Ticagrelor With and Without Aspirin in Patients With Diabetes Mellitus

NCT04484259 | Completed Phase 4 Results DMC FDA Drug

• 1 other identifier: IRB202001694
• Study Type: interventional
• Target: 105
• Locations: 1 country
• Sites: 1

Brief Summary

Recent studies have shown that withdrawing aspirin and maintaining P2Y12 inhibitor monotherapy for up to 12 months post-PCI, after a brief period of DAPT, reduces bleeding without increasing ischemic harm. Such effects have shown to of particular benefit in patients with diabetes mellitus (DM). However, if an aspirin-free approach can be considered after this time frame is a matter of debate. The aim of this study is to assess the PD effects of ticagrelor 60 mg with and without aspirin therapy in CAD patients and to compare this with a standard DAPT regimen of aspirin plus clopidogrel.

Conditions

Diabetes Mellitus, Type 2; Coronary Artery Disease

Keywords

diabetes mellitus; ticagrelor; clopidogrel; percutaneous coronary intervention

Outcome Measures

Primary Outcomes (1)

• P2Y12 Reaction Units (PRU)

  The primary end-point of the study is the comparison of the PRU determined by VerifyNow PRU between between aspirin plus ticagrelor 60 mg and ticagrelor 60 mg monotherapy (trough effect pre-dosing). The VerifyNow System is a turbidimetric based optical detection system which measures platelet induced aggregation as an increase in light transmittance. The assay is based on microbead agglutination induced by adenosine diphosphate (ADP). The instrument measures this change in optical signal and reports results in P2Y12 Reaction Units (PRU).

  Day 10, pre-dose

Other Outcomes (3)

• VASP

  Day 10, pre-dose

• Comparison of Platelet Aggregation With ADP as Stimuli Determined by Light Transmittance Aggregometry Between Between Aspirin Plus Ticagrelor 60 mg and Ticagrelor 60 mg Monotherapy.

  Day 10, pre-dose

• Comparison of Thrombus Formation Measured by T-TAS Between Between Aspirin Plus Ticagrelor 60 mg and Ticagrelor 60 mg Monotherapy

  Day 10, pre-dose

Study Arms (3)

Ticagrelor

EXPERIMENTAL

ticagrelor 60 mg bid monotherapy

Drug: Ticagrelor monotherapy

Aspirin plus Clopidogrel

ACTIVE COMPARATOR

aspirin 81 mg qd plus clopidogrel 75 mg qd

Drug: Clopidogrel with aspirin

Aspirin plus Ticagrelor

ACTIVE COMPARATOR

aspirin 81 mg qd plus ticagrelor 60 mg bid

Drug: Ticagrelor plus aspirin

Interventions

Ticagrelor monotherapy DRUG

Eligible patients will enter a 7-10 day run-in phase with aspirin 81 mg/ qd plus ticagrelor 90 mg bid after which they will discontinue aspirin and maintain ticagrelor 90 mg bid monotherapy for 10±3 days. After this period, patients will be randomized using a randomly generated computer sequence in a 1:1:1 fashion to either: a) ticagrelor 60 mg bid monotherapy; b) aspirin 81 mg qd plus ticagrelor 60 mg bid; c) aspirin 81 mg qd plus clopidogrel 75 mg qd. Randomized treatment will be maintained for 10±3 days.

Also known as: Brilinta

Ticagrelor

Ticagrelor plus aspirin DRUG

Eligible patients will enter a 7-10 day run-in phase with aspirin 81 mg/ qd plus ticagrelor 90 mg bid after which they will discontinue aspirin and maintain ticagrelor 90 mg bid monotherapy for 10±3 days. After this period, patients will be randomized using a randomly generated computer sequence in a 1:1:1 fashion to either: a) ticagrelor 60 mg bid monotherapy; b) aspirin 81 mg qd plus ticagrelor 60 mg bid; c) aspirin 81 mg qd plus clopidogrel 75 mg qd. Randomized treatment will be maintained for 10±3 days.

Also known as: Brilinta

Aspirin plus Ticagrelor

Clopidogrel with aspirin DRUG

Eligible patients will enter a 7-10 day run-in phase with aspirin 81 mg/ qd plus ticagrelor 90 mg bid after which they will discontinue aspirin and maintain ticagrelor 90 mg bid monotherapy for 10±3 days. After this period, patients will be randomized using a randomly generated computer sequence in a 1:1:1 fashion to either: a) ticagrelor 60 mg bid monotherapy; b) aspirin 81 mg qd plus ticagrelor 60 mg bid; c) aspirin 81 mg qd plus clopidogrel 75 mg qd. Randomized treatment will be maintained for 10±3 days.

Also known as: Plavix

Aspirin plus Clopidogrel

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of informed consent prior to any study specific procedures
• Men or women ≥18 years of age
• Diagnosed with type 2 DM defined by ongoing glucose lowering therapy (oral medications and/or insulin) treatment for at least 1 month
• Known angiographically defined CAD (including a history of previous PCI, CABG, or \>50% stenosis in a major epicardial vessel) on standard of care antiplatelet therapy\* \*Patients can be treated with any background antiplatelet treatment regimen as part of their standard of care, including aspirin and/or any P2Y12 inhibitor (clopidogrel, ticagrelor, prasugrel).

You may not qualify if:

• PCI \< 6 months prior
• Recent (\< 6 months) type I myocardial infarction
• Anticipated concomitant oral or intravenous therapy with strong cytochrome P450 3A4 (CYP3A4) inhibitors or CYP3A4 substrates with narrow therapeutic indices that cannot be stopped for the course of the study:
• Strong inhibitors: ketoconazole, itraconazole, voriconazole, telithromycin, clarithromycin (but not erythromycin or azithromycin), nefazadone, ritonavir, saquinavir, nelfinavir, indinavir, atanazavir
• CYP3A4 substrates with narrow therapeutic index: quinidine, simvastatin at doses \>40 mg daily or lovastatin at doses \>40 mg daily
• Anticipated concomitant oral or intravenous therapry of strong CYP3A inducers (phenytoin, rifampin, phenobarb, carbamazepine)
• Need for chronic oral anticoagulant therapy or chronic low-molecular-weight heparin (at venous thrombosis treatment not prophylaxis doses)
• Patients with known bleeding diathesis or coagulation disorder
• History of previous intracerebral bleed at any time, gastrointestinal (GI) bleed within the past 6 months prior to randomization, or major surgery within 30 days prior to randomization
• Active pathological bleeding
• Hypersensitivity to aspirin, ticagrelor or clopidogrel
• Increased risk of bradycardic events (eg, known sick sinus syndrome, second or third degree AV block or previous documented syncope suspected to be due to bradycardia) unless treated with a pacemaker
• Known severe liver disease
• Renal failure requiring dialysis
• Known platelet count \<80x106/mL

Sponsors & Collaborators

• University of Florida: lead
• AstraZeneca: collaborator

Study Sites (1)

University of Florida

Jacksonville, Florida, 32209, United States

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Coronary Artery Disease; Diabetes Mellitus

Interventions

Ticagrelor; Aspirin; Clopidogrel

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases

Intervention Hierarchy (Ancestors)

Adenosine; Purine Nucleosides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Ticlopidine; Thienopyridines; Thiophenes; Sulfur Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Results Point of Contact

• Title: Francesco Franchi, MD
• Organization: University of Florida College of Medicine Jacksonville

francesco.franchi@jax.ufl.edu

904-244-5515

Study Officials

• Dominick J Angiolillo, MD,PhD

  University of Florida

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Staff performing PK/PD assessments will remain blinded to treatment assignment.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Prospective randomized

Study Record Dates

• First Submitted: July 21, 2020
• First Posted: July 23, 2020
• Study Start: March 31, 2021
• Primary Completion: January 29, 2024
• Study Completion: June 15, 2024
• Last Updated: March 30, 2025
• Results First Posted: March 30, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)