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Ticagrelor Versus Clopidogrel in Type 2 Diabetic Patients

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ClinicalTrials.gov Identifier: NCT01823510
Recruitment Status : Completed
First Posted : April 4, 2013
Results First Posted : September 1, 2017
Last Update Posted : December 8, 2017
Sponsor:
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
Juan J Badimon, Icahn School of Medicine at Mount Sinai

Tracking Information
First Submitted Date  ICMJE March 29, 2013
First Posted Date  ICMJE April 4, 2013
Results First Submitted Date  ICMJE June 19, 2017
Results First Posted Date  ICMJE September 1, 2017
Last Update Posted Date December 8, 2017
Study Start Date  ICMJE July 2013
Actual Primary Completion Date May 10, 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 2, 2017)
Thrombus Formation [ Time Frame: up to 7 days ]
Thrombus formation in Badimon Perfusion Chamber high-shear) (ex vivo model of thrombosis).
Original Primary Outcome Measures  ICMJE
 (submitted: March 29, 2013)
  • Thrombus Formation [ Time Frame: Baseline (pre-treatment) ]
    Thrombus formation in Badimon Perfusion Chamber (ex vivo model of thrombosis).
  • Thrombus formation [ Time Frame: 2-hour post-loading dose ]
    Thrombus formation in Badimon Perfusion Chamber (ex vivo model of thrombosis).
  • Thrombus formation [ Time Frame: 6-hour post-loading dose ]
    Thrombus formation in Badimon Perfusion Chamber (ex vivo model of thrombosis).
  • Thrombus formation [ Time Frame: after 5-7 days of maintenance dosing ]
    Thrombus formation in Badimon Perfusion Chamber (ex vivo model of thrombosis).
Change History Complete list of historical versions of study NCT01823510 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: August 2, 2017)
  • Platelet Reactivity [ Time Frame: up to 7 days ]
    Platelet reactivity by Multiplate Analyzer
  • P2Y12 Reaction Unit (PRU) [ Time Frame: up to 7 days ]
    Platelet reactivity by measuring P2Y12 Reaction Unit using Accumetrics VerifyNow
  • Platelet Reactivity Index (PRI) [ Time Frame: up to 7 days ]
    Platelet reactivity index by Vasodilator-Stimulated Phosphoprotein phosphorylation (VASP) assay.
Original Secondary Outcome Measures  ICMJE
 (submitted: March 29, 2013)
  • Platelet Reactivity [ Time Frame: Baseline (pre-treatment) ]
    Platelet reactivity by Accumetrics VerifyNow and Multiplate Analyzer.
  • Platelet reactivity [ Time Frame: 2-hour post-loading dose ]
    Platelet reactivity by Accumetrics VerifyNow and Multiplate Analyzer.
  • Platelet reactivity [ Time Frame: 6-hour post-loading dose ]
    Platelet reactivity by Accumetrics VerifyNow and Multiplate Analyzer.
  • Platelet reactivity [ Time Frame: after 5-7 days of maintenance dosing ]
    Platelet reactivity by Accumetrics VerifyNow and Multiplate Analyzer.
  • Vasodilator-Stimulated Phosphoprotein phosphorylation assay [ Time Frame: Baseline (pre-treatment) ]
    Platelet reactivity by Vasodilator-Stimulated Phosphoprotein phosphorylation (VASP) assay.
  • Vasodilator-Stimulated Phosphoprotein phosphorylation assay [ Time Frame: 2-hour post-loading dose ]
    Platelet reactivity by Vasodilator-Stimulated Phosphoprotein phosphorylation (VASP) assay.
  • Vasodilator-Stimulated Phosphoprotein phosphorylation assay [ Time Frame: 6-hour post-loading dose ]
    Platelet reactivity by Vasodilator-Stimulated Phosphoprotein phosphorylation (VASP) assay.
  • Vasodilator-Stimulated Phosphoprotein phosphorylation assay [ Time Frame: after 5-7 days of maintenance dosing. ]
    Platelet reactivity by Vasodilator-Stimulated Phosphoprotein phosphorylation (VASP) assay.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Ticagrelor Versus Clopidogrel in Type 2 Diabetic Patients
Official Title  ICMJE Comparative Study of the Antithrombotic Effects of Ticagrelor and Clopidogrel in Type 2 Diabetic Patients
Brief Summary 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.
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).
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Type-2 Diabetes Mellitus
  • Coronary Artery Disease
Intervention  ICMJE
  • 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)
  • 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)
Study Arms  ICMJE
  • Experimental: Ticagrelor + Aspirin
    Loading-dose plus daily-dosing for 5-7 days.
    Intervention: Drug: Ticagrelor + Aspirin
  • Active Comparator: Clopidogrel + Aspirin
    Loading-dose plus daily-dosing for 5-7 days.
    Intervention: Drug: Clopidogrel + Aspirin
Publications * Zafar MU, Baber U, Smith DA, Sartori S, Contreras J, Rey-Mendoza J, Linares-Koloffon CA, Escolar G, Mehran R, Fuster V, Badimon JJ. Antithrombotic potency of ticagrelor versus clopidogrel in type-2 diabetic patients with cardiovascular disease. Thromb Haemost. 2017 Oct 5;117(10):1981-1988. doi: 10.1160/TH17-04-0277. Epub 2017 Aug 24.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 29, 2013)
20
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE May 10, 2016
Actual Primary Completion Date May 10, 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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).
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01823510
Other Study ID Numbers  ICMJE GCO 13-0208
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Juan J Badimon, Icahn School of Medicine at Mount Sinai
Study Sponsor  ICMJE Juan J Badimon
Collaborators  ICMJE AstraZeneca
Investigators  ICMJE
Principal Investigator: Juan J Badimon, PhD Icahn School of Medicine at Mount Sinai
PRS Account Icahn School of Medicine at Mount Sinai
Verification Date December 2017

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