- ICH GCP
- US Clinical Trials Registry
- Klinisk utprøving NCT01700322
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
Status
Fullført
Forhold
Intervensjon / Behandling
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.
Generelle publikasjoner
- Schnorbus B, Jurk K, Lackner KJ, Welk C, Munzel T, Gori T. Effects of Clopidogrel, Prasugrel and Ticagrelor on Microvascular Function and Platelet Reactivity in Patients With Acute Coronary Syndrome Undergoing Coronary Artery Stenting. A Randomized, Blinded, Parallel Group Trial. Front Cardiovasc Med. 2021 Dec 13;8:780605. doi: 10.3389/fcvm.2021.780605. eCollection 2021.
- Schnorbus B, Daiber A, Jurk K, Warnke S, Konig J, Krahn U, Lackner K, Munzel T, Gori T. Effects of clopidogrel, prasugrel and ticagrelor on endothelial function, inflammatory and oxidative stress parameters and platelet function in patients undergoing coronary artery stenting for an acute coronary syndrome. A randomised, prospective, controlled study. BMJ Open. 2014 May 6;4(5):e005268. doi: 10.1136/bmjopen-2014-005268.
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
Begreper knyttet til denne studien
Ytterligere relevante MeSH-vilkår
- Hjertesykdommer
- Kardiovaskulære sykdommer
- Vaskulære sykdommer
- Arteriosklerose
- Arterielle okklusive sykdommer
- Koronararteriesykdom
- Myokardiskemi
- Koronar sykdom
- Fysiologiske effekter av legemidler
- Nevrotransmittere agenter
- Molekylære mekanismer for farmakologisk virkning
- Blodplateaggregasjonshemmere
- Purinergiske P2Y-reseptorantagonister
- Purinergiske P2-reseptorantagonister
- Purinergiske antagonister
- Purinergiske midler
- Ticagrelor
- Klopidogrel
- Prasugrel hydroklorid
Andre studie-ID-numre
- CTH-C1
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. .
Kliniske studier på Koronararteriesykdom
-
IRCCS Policlinico S. DonatoRekrutteringAnomalous aortic origin of the coronary artery (AAOCA)Italia
-
Medtronic CardiovascularFullførtArteriosclerosis of coronary artery bypass graftCanada, Forente stater
-
Lawson Health Research InstituteFullførtArteriosclerosis of arterial coronary artery bypass graftCanada
-
Deutsches Herzzentrum MuenchenFullførtArteriosclerosis of arterial coronary artery bypass graftTyskland
-
William Beaumont HospitalsFullførtKoronararteriesykdom | Arteriosclerosis of coronary artery bypass graftForente stater
-
Izmir Bakircay UniversityFullførtMyocardial Bridge of Coronary ArteryTyrkia
-
ITAB - Institute for Advanced Biomedical TechnologiesAzienda Ospedaliero, Universitaria Ospedali RiunitiFullførtMyocardial Bridge of Coronary ArteryItalia
-
University Hospital OstravaRekrutteringIn-Stent Carotis Artery RestenosisTsjekkia
-
Zhejiang Cancer HospitalRekrutteringHepatic Artery Infusion | Levermetastase fra brystkreftKina
-
Stanford UniversityAmerican Heart AssociationRekrutteringAngina pectoris | Mikrovaskulær angina | Vasospastisk angina | Myocardial Bridge of Coronary ArteryForente stater
Kliniske studier på Coronary stenting
-
Elixir Medical CorporationFullført
-
Yonsei UniversityUkjentKolangiokarsinom, galleblærekreft, bukspyttkjertelkreftKorea, Republikken
-
Biotronik AGFullførtKoronararteriesykdomRomania
-
Istanbul UniversityFullført
-
University of MichiganFullførtKoronararteriesykdom | PsoriasisForente stater
-
Conor MedsystemsAvsluttet
-
Catharina Ziekenhuis EindhovenAvsluttet
-
Shockwave Medical, Inc.Fullført
-
Seoul National University HospitalSamsung Medical Center, Sungkyunkwan University School of Medicine; Ulsan... og andre samarbeidspartnereAktiv, ikke rekrutterendeStabil anginaKorea, Republikken, Kina
-
Istanbul Mehmet Akif Ersoy Educational and Training...FullførtKoronararteriesykdomTyrkia