Comparison of Ticagrelor Pharmacokinetics and Pharmacodynamics in STEMI and NSTEMI Patients

Study Overview
=================
Brief Summary
-----------------
The purpose of the PINPOINT study is to compare pharmacokinetics (PK) and pharmacodynamics (PD) of ticagrelor in ST-elevation myocardial infarction (STEMI) and non-ST-elevation myocardial infarction (NSTEMI) patients designated to invasive strategy. Data regarding comparison of PK and antiplatelet action of ticagrelor in STEMI and NSTEMI are sparse. Recommended dosing regimens of ticagrelor are identical for both STEMI and NSTEMI, although it is not known whether PK and PD features of ticagrelor are uniform in these patients.

Detailed Description
-----------------
The European Society of Cardiology and American Heart Association guidelines recommend use of ticagrelor or prasugrel as a treatment of choice in patients with both STEMI and NSTEMI (class of recommendation I, level of evidence B). Recommended dosing regimens of ticagrelor are identical in STEMI and NSTEMI patients, although epidemiology, clinical approach and early outcomes differ between these two types of myocardial infarction. It is not known whether PK and PD features of ticagrelor are uniform in STEMI and NSTEMI patients. However, the existing body of evidence suggest that PK and PD of ticagrelor may be attenuated in STEMI patients compared to healthy subjects and patients with stable coronary artery disease, which may expose STEMI patients at increased risk of developing thrombotic complications secondary to insufficient platelet inhibition. The PINPOINT study could provide a valuable insight into the knowledge regarding ticagrelor action in STEMI vs. NSTEMI patients. Since there is no reference study comparing pharmacokinetics of ticagrelor in STEMI and NSTEMI patients, we decided to perform an internal pilot study of approximately 30 patients (15 patients with each type of myocardial infarction) for estimating the final sample size.

Official Title
-----------------
Comparison of Ticagrelor Pharmacokinetics and Pharmacodynamics in ST-elevation Myocardial Infarction and Non-ST-elevation Myocardial Infarction Patients

Conditions
-----------------
Myocardial Infarction

Intervention / Treatment
-----------------
* Drug: ticagrelor


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: provision of informed consent prior to any study specific procedures diagnosis of acute ST-segment elevation myocardial infarction or acute non-ST-segment elevation myocardial infarction male or non-pregnant female, 18 years old and older provision of informed consent for angiography and PCI Exclusion Criteria: treatment with ticlopidine, clopidogrel, prasugrel or ticagrelor within 14 days before the study enrollment hypersensitivity to ticagrelor current treatment with oral anticoagulant or chronic therapy with low-molecular-weight heparin active bleeding history of intracranial hemorrhage recent gastrointestinal bleeding (within 30 days) history of coagulation disorders history of moderate or severe hepatic impairment history of major surgery or severe trauma (within 3 months) second or third degree atrioventricular block during screening for eligibility patient required dialysis manifest infection or inflammatory state Killip class III or IV during screening for eligibility respiratory failure current therapy with strong CYP3A inhibitors or strong CYP3A inducers

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| STEMI<br>ST-elevation myocardial infarction patients receiving 180 mg ticagrelor loading dose | Drug: ticagrelor<br>* 180 mg loading dose<br>* Other names: Brilique;|
| NSTEMI<br>non-ST-elevation myocardial infarction patients receiving 180 mg ticagrelor loading dose | Drug: ticagrelor<br>* 180 mg loading dose<br>* Other names: Brilique;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the plasma concentration-time curve for ticagrelor (AUC 0-6h) |  | prior to the initial dose and 30min, 1h, 2h, 3h, 4h, 6h post dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the plasma concentration-time curve for AR-C124910XX (AUC 0-6h) |  | prior to the initial dose and 30min, 1h, 2h, 3h, 4h, 6h post dose | 
| Area under the plasma concentration-time curve for ticagrelor (AUC 0-12h) |  | prior to the initial dose and 30min, 1h, 2h, 3h, 4h, 6h, 12h post dose | 
| Area under the plasma concentration-time curve for AR-C124910XX (AUC 0-12h) |  | prior to the initial dose and 30min, 1h, 2h, 3h, 4h, 6h, 12h post dose | 
| Maximum concentration (Cmax) of ticagrelor and AR-C124910XX |  | 12 hours | 
| Time to maximum concentration (Cmax) for ticagrelor and AR-C124910XX |  | 12 hours | 
| Platelet reactivity index (PRI) assessed by VASP assay |  | prior to the initial dose and 30min, 1h, 2h, 3h, 4h, 6h, 12h post dose | 
| Platelet reactivity assessed by Multiple Electrode Aggregometry | It will be assessed in all predefined time points in all study participants except those treated with GP IIb/IIIa receptor inhibitors. | prior to the initial dose and 30min, 1h, 2h, 3h, 4h, 6h, 12h post dose | 
| Percentage of patients with high platelet reactivity (HPR) after the loading dose of ticagrelor assessed with VASP and Multiple Electrode Aggregometry |  | 2 hours | 
| Time to reach platelet reactivity below the cut-off value for HPR evaluated with VASP and Multiple Electrode Aggregometry |  | 12 hours | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
ticagrelor, STEMI, NSTEMI, pharmacokinetics, pharmacodynamics