Clinical trial NCT04484259: Ticagrelor With and Without Aspirin in Patients With Diabetes Mellitus
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
Overall status: COMPLETED
Phase: PHASE4
Conditions: Diabetes Mellitus, Type 2
Coronary Artery Disease
Keywords: diabetes mellitus
ticagrelor
clopidogrel
percutaneous coronary intervention
Lead sponsor: University of Florida
Sponsor class: OTHER
Collaborators: name: AstraZeneca
First posted: 2020-07-23
Enrollment: 105
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Prospective randomized
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion criteria:

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

1. Provision of informed consent prior to any study specific procedures
2. Men or women ≥18 years of age
3. Diagnosed with type 2 DM defined by ongoing glucose lowering therapy (oral medications and/or insulin) treatment for at least 1 month
4. 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).

Exclusion criteria:

1. PCI \< 6 months prior
2. Recent (\< 6 months) type I myocardial infarction
3. 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
4. Anticipated concomitant oral or intravenous therapry of strong CYP3A inducers (phenytoin, rifampin, phenobarb, carbamazepine)
5. Need for chronic oral anticoagulant therapy or chronic low-molecular-weight heparin (at venous thrombosis treatment not prophylaxis doses)
6. Patients with known bleeding diathesis or coagulation disorder
7. 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
8. Active pathological bleeding
9. Hypersensitivity to aspirin, ticagrelor or clopidogrel
10. 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
11. Known severe liver disease
12. Renal failure requiring dialysis
13. Known platelet count \<80x106/mL
14. Known hemoglobin \<9 g/dL
15. Pregnant or breastfeeding women. \*Women of childbearing age must use reliable birth control (i.e. oral contraceptives) while participating in the study.

Primary outcomes:
measure: P2Y12 Reaction Units (PRU)
timeFrame: Day 10, pre-dose
Secondary outcomes:
Other outcomes:
measure: VASP
timeFrame: Day 10, pre-dose
measure: 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.
timeFrame: Day 10, pre-dose
measure: Comparison of Thrombus Formation Measured by T-TAS Between Between Aspirin Plus Ticagrelor 60 mg and Ticagrelor 60 mg Monotherapy
timeFrame: Day 10, pre-dose
Locations:
city: Jacksonville
country: United States
facility: University of Florida
state: Florida
Study officials:
affiliation: University of Florida
name: Dominick J Angiolillo, MD,PhD
role: PRINCIPAL_INVESTIGATOR
References: