Low Maintenance Dose Ticagrelor Versus Clopidogrel in Diabetes Patients Undergoing PCI

NCT03437044 | Completed Phase 4 Results DMC FDA Drug

• 1 other identifier: ESR 13396
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

To date there is very little PD and pharmacokinetic (PK) data on the ticagrelor 60 mg bid dosing regimen. In particular, there is no prospective PK/PD study on this dosing regimen in patients with DM who are known to have impaired response to clopidogrel therapy. Since DM patients frequently require elective PCI due to chronic progression of CAD (and not solely because of an acute thrombotic complication), and clopidogrel remains the guideline recommended P2Y12 inhibiting therapy for these patients, understanding the PD effects of the ticagrelor 60 mg bid regimen in this setting is an unmet clinical need. This is also in light of the ongoing THEMIS trial which is specifically evaluating the impact of the ticagrelor 60 mg bid dosing regimen in type 2 DM patients without a prior major CV event.

Conditions

Diabetes Mellitus, Type 2; Coronary Artery Disease

Keywords

diabetes mellitus; percutaneous coronary intervention; ticagrelor; clopidogrel; coronary artery disease

Outcome Measures

Primary Outcomes (1)

• P2Y12 Reaction Units (PRU)

  The primary endpoint of our study will be platelet reactivity, measured as PRU level using VerifyNow PRU, of ticagrelor versus clopidogrel MD at 30 days after PCI, immediately pre-dosing dosing (trough levels). PRU is a marker of platelet reactivity. Higher PRU values correspond to higher aggregation and lower response to antiplatelet therapy.

  30 days

Secondary Outcomes (1)

• Platelet Reactivity Index (PRI)

  30 days

Study Arms (2)

Ticagrelor

EXPERIMENTAL

180 mg loading dose (LD) followed by a 60 mg bid maintenance (MD) starting 12 h (± 1 h) after the LD

Drug: Ticagrelor

Clopidogrel

ACTIVE COMPARATOR

600 mg LD followed by a 75 mg od MD starting 24 hours (± 1 h) after the LD

Drug: Clopidogrel

Interventions

Ticagrelor DRUG

After providing written informed consent and following diagnostic angiography, patients meeting study entry criteria undergoing PCI will be randomly assigned in a 1:1 ratio to treatment with either ticagrelor or clopidogrel. Randomized treatment will be maintained for 30±3 days.

Also known as: Brilinta

Ticagrelor

Clopidogrel DRUG

After providing written informed consent and following diagnostic angiography, patients meeting study entry criteria undergoing PCI will be randomly assigned in a 1:1 ratio to treatment with either ticagrelor or clopidogrel. Randomized treatment will be maintained for 30±3 days.

Also known as: Plavix

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 drug (oral medications and / or insulin) treatment for at least 1 month
• Presence of CAD undergoing elective PCI\* \* Patients will need to be cardiac enzyme-negative prior to undergoing coronary angiography. Patient will need to be on a background of aspirin therapy (treated with a 325 mg LD prior to coronary angiography unless already on chronic low-dose aspirin therapy). Patients on maintenance clopidogrel 75 mg therapy for at least 1 week due to a prior vascular intervention will also be eligible. However, patients on clopidogrel, ticagrelor or prasugrel due to a prior acute major cardiovascular event (MI or stroke) will not be eligible.

You may not qualify if:

• Previous MI (with the exception of definite non-type 1 MI \[eg, due to coronary revascularization procedure, profound hypotension, hypertensive emergency, tachycardia, or profound anemia\])
• Previous stroke (transient ischemic attack \[TIA\] is not included in the stroke definition)
• Use of an intravenous antiplatelet therapy (i.e., cangrelor or GPI) during PCI
• On treatment with clopidogrel, prasugrel, or ticagrelor due to a prior acute major CV event (MI or stroke) (on treatment with clopidogrel due to prior vascular intervention not secondary to a major CV event is allowed)
• Planned use of aspirin treatment at doses \>100 mg od
• 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
• 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 ticagrelor and clopidogrel or any of the excipients
• 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 (eg, ascites and/or clinical signs of coagulopathy)

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; 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; Ticlopidine; Thienopyridines; Thiophenes; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring

Results Point of Contact

• Title: Dominick J. Angiolillo, MD, PhD
• Organization: University of Florida

dominick.angiolillo@jax.ufl.edu

9042443378

Study Officials

• Dominick J Angiolillo, MD,PhD

  University of Florida

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

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: February 12, 2018
• First Posted: February 19, 2018
• Study Start: March 14, 2018
• Primary Completion: June 27, 2019
• Study Completion: June 27, 2020
• Last Updated: November 30, 2021
• Results First Posted: February 5, 2021

Record last verified: 2021-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)