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Investigation of the Athero-Protective Effects of Clopidogrel (APECS)

15 april 2015 uppdaterad av: Arshed A. Quyyumi, Emory University

Phase 4 Study of Clopidogrel in Patients With Stable Coronary Artery Disease to Determine Effects on Vascular Function, Biomarkers and Endothelial Progrenitor Cells

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.

Studieöversikt

Status

Avslutad

Betingelser

Detaljerad beskrivning

Blockages in the blood vessels of the heart are caused by atherosclerosis. Atherosclerosis is the main cause for chest pain and heart attacks. Gradual narrowing of the vessels of the heart caused by blockages causes chronic symptoms, such as chest pain. Those with these findings often have a cardiac catheterization to detect these blockages. Additionally these patients may have an angioplasty or stent placed to help relieve these symptoms. With this angioplasty/stent procedure, patients are placed on the drug clopidogrel to help prevent clots from forming and narrowing of the blood vessels. Clopidogrel is a blood thinner that prevents clots from forming similar to an aspirin, but is more powerful and effective. Markers, or substances, have been identified that cause worsening of the blockages in the blood vessels of the heart. Many of these substances have been shown to decrease with the use of clopidogrel. This occurs separately from clopidogrel's ability to prevent clots. Endothelial progenitor cells, or EPCs, come mostly from the bone marrow and is helpful in repairing damage to the lining of the blood vessels of the heart. The EPCs help balance out the damage incurred in the blood vessels from those harmful markers. Several other drugs commonly used in heart disease have recently been shown to improve EPCs function. With this in mind, it is important to understand more of clopidogrel's function. A decrease in markers that cause worsening of the blockages, and an increase in the number of cells that will help repair damaged blood vessels of the heart is important in avoiding future chest pain and heart attacks. This may be how clopidogrel is currently protecting patients from developing new blockages. 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.

Studietyp

Interventionell

Inskrivning (Faktisk)

48

Fas

  • Fas 4

Kontakter och platser

Det här avsnittet innehåller kontaktuppgifter för dem som genomför studien och information om var denna studie genomförs.

Studieorter

    • Georgia
      • Atlanta, Georgia, Förenta staterna, 30322
        • Emory University Hospital

Deltagandekriterier

Forskare letar efter personer som passar en viss beskrivning, så kallade behörighetskriterier. Några exempel på dessa kriterier är en persons allmänna hälsotillstånd eller tidigare behandlingar.

Urvalskriterier

Åldrar som är berättigade till studier

21 år till 80 år (Vuxen, Äldre vuxen)

Tar emot friska volontärer

Nej

Kön som är behöriga för studier

Allt

Beskrivning

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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.
  • Inability to give informed consent
  • Inability to return to Emory for follow-up

Studieplan

Det här avsnittet ger detaljer om studieplanen, inklusive hur studien är utformad och vad studien mäter.

Hur är studien utformad?

Designdetaljer

  • Primärt syfte: Grundläggande vetenskap
  • Tilldelning: Randomiserad
  • Interventionsmodell: Crossover tilldelning
  • Maskning: Fyrdubbla

Vapen och interventioner

Deltagargrupp / Arm
Intervention / Behandling
Aktiv komparator: Clopidogrel/Placebo
Subjects were randomized to clopidogrel 75 mg daily for 6 weeks. Then immediately transitioned to a placebo daily for 6 weeks.
Clopidogrel 75 mg PO qday for 6 weeks
Andra namn:
  • Plavix
Placebo PO qday for 6 weeks
Aktiv komparator: Placebo/Clopidogrel
Subjects were randomized to a placebo daily for 6 weeks. Then immediately transitioned to clopidogrel 75 mg daily for 6 weeks.
Clopidogrel 75 mg PO qday for 6 weeks
Andra namn:
  • Plavix
Placebo PO qday for 6 weeks

Vad mäter studien?

Primära resultatmått

Resultatmått
Åtgärdsbeskrivning
Tidsram
Flow-mediated Dilation (FMD)
Tidsram: Baseline, Week 12
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
Tidsram: Baseline, Week 12
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)
Tidsram: Week 12
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

Sekundära resultatmått

Resultatmått
Åtgärdsbeskrivning
Tidsram
Pulse Wave Velocity (PWV)
Tidsram: Week 12
PWV was measured between the carotid and femoral arteries using the SphygmoCor device. Pressure waveforms at the carotid and femoral arteries were acquired using EKG gating. Velocity (distance per time in seconds) was calculated using the foot-to-foot method and the distance between the sites was measured manually.
Week 12
Oxidative Stress Markers
Tidsram: Week 12
Oxidative stress was measured by using liquid chromatography to collect plasma cystine, cysteine, gluthione, and oxidized glutathione levels.
Week 12
Inflammatory Marker High-sensitivity C-reactive Protein (hsCRP)
Tidsram: Week 12
High-sensitivity C-reactive protein (hsCRP) was measured. The hsCRP levels were measured by Dade Behring nephelometry.
Week 12
Inflammatory Marker CD40 Ligand
Tidsram: Week 12
CD40 ligand levels were measured. The level of CD40 ligand were measured using the Flurokine MultiAnalyte profiling (MAP) Human Base Kit B.
Week 12

Samarbetspartners och utredare

Det är här du hittar personer och organisationer som är involverade i denna studie.

Utredare

  • Huvudutredare: Ziyad Ghazzal, MD, American University of Beirut, Emory University

Publikationer och användbara länkar

Den som ansvarar för att lägga in information om studien tillhandahåller frivilligt dessa publikationer. Dessa kan handla om allt som har med studien att göra.

Studieavstämningsdatum

Dessa datum spårar framstegen för inlämningar av studieposter och sammanfattande resultat till ClinicalTrials.gov. Studieposter och rapporterade resultat granskas av National Library of Medicine (NLM) för att säkerställa att de uppfyller specifika kvalitetskontrollstandarder innan de publiceras på den offentliga webbplatsen.

Studera stora datum

Studiestart

1 januari 2008

Primärt slutförande (Faktisk)

1 december 2010

Avslutad studie (Faktisk)

1 december 2010

Studieregistreringsdatum

Först inskickad

24 januari 2011

Först inskickad som uppfyllde QC-kriterierna

24 januari 2011

Första postat (Uppskatta)

25 januari 2011

Uppdateringar av studier

Senaste uppdatering publicerad (Uppskatta)

1 maj 2015

Senaste inskickade uppdateringen som uppfyllde QC-kriterierna

15 april 2015

Senast verifierad

1 april 2015

Mer information

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