Ticagrelor Versus Clopidogrel in Type 2 Diabetic Patients

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2014 by Mount Sinai School of Medicine
Sponsor:
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
Juan J Badimon, Mount Sinai School of Medicine
ClinicalTrials.gov Identifier:
NCT01823510
First received: March 29, 2013
Last updated: January 16, 2014
Last verified: January 2014
  Purpose

The purpose of this study is to determine whether treatment with ticagrelor + aspirin is more effective than treatment with clopidogrel + aspirin in patients with type-2 diabetes. Both treatments will be given (separately) to all subjects as a one-time loading dose (i.e. higher than a normal daily dose), followed by daily dose for the next 5 to 7 days. Effectiveness of treatment will be measured with specialized blood tests before the loading dose, at two time-points after the loading dose, and once after the last daily dose.


Condition Intervention Phase
Type-2 Diabetes Mellitus
Coronary Artery Disease
Drug: Ticagrelor + Aspirin
Drug: Clopidogrel + Aspirin
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Crossover Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Comparative Study of the Antithrombotic Effects of Ticagrelor and Clopidogrel in Type 2 Diabetic Patients

Resource links provided by NLM:


Further study details as provided by Mount Sinai School of Medicine:

Primary Outcome Measures:
  • Thrombus formation [ Time Frame: Baseline (pre-treatment) ] [ Designated as safety issue: No ]
    Thrombus formation in Badimon Perfusion Chamber (ex vivo model of thrombosis).

  • Thrombus formation [ Time Frame: 2-hour post-loading dose ] [ Designated as safety issue: No ]
    Thrombus formation in Badimon Perfusion Chamber (ex vivo model of thrombosis).

  • Thrombus formation [ Time Frame: 6-hour post-loading dose ] [ Designated as safety issue: No ]
    Thrombus formation in Badimon Perfusion Chamber (ex vivo model of thrombosis).

  • Thrombus formation [ Time Frame: after 5-7 days of maintenance dosing ] [ Designated as safety issue: No ]
    Thrombus formation in Badimon Perfusion Chamber (ex vivo model of thrombosis).


Secondary Outcome Measures:
  • Platelet reactivity [ Time Frame: Baseline (pre-treatment) ] [ Designated as safety issue: No ]
    Platelet reactivity by Accumetrics VerifyNow and Multiplate Analyzer.

  • Platelet reactivity [ Time Frame: 2-hour post-loading dose ] [ Designated as safety issue: No ]
    Platelet reactivity by Accumetrics VerifyNow and Multiplate Analyzer.

  • Platelet reactivity [ Time Frame: 6-hour post-loading dose ] [ Designated as safety issue: No ]
    Platelet reactivity by Accumetrics VerifyNow and Multiplate Analyzer.

  • Platelet reactivity [ Time Frame: after 5-7 days of maintenance dosing ] [ Designated as safety issue: No ]
    Platelet reactivity by Accumetrics VerifyNow and Multiplate Analyzer.

  • Vasodilator-Stimulated Phosphoprotein phosphorylation assay [ Time Frame: Baseline (pre-treatment) ] [ Designated as safety issue: No ]
    Platelet reactivity by Vasodilator-Stimulated Phosphoprotein phosphorylation (VASP) assay.

  • Vasodilator-Stimulated Phosphoprotein phosphorylation assay [ Time Frame: 2-hour post-loading dose ] [ Designated as safety issue: No ]
    Platelet reactivity by Vasodilator-Stimulated Phosphoprotein phosphorylation (VASP) assay.

  • Vasodilator-Stimulated Phosphoprotein phosphorylation assay [ Time Frame: 6-hour post-loading dose ] [ Designated as safety issue: No ]
    Platelet reactivity by Vasodilator-Stimulated Phosphoprotein phosphorylation (VASP) assay.

  • Vasodilator-Stimulated Phosphoprotein phosphorylation assay [ Time Frame: after 5-7 days of maintenance dosing. ] [ Designated as safety issue: No ]
    Platelet reactivity by Vasodilator-Stimulated Phosphoprotein phosphorylation (VASP) assay.


Estimated Enrollment: 20
Study Start Date: July 2013
Estimated Study Completion Date: May 2015
Estimated Primary Completion Date: May 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ticagrelor + Aspirin
Single loading doses of Ticagrelor (180 mg) and ASA (325 mg), followed by daily dosing for 5-7 days (ticagrelor 90 mg twice daily + ASA 81 mg once daily).
Drug: Ticagrelor + Aspirin
Single loading doses of Ticagrelor (180 mg) and ASA (325 mg), followed by daily dosing for 5-7 days (ticagrelor 90 mg twice daily + ASA 81 mg once daily).
Other Names:
  • Brilinta (ticagrelor)
  • Aspirin (ASA)
Active Comparator: Clopidogrel + Aspirin
Single loading doses of Clopidogrel (600 mg) and ASA (325 mg), followed by daily dosing for 5-7 days (clopidogrel 75 mg + ASA 81 mg once daily).
Drug: Clopidogrel + Aspirin
Single loading doses of Clopidogrel (600 mg) and ASA (325 mg), followed by daily dosing for 5-7 days (clopidogrel 75 mg + ASA 81 mg once daily).
Other Names:
  • Plavix (clopidogrel)
  • Aspirin (ASA)

