- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01852214
Pharmacodynamic Effect of Prasugrel vs. Ticagrelor in Diabetes
August 22, 2016 updated by: 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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
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.
Study Type
Interventional
Enrollment (Actual)
50
Phase
- Not Applicable
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
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Florida
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Jacksonville, Florida, United States, 32209
- University of Florida
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 74 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
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.
|
Patients receiving prasugrel will be treated with 60mg loading dose and 10mg maintenance dose
Other Names:
Patients receiving ticagrelor will be treated with a 180mg loading dose and 90mg bid maintenance dose
Other Names:
|
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.
|
Patients receiving prasugrel will be treated with 60mg loading dose and 10mg maintenance dose
Other Names:
Patients receiving ticagrelor will be treated with a 180mg loading dose and 90mg bid maintenance dose
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
1 week
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
P2Y12 Reaction Units
Time Frame: 2 hours
|
Comparison of the P2Y12 reaction units (PRU) values determined by VerifyNow between both treatments (ticagrelor or prasugrel)
|
2 hours
|
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.
|
1 week
|
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.
|
2 hours
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
February 1, 2013
Primary Completion (Actual)
July 1, 2015
Study Completion (Actual)
August 1, 2015
Study Registration Dates
First Submitted
May 8, 2013
First Submitted That Met QC Criteria
May 10, 2013
First Posted (Estimate)
May 13, 2013
Study Record Updates
Last Update Posted (Estimate)
October 17, 2016
Last Update Submitted That Met QC Criteria
August 22, 2016
Last Verified
June 1, 2016
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Heart Diseases
- Cardiovascular Diseases
- Vascular Diseases
- Glucose Metabolism Disorders
- Metabolic Diseases
- Arteriosclerosis
- Arterial Occlusive Diseases
- Endocrine System Diseases
- Coronary Artery Disease
- Myocardial Ischemia
- Coronary Disease
- Diabetes Mellitus
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Platelet Aggregation Inhibitors
- Purinergic P2Y Receptor Antagonists
- Purinergic P2 Receptor Antagonists
- Purinergic Antagonists
- Purinergic Agents
- Ticagrelor
- Prasugrel Hydrochloride
Other Study ID Numbers
- UFJ 2011-184
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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