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Ticagrelor With and Without Aspirin in Patients With Diabetes Mellitus (OPTIMUS-7)

Primary Purpose

Diabetes Mellitus, Type 2, Coronary Artery Disease

Status

Recruiting

Phase

Phase 4

Locations

United States

Study Type

Interventional

Intervention

Ticagrelor monotherapy

Ticagrelor plus aspirin

Clopidogrel with aspirin

About this trial

This is an interventional treatment trial for Diabetes Mellitus, Type 2 focused on measuring diabetes mellitus, ticagrelor, clopidogrel, percutaneous coronary intervention

Eligibility Criteria

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

Inclusion criteria:

For inclusion in the study patients should fulfill the following criteria:

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 CAD with a history of previous PCI 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).

Exclusion criteria:

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
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
Known hemoglobin <9 g/dL
Pregnant or breastfeeding women. *Women of childbearing age must use reliable birth control (i.e. oral contraceptives) while participating in the study.

Sites / Locations

University of FloridaRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Active Comparator

Arm Label

Ticagrelor

Aspirin plus Clopidogrel

Aspirin plus Ticagrelor

Arm Description

ticagrelor 60 mg bid monotherapy

aspirin 81 mg qd plus clopidogrel 75 mg qd

aspirin 81 mg qd plus ticagrelor 60 mg bid

Outcomes

Primary Outcome Measures

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)

Secondary Outcome Measures

Full Information

NCT ID

NCT04484259

First Posted

July 21, 2020

Last Updated

June 7, 2023

Sponsor

University of Florida

Collaborators

AstraZeneca

1. Study Identification

Unique Protocol Identification Number

NCT04484259

Brief Title

Ticagrelor With and Without Aspirin in Patients With Diabetes Mellitus

Acronym

OPTIMUS-7

Official Title

Pharmacodynamic Effects of Different Ticagrelor Maintenance Dosing Regimens With and Without Aspirin in Patients With Diabetes Mellitus: The OPTIMUS (Optimizing Antiplatelet Therapy in Diabetes Mellitus)-7 Study

Study Type

Interventional

2. Study Status

Record Verification Date

June 2023

Overall Recruitment Status

Recruiting

Study Start Date

March 31, 2021 (Actual)

Primary Completion Date

May 2024 (Anticipated)

Study Completion Date

August 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University of Florida

Collaborators

AstraZeneca

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

Yes

5. Study Description

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.

Detailed Description

Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 inhibitor is the standard of care for the prevention of thrombotic complications in patients with coronary artery disease (CAD) undergoing percutaneous coronary interventions (PCI). However, such ischemic benefit occurs at the expense of enhanced bleeding, the risk of which increases in a graded fashion with prolonged exposure to DAPT. 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. In fact, current guidelines recommend maintaining P2Y12 inhibiting therapy for high risk patients but which all imply background use of aspirin. P2Y12 inhibitors for long-term (beyond 12 months) secondary prevention mainly include clopidogrel and ticagrelor. In particular, the dosing regimen for clopidogrel remains the standard 75 mg qd, whereas ticagrelor dosing is recommended to be reduced from 90 mg bid to 60 mg bid. However, of these regimens the pharmacodynamics (PD) effects of ticagrelor 60 mg in the absence of aspirin has not yet been tested. Because DM patients are likely to continue with long-term P2Y12 inhibitor therapy, defining the optimal antithrombotic approach for these patients is of critical importance. In light of the above made observations, patients with DM represent an ideal population to define the antiplatelet effects of a ticagrelor 60 mg monotherapy regimen. 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.

6. Conditions and Keywords

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

Diabetes Mellitus, Type 2, Coronary Artery Disease

Keywords

diabetes mellitus, ticagrelor, clopidogrel, percutaneous coronary intervention

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Model Description

Prospective randomized

Masking

None (Open Label)

Masking Description

Staff performing PK/PD assessments will remain blinded to treatment assignment.

Allocation

Randomized

Enrollment

63 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Ticagrelor

Arm Type

Experimental

Arm Description

ticagrelor 60 mg bid monotherapy

Arm Title

Aspirin plus Clopidogrel

Arm Type

Active Comparator

Arm Description

aspirin 81 mg qd plus clopidogrel 75 mg qd

Arm Title

Aspirin plus Ticagrelor

Arm Type

Active Comparator

Arm Description

aspirin 81 mg qd plus ticagrelor 60 mg bid

Intervention Type

Drug

Intervention Name(s)

Ticagrelor monotherapy

Other Intervention Name(s)

Brilinta

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Ticagrelor plus aspirin

Other Intervention Name(s)

Brilinta

Intervention Description

Intervention Type

Drug

Intervention Name(s)

Clopidogrel with aspirin

Other Intervention Name(s)

Plavix

Intervention Description

Primary Outcome Measure Information:

Title

P2Y12 reaction units (PRU)

Description

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)

Time Frame

10 days

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion criteria: For inclusion in the study patients should fulfill the following criteria: 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 CAD with a history of previous PCI 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). Exclusion criteria: 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 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 Known hemoglobin <9 g/dL Pregnant or breastfeeding women. *Women of childbearing age must use reliable birth control (i.e. oral contraceptives) while participating in the study.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Dominick J Angiolillo, MD,PhD

Phone

+1-904-244-3378

dominick.angiolillo@jax.ufl.edu

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Dominick J Angiolillo, MD,PhD

Organizational Affiliation

University of Florida

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of Florida

City

Jacksonville

State/Province

Florida

ZIP/Postal Code

32209

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Dominick J Angiolillo, MD, PhD

dominick.angiolillo@jax.ufl.edu

First Name & Middle Initial & Last Name & Degree

Dominick J Angiolillo, MD, PhD

First Name & Middle Initial & Last Name & Degree

Francesco Franchi, MD

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

Ticagrelor With and Without Aspirin in Patients With Diabetes Mellitus

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