Now Available: Final Rule for FDAAA 801 and NIH Policy on Clinical Trial Reporting

Pharmacodynamic Effect of Prasugrel vs. Ticagrelor in Diabetes

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
University of Florida
ClinicalTrials.gov Identifier:
NCT01852214
First received: May 8, 2013
Last updated: August 22, 2016
Last verified: June 2016

May 8, 2013
August 22, 2016
February 2013
July 2015   (final data collection date for primary outcome measure)
P2Y12 Reaction Units [ Time Frame: 1 week ] [ Designated as safety issue: No ]
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.
Platelet reactivity [ Time Frame: 1 week ] [ Designated as safety issue: No ]
The primary endpoint is the comparison of the P2Y12 reactivity units (PRU) values determined by VerifyNow between both treatments (ticagrelor or prasugrel)
Complete list of historical versions of study NCT01852214 on ClinicalTrials.gov Archive Site
  • P2Y12 Reaction Units [ Time Frame: 2 hours ] [ Designated as safety issue: No ]
    Comparison of the P2Y12 reaction units (PRU) values determined by VerifyNow between both treatments (ticagrelor or prasugrel)
  • Platelet Reactivity Index [ Time Frame: 1 week ] [ Designated as safety issue: No ]
    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.
  • Platelet Reactivity Index [ Time Frame: 2 hours ] [ Designated as safety issue: No ]
    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.
Markers of platelet reactivity [ Time Frame: 30 min, 2 hours, 24 hours, 1 week ] [ Designated as safety issue: No ]
Markers of platelet reactivity using various platelet function assays
Not Provided
Not Provided
 
Pharmacodynamic Effect of Prasugrel vs. Ticagrelor in Diabetes
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.
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.
Interventional
Not Provided
Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
  • Diabetes Mellitus
  • Coronary Artery Disease
  • Drug: Prasugrel
    Patients receiving prasugrel will be treated with 60mg loading dose and 10mg maintenance dose
    Other Name: Effient
  • Drug: Ticagrelor
    Patients receiving ticagrelor will be treated with a 180mg loading dose and 90mg bid maintenance dose
    Other Name: Brillinta
  • Active Comparator: 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.
    Interventions:
    • Drug: Prasugrel
    • Drug: Ticagrelor
  • Active Comparator: 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.
    Interventions:
    • Drug: Prasugrel
    • Drug: Ticagrelor
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
50
August 2015
July 2015   (final data collection date for primary outcome measure)

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.
Both
18 Years to 74 Years   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01852214
UFJ 2011-184
Yes
No
Not Provided
University of Florida
University of Florida
Not Provided
Principal Investigator: Dominick Angiolillo, MD, PhD University of Florida
University of Florida
June 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP