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Endothelium, Stenting, and Antiplatelet Therapy (EST) - Clopidogrel, Prasugrel, Ticagrelor Study (EST)

4. september 2016 oppdatert av: Tommaso Gori, Johannes Gutenberg University Mainz

Effects of Clopidogrel vs Prasugel vs Ticagrelor on Endothelial Function, Inflammatory and Oxidative Stress Parameters and Platelet Function in Patients Undergoing Coronary Artery Stenting. A Randomised, Prospective Study.

Endothelial dysfunction is an important predictor - and a determinant - of adverse clinical outcome. Endothelial function is impaired by coronary artery stenting, a stud from our group has shown that it can be improved by platelet inhibition using clopidogrel. However, clopidogrel unresponsiveness is a known problem, and it has been show that the endothelial effects of clopidogrel tend to wane upon prolonged treatment. Whether a more effective anti-platelet therapy is able to prevent/improve not only thrombotic events but also endothelial dysfunction, with potential positive impact on clinical outcome in patients undergoing coronary artery stenting, is an important hypothesis that needs to be further investigated. To date, evidence regarding "ancillary" (non-platelet-dependent) effects of antiaggregant drugs is very limited. For instance, while their antiplatelet effects, and their beneficial effects in patients with acute coronary syndromes, have been clearly demonstrated in multicentric trials, it remains to be shown whether these drugs also protect endothelial function. Interestingly, some authors suggest that the mortality benefit observed in the PLATO study is at least in part independent of direct antiplatelet effects. No study, to date, has tested the effects of prasugrel and/or ticagrelor on endothelial function. With the present trial, the investigators plan to test the effect of clopidogrel, prasugrel and ticagrelor on endothelial function before and up to 4 weeks after coronary artery stenting. This study will provide important pathophysiologic insight on the relationship between platelet aggregation and endothelial function, two parameters that have been shown to influence patients' prognosis.

Studieoversikt

Studietype

Intervensjonell

Registrering (Faktiske)

126

Fase

  • Fase 4

Kontakter og plasseringer

Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.

Studiesteder

      • Mainz, Tyskland, 55131
        • 2 Medical Clinic

Deltakelseskriterier

Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.

Kvalifikasjonskriterier

Alder som er kvalifisert for studier

18 år til 75 år (Voksen, Eldre voksen)

Tar imot friske frivillige

Nei

Kjønn som er kvalifisert for studier

Alle

Beskrivelse

Inclusion Criteria:

  • - 18-75 years old consecutive patients undergoing coronary angiography and stenting at the University Medical Centre Mainz
  • A coronary lesion (and patient) amenable to treatment with drug eluting stent
  • Ability of subject to understand character and individual consequences of clinical trial
  • Signed and dated informed consent of the subject must be available before start of any specific trial procedures.
  • Negative pregnancy test of women with childbearing potential

Exclusion Criteria:

  • Subjects presenting 1 or more of the following criteria will not be enrolled in the trial:
  • Patients with elevated (> 5 times upper normal limit) C-reactive protein level prior to stenting
  • Patients in whom therapy with long-acting nitrates cannot be suspended prior to endothelial function measurements
  • An acute coronary syndrome treated with coronary stenting within the last 4 weeks
  • Patients with known inflammatory/infective diseases
  • Patients with severe extracardiac diseases limiting life expectancy
  • Known heart failure (LV-EF ≤ 40% AND NYHA III-IV)
  • PCI or coronary By-Pass surgery within the last 4 weeks, pre-existing ongoing treatment with any of the study treatments.
  • History of cerebrovascular events (stroke)
  • Known renal dysfunction (serum creatinine ≥ 1.8mg/dl in women, ≥ 2.0mg/dl in men)
  • Serum potassium > 5.5mmol/l
  • Known hepatic impairment (AST, ALT > 3 times upper limit of normal)
  • Changes in the ß-blocker, statin or ACE or angiotensin-receptor blocker inhibitor treatment within the past 2 weeks
  • Pregnancy and lactation, inadequate contraception
  • Body weight < 60kg
  • Active bleeding
  • Therapy with CYP3A4 inhibitors (ketoconazole, protease inhibitors, macrolide antibiotics)
  • Therapy with anticoagulants: phenprocoumone, warfarin, dabigatran, rivaroxaban
  • History of hypersensitivity to any of the investigational medicinal products or to any drug with similar chemical structure or to any excipient present in the pharmaceutical form of the investigational medicinal product.
  • Ongoing participation in other clinical trials or within the last 3 months, or ongoing therapy with one of the study medications.
  • Medical or psychological condition that would not permit completion of the trial or signing of informed consent.
  • Patients with acute ST-elevation myocardial infarction

Studieplan

Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.

