- ICH GCP
- US Clinical Trials Registry
- Klinisk forsøg NCT02065479
A Pharmacodynamic Study Comparing Prasugrel Versus Ticagrelor in Patients Undergoing PCI With CYP2C19 Loss-of-function:
27. august 2020 opdateret af: University of Florida
A Pharmacodynamic Study Comparing Prasugrel Versus Ticagrelor in Patients With Coronary Artery Disease Undergoing PCI With CYP2C19 Loss-of-function Genotypes: A Feasibility Study With Point-of-care Pharmacodynamic and Genetic Testing
Numerous studies have shown that pharmacodynamics (PD) response profiles vary among clopidogrel treated patients and that individuals with reduced response have an increased risk of recurrent ischemic events.
There are multiple factors contributing to clopidogrel response variability, including genetic variations of the cytochrome P450 (CYP) 2C19 enzyme.
In particular, loss-of-function (LOF) alleles of the CYP2C19 enzyme reduce transformation of clopidogrel pro-drug into its active metabolite.
Thus, patients carrying LOF alleles have lower levels of clopidogrel's active metabolite as well as diminished platelet inhibition, which translates into an increased rate of adverse cardiovascular events, particularly in the setting of percutaneous coronary intervention (PCI).
Prasugrel and ticagrelor are novel generation P2Y12 receptor inhibitors characterized by greater PD potency and reduced ischemic event rates compared with clopidogrel, and are not affected by CYP2C19 LOF polymorphisms.
However, to date there are limited head-to-head PD comparisons between these two new P2Y12 receptors blockers, and there are no studies assessing on how these agents behave among CYP2C19 LOF carriers.
The aim of the present study is to compare the PD effects of prasugrel versus ticagrelor in patients undergoing PCI with CYP2C19 LOF alleles using the novel point-of-care genetic testing Spartan RX-CYP2C19 which permits accurate and rapid identification of CYP2C19 genetic status.
Studieoversigt
Status
Afsluttet
Betingelser
Intervention / Behandling
Detaljeret beskrivelse
Clopidogrel is the most broadly utilized platelet P2Y12 receptor inhibitor.
However, numerous studies have shown that pharmacodynamics (PD) response profiles vary among clopidogrel treated patients and that individuals with reduced response have an increased risk of recurrent ischemic events.
There are multiple factors contributing to clopidogrel response variability.
Among these, genetic variations of the cytochrome P450 (CYP) 2C19 enzyme, a key contributor to clopidogrel metabolism, have been involved.
In particular, loss-of-function (LOF) alleles of the CYP2C19 enzyme reduce transformation of clopidogrel pro-drug into its active metabolite.
Thus, patients carrying LOF alleles have lower levels of clopidogrel's active metabolite as well as diminished platelet inhibition, which translates into an increased rate of adverse cardiovascular events, particularly in the setting of percutaneous coronary intervention (PCI).
Because of these findings, drug regulating authorities have provided a boxed warning on the product label of clopidogrel on the potential for reduced efficacy of clopidogrel among CYP2C19 LOF carriers and suggested considering alternative antiplatelet therapies for these individuals.
Prasugrel and ticagrelor are novel generation P2Y12 receptor inhibitors characterized by greater PD potency and reduced ischemic event rates compared with clopidogrel, and are not affected by CYP2C19 LOF polymorphisms.
However, to date there are limited head-to-head PD comparisons between these two new P2Y12 receptors blockers, and there are no studies assessing on how these agents behave among CYP2C19 LOF carriers.
Tailoring antiplatelet therapy according to results of genetic testing has been limited in real world clinical practice because of not having readily accessible results of individual's genetic makeup.
The aim of the present study is to compare the PD effects of prasugrel versus ticagrelor in patients undergoing PCI with CYP2C19 LOF alleles using the novel point-of-care genetic testing Spartan RX-CYP2C19 which permits accurate and rapid identification of CYP2C19 genetic status.
Undersøgelsestype
Interventionel
Tilmelding (Faktiske)
65
Fase
- Fase 4
Kontakter og lokationer
Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.
Studiesteder
-
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Florida
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Jacksonville, Florida, Forenede Stater, 32209
- University of Florida
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Deltagelseskriterier
Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.
Berettigelseskriterier
Aldre berettiget til at studere
18 år til 74 år (Voksen, Ældre voksen)
Tager imod sunde frivillige
Ingen
Køn, der er berettiget til at studere
Alle
Beskrivelse
Inclusion criteria:
- Patients scheduled for left heart catheterization and undergoing PCI
- Age 18-75 years
- On aspirin (81mg) or aspirin (81mg) and clopidogrel (75mg/day)
- Presence of at least one 2C19 LOF allele
Exclusion criteria:
- Known allergies to aspirin, prasugrel, ticagrelor, or clopidogrel
- Age >75 years
- Weight <60kg
- Considered at high risk for bleeding
- History of ischemic or hemorrhagic stroke or transient ischemic attack
- Known severe hepatic dysfunction
- On treatment with oral anticoagulant therapy (Vitamin K antagonists, dabigatran, apixaban, rivaroxaban)
- Use of glycoprotein IIb/IIIa inhibitors (abciximab, eptifibatide, tirofiban)
- Blood dyscrasia or bleeding diathesis
- Platelet count <80x106/mL
- Hemoglobin <10 g/dL.
- Active bleeding or hemodynamic instability
- Creatinine Clearance <30 mL/minute
- Patients with sick sinus syndrome (SSS) or high degree AV block without pacemaker protection.
- Current treatment with drugs interfering with CYP3A4 metabolism (to avoid interaction with Ticagrelor): Ketoconazole, itraconazole, voriconazole, clarithromycin, nefazodone, ritonavir, saquinavir, nelfinavir, indinavir, atazanavir, and telithromizycin.
- Pregnant females* *Women of childbearing age must use reliable birth control (i.e. oral contraceptives) while participating in the study.
Studieplan
Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: Randomiseret
- Interventionel model: Parallel tildeling
- Maskning: Ingen (Åben etiket)
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
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Aktiv komparator: Ticagrelor
The primary endpoint is the non-inferiority in platelet reactivity of prasugrel versus ticagrelor among CYP2C19 loss of function allele carriers.
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Comparison of platelet reactivity between prasugrel and ticagrelor
Andre navne:
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Eksperimentel: Prasugrel
The primary endpoint is the non-inferiority in platelet reactivity of prasugrel versus ticagrelor among CYP2C19 loss of function allele carriers.
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Comparison of platelet reactivity between prasugrel and ticagrelor
Andre navne:
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Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
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Platelet Reactivity
Tidsramme: 24 hours post loading dose
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The primary endpoint is P2Y12 reaction unit (PRU) measured by the Verify Now P2Y12 assay 24hours/hospital discharge post randomization to prasugrel vs ticagrelor.
PRU is is an arbitrary unit of measure to assess ADP-induced platelet aggregation.
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24 hours post loading dose
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Samarbejdspartnere og efterforskere
Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.
Sponsor
Publikationer og nyttige links
Den person, der er ansvarlig for at indtaste oplysninger om undersøgelsen, leverer frivilligt disse publikationer. Disse kan handle om alt relateret til undersøgelsen.
Datoer for undersøgelser
Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.
Studer store datoer
Studiestart
1. marts 2014
Primær færdiggørelse (Faktiske)
22. april 2019
Studieafslutning (Faktiske)
22. april 2019
Datoer for studieregistrering
Først indsendt
12. februar 2014
Først indsendt, der opfyldte QC-kriterier
14. februar 2014
Først opslået (Skøn)
19. februar 2014
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
16. september 2020
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
27. august 2020
Sidst verificeret
1. august 2020
Mere information
Begreber relateret til denne undersøgelse
Yderligere relevante MeSH-vilkår
- Hjertesygdomme
- Hjerte-kar-sygdomme
- Karsygdomme
- Åreforkalkning
- Arterielle okklusive sygdomme
- Koronararteriesygdom
- Myokardieiskæmi
- Koronar sygdom
- Lægemidlers fysiologiske virkninger
- Neurotransmittermidler
- Molekylære mekanismer for farmakologisk virkning
- Blodpladeaggregationshæmmere
- Purinerge P2Y-receptorantagonister
- Purinerge P2-receptorantagonister
- Purinerge antagonister
- Purinerge midler
- Ticagrelor
- Prasugrel Hydrochlorid
Andre undersøgelses-id-numre
- UFJ 2014-12
- IRB201702750 (Anden identifikator: UF IRB)
Plan for individuelle deltagerdata (IPD)
Planlægger du at dele individuelle deltagerdata (IPD)?
Ingen
Lægemiddel- og udstyrsoplysninger, undersøgelsesdokumenter
Studerer et amerikansk FDA-reguleret lægemiddelprodukt
Ingen
Studerer et amerikansk FDA-reguleret enhedsprodukt
Ingen
produkt fremstillet i og eksporteret fra U.S.A.
Ingen
Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .
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University of MilanAfsluttet
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University of PatrasAfsluttet
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Medstar Health Research InstituteAfsluttetAkut koronarsyndromForenede Stater
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University of FloridaAfsluttetKoronararteriesygdomForenede Stater
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VA Office of Research and DevelopmentAfsluttetKoronararterie bypassForenede Stater
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Eli Lilly and CompanyAfsluttet
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Daiichi Sankyo Taiwan Ltd., a Daiichi Sankyo CompanyAfsluttetAkut koronarsyndrom (ACS)Taiwan