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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
  Purpose
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.

Condition Intervention
Diabetes Mellitus Coronary Artery Disease Drug: Prasugrel Drug: Ticagrelor

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double Blind (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Pharmacodynamic Comparison of Prasugrel vs. Ticagrelor in Patients With Type 2 Diabetes Mellitus and Coronary Artery Disease

Resource links provided by NLM:


Further study details as provided by University of Florida:

Primary Outcome Measures:
  • P2Y12 Reaction Units [ Time Frame: 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.


Secondary Outcome Measures:
  • P2Y12 Reaction Units [ Time Frame: 2 hours ]
    Comparison of the P2Y12 reaction units (PRU) values determined by VerifyNow between both treatments (ticagrelor or prasugrel)

  • Platelet Reactivity Index [ Time Frame: 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.

  • Platelet Reactivity Index [ Time Frame: 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.


Enrollment: 50
Study Start Date: February 2013
Study Completion Date: August 2015
Primary Completion Date: July 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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: 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.
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

Detailed Description:
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.
  Eligibility

Ages Eligible for Study:   18 Years to 74 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01852214

Locations
United States, Florida
University of Florida
Jacksonville, Florida, United States, 32209
Sponsors and Collaborators
University of Florida
Investigators
Principal Investigator: Dominick Angiolillo, MD, PhD University of Florida
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: University of Florida
ClinicalTrials.gov Identifier: NCT01852214     History of Changes
Other Study ID Numbers: UFJ 2011-184
Study First Received: May 8, 2013
Results First Received: April 15, 2016
Last Updated: August 22, 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by University of Florida:
Diabetes mellitus
Coronary artery disease
prasugrel
ticagrelor

Additional relevant MeSH terms:
Diabetes Mellitus
Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Heart Diseases
Cardiovascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Ticagrelor
Prasugrel Hydrochloride
Purinergic P2Y Receptor Antagonists
Purinergic P2 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Platelet Aggregation Inhibitors

ClinicalTrials.gov processed this record on July 19, 2017