Hvordan er studiet utformet?

Designdetaljer

  • Primært formål: Grunnvitenskap
  • Tildeling: Randomisert
  • Intervensjonsmodell: Parallell tildeling
  • Masking: Enkelt

Våpen og intervensjoner

Deltakergruppe / Arm
Intervensjon / Behandling
Aktiv komparator: Ticagrelor
Ticagrelor 180mg oral loading dose and 90mg b.i.d for 30 days following coronary artery stenting
All patients will receive a drug eluting stent as clinically indicated.
Ticagrelor 180mg oral loading dose and 90mg b.i.d for 30 days following coronary artery stenting
Aktiv komparator: Clopidogrel
Clopidogrel 600mg loading dose + 75 mg once a day for 30 days following coronary artery stenting.
All patients will receive a drug eluting stent as clinically indicated.
Clopidogrel 600mg loading dose + 75 mg once a day for 30 days following coronary artery stenting.
Aktiv komparator: Prasugrel
Prasugrel 60mg oral loading dose followed by 10mg once a day for 30 days following coronary artery stenting
All patients will receive a drug eluting stent as clinically indicated.
Prasugrel 60mg oral loading dose followed by 10mg once a day for 30 days following coronary artery stenting

Hva måler studien?

Primære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Change in FMD
Tidsramme: baseline and 1 month
The primary endpoint is the change in flow-mediated dilation (FMD) (comparison before treatment versus after treatment and stenting) in the three study groups. The mean FMD across the three measurements (1 day, 1 week, 1 month) performed after coronary artery stenting will be compared to the FMD value before drug administration and stenting.
baseline and 1 month

Sekundære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
FMD 2 hours after loading dose
Tidsramme: baseline and 2 hours after loading dose
Change in FMD 2 hours after the administration of the study drug
baseline and 2 hours after loading dose
L-FMC at 2 hours after the loading dose
Tidsramme: baseline and 2 hours
change in L-FMC at two hours after the loading dose
baseline and 2 hours
L-FMC 1 month after loading dose
Tidsramme: baseline and 1 day after stenting
change in flow-mediated constriction (L-FMC) (comparison before treatment versus after treatment and stenting) in the three study groups. The mean L-FMC across the three measurements (1 day, 1 week, 1 month) performed after coronary artery stenting will be compared to the value before drug administration and stenting
baseline and 1 day after stenting
Safety and tolerability
Tidsramme: from baseline to 1 month after enrollment
Number of patients with adverse events.
from baseline to 1 month after enrollment

Samarbeidspartnere og etterforskere

Det er her du vil finne personer og organisasjoner som er involvert i denne studien.

Etterforskere

  • Studiestol: Thomas Munzel, MD Prof., University Medical Center Mainz

Publikasjoner og nyttige lenker

Den som er ansvarlig for å legge inn informasjon om studien leverer frivillig disse publikasjonene. Disse kan handle om alt relatert til studiet.

Studierekorddatoer

Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.

Studer hoveddatoer

Studiestart

1. august 2012

Primær fullføring (Faktiske)

1. juli 2016

Studiet fullført (Faktiske)

1. september 2016

Datoer for studieregistrering

Først innsendt

4. september 2012

Først innsendt som oppfylte QC-kriteriene

3. oktober 2012

Først lagt ut (Anslag)

4. oktober 2012

Oppdateringer av studieposter

Sist oppdatering lagt ut (Anslag)

7. september 2016

Siste oppdatering sendt inn som oppfylte QC-kriteriene

4. september 2016

Sist bekreftet

1. september 2016

Mer informasjon

Denne informasjonen ble hentet direkte fra nettstedet clinicaltrials.gov uten noen endringer. Hvis du har noen forespørsler om å endre, fjerne eller oppdatere studiedetaljene dine, vennligst kontakt register@clinicaltrials.gov. Så snart en endring er implementert på clinicaltrials.gov, vil denne også bli oppdatert automatisk på nettstedet vårt. .

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