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Ticagrelor Versus Clopidogrel in Type 2 Diabetic Patients

Primary Purpose

Type-2 Diabetes Mellitus, Coronary Artery Disease

Status

Completed

Phase

Phase 4

Locations

United States

Study Type

Interventional

Intervention

Ticagrelor + Aspirin

Clopidogrel + Aspirin

About this trial

This is an interventional treatment trial for Type-2 Diabetes Mellitus focused on measuring Antiplatelet, Ticagrelor, Clopidogrel, Thrombosis, Diabetes, Coronary Artery Disease

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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).

Sites / Locations

Icahn School of Medicine at Mount Sinai

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Ticagrelor + Aspirin

Clopidogrel + Aspirin

Arm Description

Loading-dose plus daily-dosing for 5-7 days.

Outcomes

Primary Outcome Measures

Thrombus Formation

Thrombus formation in Badimon Perfusion Chamber high-shear) (ex vivo model of thrombosis).

Secondary Outcome Measures

Platelet Reactivity

Platelet reactivity by Multiplate Analyzer

P2Y12 Reaction Unit (PRU)

Platelet reactivity by measuring P2Y12 Reaction Unit using Accumetrics VerifyNow

Platelet Reactivity Index (PRI)

Platelet reactivity index by Vasodilator-Stimulated Phosphoprotein phosphorylation (VASP) assay.

Full Information

NCT ID

NCT01823510

First Posted

March 29, 2013

Last Updated

December 5, 2017

Sponsor

Juan J Badimon

Collaborators

AstraZeneca

1. Study Identification

Unique Protocol Identification Number

NCT01823510

Brief Title

Ticagrelor Versus Clopidogrel in Type 2 Diabetic Patients

Official Title

Comparative Study of the Antithrombotic Effects of Ticagrelor and Clopidogrel in Type 2 Diabetic Patients

Study Type

Interventional

2. Study Status

Record Verification Date

December 2017

Overall Recruitment Status

Completed

Study Start Date

July 2013 (undefined)

Primary Completion Date

May 10, 2016 (Actual)

Study Completion Date

May 10, 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Juan J Badimon

Collaborators

AstraZeneca

4. Oversight

Data Monitoring Committee

5. Study Description

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: 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. Platelet Aggregation - Multiplate Analyzer. Platelet Aggregation - VerifyNow P2Y12 assay. Vasodilator-Stimulated Phosphoprotein (VASP).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Type-2 Diabetes Mellitus, Coronary Artery Disease

Keywords

Antiplatelet, Ticagrelor, Clopidogrel, Thrombosis, Diabetes, Coronary Artery Disease

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Crossover Assignment

Masking

Outcomes Assessor

Allocation

Randomized

Enrollment

20 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Ticagrelor + Aspirin

Arm Type

Experimental

Arm Description

Loading-dose plus daily-dosing for 5-7 days.

Arm Title

Clopidogrel + Aspirin

Arm Type

Active Comparator

Arm Description

Loading-dose plus daily-dosing for 5-7 days.

Intervention Type

Drug

Intervention Name(s)

Ticagrelor + Aspirin

Other Intervention Name(s)

Brilinta (ticagrelor), Aspirin (ASA)

Intervention Description

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).

Intervention Type

Drug

Intervention Name(s)

Clopidogrel + Aspirin

Other Intervention Name(s)

Plavix (clopidogrel), Aspirin (ASA)

Intervention Description

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).

Primary Outcome Measure Information:

Title

Thrombus Formation

Description

Thrombus formation in Badimon Perfusion Chamber high-shear) (ex vivo model of thrombosis).

Time Frame

up to 7 days

Secondary Outcome Measure Information:

Title

Platelet Reactivity

Description

Platelet reactivity by Multiplate Analyzer

Time Frame

up to 7 days

Title

P2Y12 Reaction Unit (PRU)

Description

Platelet reactivity by measuring P2Y12 Reaction Unit using Accumetrics VerifyNow

Time Frame

up to 7 days

Title

Platelet Reactivity Index (PRI)

Description

Platelet reactivity index by Vasodilator-Stimulated Phosphoprotein phosphorylation (VASP) assay.

Time Frame

up to 7 days

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility 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).

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Juan J Badimon, PhD

Organizational Affiliation

Icahn School of Medicine at Mount Sinai

Official's Role

Principal Investigator

Facility Information:

Facility Name

Icahn School of Medicine at Mount Sinai

City

New York

State/Province

New York

ZIP/Postal Code

10029

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

28837213

Citation

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.

Results Reference

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Ticagrelor Versus Clopidogrel in Type 2 Diabetic Patients

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