \< 21 or \>80 years
• Premenopausal females with potential for pregnancy
• Allergy to clopidogrel or aspirin
• Initiation or change in dose of any concomitant medical therapy within 2 months before the study
• Uncontrolled hypertension with BP\>180 mmHg systolic and \>120 mmHg diastolic
• Treated with coumadin therapy
• Intolerance or allergy to statins
• Acute infection in previous 4 weeks
• History of substance abuse
• Uninterpretable PAT test
• Current neoplasm
• Chronic renal failure \[creatinine \> 2.5 mg/dL\] or liver failure (Liver enzymes \>2X normal)
• Acute coronary syndrome, heart failure, CVA, coronary intervention within 3 months
• Known aortic stenosis, hypertrophic cardiomyopathy, symptomatic heart failure.

Sponsors & Collaborators

• Emory University: lead

Study Sites (1)

Emory University Hospital

Atlanta, Georgia, 30322, United States

Location

Related Publications (1)

• Ramadan R, Dhawan SS, Syed H, Pohlel FK, Binongo JN, Ghazzal ZB, Quyyumi AA. Effects of clopidogrel therapy on oxidative stress, inflammation, vascular function, and progenitor cells in stable coronary artery disease. J Cardiovasc Pharmacol. 2014 Apr;63(4):369-74. doi: 10.1097/FJC.0000000000000057.

  PMID: 24336012 DERIVED

MeSH Terms

Conditions

Coronary Artery Disease

Interventions

Clopidogrel

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases

Intervention Hierarchy (Ancestors)

Ticlopidine; Thienopyridines; Thiophenes; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Limitations and Caveats

Limited sample size

Results Point of Contact

• Title: Dr. Arshed Quyyumi
• Organization: Emory University

aquyyum@emory.edu

404-727-3655

Study Officials

• Arshed A Quyyumi, MD

  Emory University

  PRINCIPAL INVESTIGATOR

• Ziyad Ghazzal, MD

  American University of Beirut, Emory University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: January 24, 2011
• First Posted: January 25, 2011
• Study Start: January 1, 2008
• Primary Completion: December 1, 2010
• Study Completion: December 1, 2010
• Last Updated: May 1, 2015
• Results First Posted: May 1, 2015

Record last verified: 2015-04

Locations

US (1)