Pharmacodynamic Effect of Prasugrel vs. Ticagrelor in Diabetes

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by University of Florida
Sponsor:
Information provided by (Responsible Party):
University of Florida
ClinicalTrials.gov Identifier:
NCT01852214
First received: May 8, 2013
Last updated: May 28, 2014
Last verified: May 2014

May 8, 2013
May 28, 2014
February 2013
December 2014   (final data collection date for primary outcome measure)
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)
Same as current
Complete list of historical versions of study NCT01852214 on ClinicalTrials.gov Archive Site
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
Same as current
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 randomized to prasugrel will be treated with 60mg loading dose and 10mg maintenance dose
    Other Name: Effient
  • Drug: Ticagrelor
    Patients randomized to ticagrelor will be treated with a 180mg loading dose and 90mg bid maintenance dose
    Other Name: Brillinta
  • Active Comparator: Prasugrel
    prasugrel (60 mg loading dose and 10 mg/daily maintenance dose)
    Interventions:
    • Drug: Prasugrel
    • Drug: Ticagrelor
  • Active Comparator: Ticagrelor
    ticagrelor (180 mg loading dose and 90 mg/B.I.D maintenance dose)
    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.
 
Recruiting
50
January 2015
December 2014   (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
No
Contact: Dominick Angiolillo, MD, PhD 904-244-3933 dominick.angiolillo@jax.ufl.edu
United States
 
NCT01852214
UFJ 2011-184
Yes
University of Florida
University of Florida
Not Provided
Principal Investigator: Dominick Angiolillo, MD, PhD University of Florida
University of Florida
May 2014

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