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Pharmacodynamic Effect of Prasugrel vs. Ticagrelor in Diabetes

22. august 2016 opdateret af: University of Florida

A Pharmacodynamic Comparison of Prasugrel vs. Ticagrelor in Patients With Type 2 Diabetes Mellitus and Coronary Artery Disease

Patients with diabetes mellitus (DM) have an increased risk of adverse atherothrombotic events. This may be in part attributed to the fact that these patients have reduced response to oral antiplatelet medications, in particular the P2Y12 receptor inhibitor clopidogrel, used for secondary prevention of ischemic events. Prasugrel and ticagrelor are recently approved P2Y12 receptor inhibitors which, compared with clopidogrel, have more potent antiplatelet effects. Head-to-head comparisons between the two drugs are lacking.

Studieoversigt

Status

Afsluttet

Betingelser

Intervention / Behandling

Detaljeret beskrivelse

Patients with diabetes mellitus (DM) have an increased risk of adverse atherothrombotic events. This may be in part attributed to the fact that these patients have reduced response to oral antiplatelet medications, in particular the P2Y12 receptor inhibitor clopidogrel, used for secondary prevention of ischemic events. Upregulation of platelet P2Y12 receptor mediated signaling has been shown in DM patients and may contribute to these pharmacodynamic observations, suggesting the need for more potent P2Y12 inhibiting strategies in these patients. Prasugrel and ticagrelor are recently approved P2Y12 receptor inhibitors which, compared with clopidogrel, have more potent antiplatelet effects. Therefore, prasugrel and ticagrelor represent attractive treatment options for patients with DM. This is also supported by the DM sub-group analysis of the pivotal TRITON-TIMI 38 (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel-Thrombolysis in Myocardial Infarction) and PLATO (Platelet Inhibition and Patient Outcomes) trials, which have led to approval of prasugrel and ticagrelor, respectively. Although results of these sub-group analysis suggest that prasugrel is associated with an enhanced benefit in DM patients, while ticagrelor effects in DM patients are consistent with the overall study population, only head-to-head comparisons between the two drugs can elucidate if these exert differential effects on platelets from DM patients. However, the pharmacodynamic studies comparing prasugrel with ticagrelor in DM patients are lacking. The ever growing DM population at high risk of recurrent atherothrombotic events underscores the need to define antiplatelet treatment strategies leading to more optimal platelet inhibition in these patients.

Undersøgelsestype

Interventionel

Tilmelding (Faktiske)

50

Fase

  • Ikke anvendelig

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiesteder

  • Forenede Stater
    • Florida
      • Jacksonville, Florida, Forenede Stater, 32209
        • University of Florida

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 with known (angiographically documented) CAD.
  • On maintenance treatment with aspirin (81 mg per day) for at least 1-month as per standard of care.
  • Type 2 DM on treatment with oral hypoglycemic agents and/or insulin.
  • Age between 18 and 74 years old.

Exclusion Criteria:

  • History of stroke, transient ischemic attack or intracranial bleeding.
  • On treatment with a P2Y12 receptor antagonist (ticlopidine, clopidogrel, prasugrel, ticagrelor).
  • Known allergies to aspirin, ticlopidine, clopidogrel, prasugrel, ticagrelor.
  • Weight <60kg.
  • On treatment with oral anticoagulant (Vitamin K antagonists, dabigatran).
  • Blood dyscrasia or bleeding diathesis.
  • Platelet count <80x106/mL.
  • Hemoglobin <10 g/dL.
  • Active bleeding or hemodynamic instability.
  • Creatinine Clearance <30 mL/minute.
  • Baseline ALT >2.5 times the upper limit of normal.
  • Hb A1c ≥ 10 mg/dL within 3 months.
  • Patients with sick sinus syndrome (SSS) or high degree AV block without pacemaker protection.
  • Drugs interfering 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: Crossover opgave
  • Maskning: Dobbelt

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Aktiv komparator: Prasugrel first, then ticagrelor
Patients randomized to prasugrel will receive prasugrel loading dose followed by maintenance dose. Randomized treatment will be maintained for 1-week (7±2 days). After completion of the 1-week treatment period, patients will discontinued the study medications for 2-4 weeks (wash-out period) and then will cross over to the alternate treatment (ticagrelor), which will be administered for 1-week.
Medicin: Prasugrel
Patients receiving prasugrel will be treated with 60mg loading dose and 10mg maintenance dose
Andre navne:
  • Effektiv
Medicin: Ticagrelor
Patients receiving ticagrelor will be treated with a 180mg loading dose and 90mg bid maintenance dose
Andre navne:
  • Brillinta
Aktiv komparator: Ticagrelor first, then prasugrel
Patients randomized to ticagrelor will receive prasugrel loading dose followed by maintenance dose. Randomized treatment will be maintained for 1-week (7±2 days). After completion of the 1-week treatment period, patients will discontinued the study medications for 2-4 weeks (wash-out period) and then will cross over to the alternate treatment (prasugrel), which will be administered for 1-week.
Medicin: Prasugrel
Patients receiving prasugrel will be treated with 60mg loading dose and 10mg maintenance dose
Andre navne:
  • Effektiv
Medicin: Ticagrelor
Patients receiving ticagrelor will be treated with a 180mg loading dose and 90mg bid maintenance dose
Andre navne:
  • Brillinta

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
P2Y12 Reaction Units
Tidsramme: 1 week
The primary endpoint is the comparison of the P2Y12 reaction units (PRU) values determined by VerifyNow between both treatments (ticagrelor or prasugrel). Treatment effects were evaluated comparing PRU observed in the overall patient population after prasugrel treatment with those achieved after ticagrelor regardless of the sequence.
1 week

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
P2Y12 Reaction Units
Tidsramme: 2 hours
Comparison of the P2Y12 reaction units (PRU) values determined by VerifyNow between both treatments (ticagrelor or prasugrel)
2 hours
Platelet Reactivity Index
Tidsramme: 1 week
The comparison of the platelet reactivity index (PRI) values determined by vasodilator-stimulated phosphoprotein (VASP) between both treatments (ticagrelor or prasugrel). VASP was measured by quantitative flow cytometry using commercially available labelled monoclonal antibodies. A low PRI is indicative of high platelet inhibition.
1 week
Platelet Reactivity Index
Tidsramme: 2 hours
The comparison of the platelet reactivity index (PRI) values determined by vasodilator-stimulated phosphoprotein (VASP) between both treatments (ticagrelor or prasugrel). VASP was measured by quantitative flow cytometry using commercially available labelled monoclonal antibodies. A low PRI is indicative of high platelet inhibition.
2 hours

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Sponsor

University of Florida

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.

Generelle publikationer

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. februar 2013

Primær færdiggørelse (Faktiske)

1. juli 2015

Studieafslutning (Faktiske)

1. august 2015

Datoer for studieregistrering

Først indsendt

8. maj 2013

Først indsendt, der opfyldte QC-kriterier

10. maj 2013

Først opslået (Skøn)

13. maj 2013

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Skøn)

17. oktober 2016

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

22. august 2016

Sidst verificeret

1. juni 2016

Mere information

Begreber relateret til denne undersøgelse

Nøgleord

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

  • UFJ 2011-184

Plan for individuelle deltagerdata (IPD)

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INGEN

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