Detailed Description:

The rising prevalence of diabetes mellitus and its associated cardiovascular complications present a major burden to healthcare providers worldwide. Cardiovascular mortality is much higher among subjects with Type 2 Diabetes Mellitus (T2DM). Increased platelet reactivity is considered a potential link between the two diseases. Thus, given the higher blood thrombogenicity of T2DM with CAD, the availability of more potent antiplatelet drugs should be associated with improvements in the prevention of cardiovascular events in the diabetic populations. Ticagrelor has been shown to possess a faster onset of action and more potency than clopidogrel. Furthermore, the PLATO has shown that these characteristics results in a significant reduction in Cardiovascular events and even death as compared with Clopidogrel.

We plan to compare the antithrombotic activity of ticagrelor versus clopidogrel in T2DM patients using a cross-over study design. Each participant will be randomly assigned to receive ticagrelor/clopidogrel + aspirin as a loading dose followed by 5-7 days of daily maintenance dosing. After a washout period of 1-2 weeks, each participant will receive the second treatment (clopidogrel/ticagrelor + aspirin) again as a loading dose followed by 5-7 days of daily dosing. Platelet function will be tested at pre-treatment baseline, two post-dose time-points on the day of loading dose, and one time-point after the last maintenance dose on day 5-7. Platelet testing will be carried out using the following methodologies:

  1. Badimon Perfusion Chamber: an ex-vivo model of thrombosis that has been extensively utilized for evaluation of antithrombotic or prothrombotic effects under various pathological states. The model involves native blood perfusing over a thrombogenic substrate, triggering thrombus formation that can be measured by planimetry.
  2. Platelet Aggregation - Multiplate Analyzer.
  3. Platelet Aggregation - VerifyNow P2Y12 assay.
  4. Vasodilator-Stimulated Phosphoprotein (VASP).
  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosed with type-2 diabetes being treated with oral or parenteral hypoglycemic therapy or both.
  • Have not had thienopyridine therapy for at least 30 days before the study.
  • Are of legal age (at least 18 years of age but less than 75 years of age) and competent mental condition to provide written informed consent.
  • For women of child-bearing potential only test negative for pregnancy at the time of enrollment.

Exclusion Criteria:

  • Have a defined need for thienopyridine therapy.
  • Subjects within ≤30 days of coronary artery bypass graft (CABG) surgery or percutaneous coronary intervention (PCI).
  • Known glycosylated hemoglobin (HbA1c) ≥10 mg/dL within last 3 months prior to study entry.
  • Have received fibrinolytic therapy <48 hours prior to randomization.
  • Have active internal bleeding or history of bleeding diathesis.
  • Have clinical findings that are, in the judgment of the investigator, associated with an increased risk of bleeding.
  • Have history of ischemic or hemorrhagic stroke, transient ischemic attack (TIA) or intracranial neoplasm, arteriovenous malformation, or aneurysm.
  • Have an International Normalized Ratio (INR) known to be >1.5 within 1 week of study entry.
  • Have a known platelet count of <100,000/mm3 within 1 week of study entry.
  • Have known anemia (hemoglobin [Hgb] <10 gm/dL) within 1 week of study entry.
  • Are receiving or will receive oral anticoagulation or other antiplatelet therapy (other than ASA) that cannot be safely discontinued for the duration of the trial.
  • Are receiving daily treatment with non-steroidal anti-inflammatory drugs (NSAIDS) that cannot be discontinued.
  • Have a concomitant medical illness that in the opinion of the investigator may interfere with or prevent completion in this study.
  • Have known severe hepatic dysfunction (e.g., cirrhosis or portal hypertension).
  • Have a history of intolerance or allergy to ASA or approved thienopyridines (ticlopidine or clopidogrel).
  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: NCT01823510

Contacts
Contact: Juan J Badimon, PhD (212) 241-8484 Juan.Badimon@mssm.edu
Contact: M. Urooj Zafar, MBBS (212) 241-8484 Urooj.Zafar@mssm.edu

Locations
United States, New York
Icahn School of Medicine at Mount Sinai Recruiting
New York, New York, United States, 10029
Principal Investigator: Juan J Badimon, PhD         
Sponsors and Collaborators
Juan J Badimon
AstraZeneca
Investigators
Principal Investigator: Juan J Badimon, PhD Mount Sinai School of Medicine
  More Information

No publications provided

Responsible Party: Juan J Badimon, Professor, Mount Sinai School of Medicine
ClinicalTrials.gov Identifier: NCT01823510     History of Changes
Other Study ID Numbers: GCO 13-0208
Study First Received: March 29, 2013
Last Updated: January 16, 2014
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Keywords provided by Mount Sinai School of Medicine:
Antiplatelet
Ticagrelor
Clopidogrel
Thrombosis
Diabetes
Coronary Artery Disease

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
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
Aspirin
Ticlopidine
Clopidogrel
Ticagrelor
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 18, 2014