Clinical trial NCT02690454: Which Platelet Function Test Best Reflects the In Vivo Plasma Concentrations of Ticagrelor and Its Active Metabolite?
Official title: Which Platelet Function Test Provides the Best Reflection of the in Vivo Plasma Concentrations of Ticagrelor and Its Active Metabolite? A Pharmacokinetic and Pharmacodynamic Study Including Patients With Myocardial Infarction.
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Infarction
Myocardial Infarction
Cardiovascular Diseases
Heart Diseases
Ischemia
Myocardial Ischemia
Necrosis
Pathologic Processes
Vascular Diseases
Keywords: ticagrelor
ticagrelor active metabolite (AR-C124910XX)
platelet function tests
the flow cytometric VASP assay
the VerifyNow® device
the Multiplate® analyzer
pharmacokinetics
pharmacodynamics
Multiplate® ADPtest
VerifyNow® PRUTest™
Platelet VASP/P2Y12 assay
Lead sponsor: Collegium Medicum w Bydgoszczy
Sponsor class: OTHER
First posted: 2016-02-24
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients with myocardial infarction

Brief summary: Ticagrelor is a direct-acting, reversible platelet P2Y12 receptor inhibitor recommended by the recent European Society of Cardiology guidelines in patients with acute coronary syndromes (ACS) (class of recommendation I, level of evidence B). Ticagrelor inhibits platelet function stronger, faster and more consistently than clopidogrel, the former standard of antiplatelet therapy. In the landmark PLATO trial (Study of PLATelet inhibition and patient Outcomes), ticagrelor therapy as compared with clopidogrel treatment was associated with the reduced occurrence of major adverse cardiovascular events and all-cause mortality, but also resulted in a small, but statistically significant, increase in the rate of major bleeding. The optimum choice of antiplatelet treatment, aimed to provide each patient with maximum protection against ischemic events, while minimizing the risk of bleeding complications, is the challenge of contemporary ACS therapy. The tool which may help physicians and facilitate clinical decision making is platelet function testing. According to the guidance of both European and American groups of experts, there are three currently recommended platelet function tests, namely the VerifyNow device, the Multiplate analyzer and the Vasodilator Stimulated Phosphoprotein Phosphorylation (VASP) assay. It needs to be emphasized that none of these three methods is preferred over others. So far there are no studies linking pharmacokinetic analysis of ticagrelor and its active metabolite with comparative evaluation of platelet reactivity. The aim of this trial is to assess the relationship between concentrations of ticagrelor and its active metabolite (AR-C124910XX) and results of all three recommended platelet function tests in patients with myocardial infarction. Patients who receive GP IIb/IIIa receptor inhibitor will be excluded from the primary analysis.

Statistical analysis: The correlation will be assessed using correlation coefficients and intraclass correlation coefficients. while the agreement between the results of the compared platelet function tests will be measured using the Kappa statistic and Bland-Altman analysis.


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
* male or non-pregnant female, aged 18-80 years old
* 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
* platelet count less than \<100 x10\^3/mcl
* hemoglobin concentration less than 10.0 g/dl
* history of moderate or severe hepatic impairment
* history of major surgery or severe trauma (within 3 months)
* patients considered by the investigator to be at risk of bradycardic events
* second or third degree atrioventricular block during screening for eligibility
* history of asthma or severe chronic obstructive pulmonary disease
* patient required dialysis
* manifest infection or inflammatory state
* Killip class III or IV during screening for eligibility
* respiratory failure
* history of severe chronic heart failure (NYHA class III or IV)
* concomitant therapy with strong CYP3A inhibitors (ketoconazole, itraconazole, voriconazole, telithromycin, clarithromycin, nefazadone, ritonavir, saquinavir, nelfinavir, indinavir, atazanavir) or strong CYP3A inducers (rifampicin, phenytoin, carbamazepine, dexamethasone, phenobarbital) within 14 days and during study treatment
* body weight below 50 kg

Primary outcomes:
measure: Correlation coefficient between ticagrelor plasma concentration and platelet reactivity measurement [platelet reactivity index (PRI), platelet arbitrary aggregation units/min and P2Y12 Reaction Units (PRU)].
timeFrame: predose, 1, 2, 3, 4, 6, 12, 24 hours post-dose
Secondary outcomes:
measure: Correlation coefficient between ticagrelor active metabolite (AR-C124910XX) plasma concentration and platelet reactivity measurement [platelet reactivity index (PRI), platelet arbitrary aggregation units/min and P2Y12 Reaction Units (PRU)].
timeFrame: predose, 1, 2, 3, 4, 6, 12, 24 hours post-dose
measure: Correlation coefficient between ticagrelor plasma concentration and inhibition of platelet reactivity assessed with VASP assay, Multiplate® analyzer and VerifyNow® device).
timeFrame: predose, 1, 2, 3, 4, 6, 12, 24 hours post-dose
measure: Correlation coefficient between ticagrelor active metabolite (AR-C124910XX) plasma concentration and inhibition of platelet reactivity assessed with VASP assay, Multiplate® analyzer and VerifyNow® device.
timeFrame: predose, 1, 2, 3, 4, 6, 12, 24 hours post-dose
measure: Kappa statistics assessing agreement between the platelet reactivity measurements performed with the VASP assay and the Multiplate® and VerifyNow® assays in terms of identification of patients with high on-ticagrelor platelet reactivity.
timeFrame: predose, 1, 2, 3, 4, 6, 12, 24 hours post-dose
measure: Kappa statistics assessing agreement between the platelet reactivity measurements performed with the Multiplate® assay and the VASP and VerifyNow® assays in terms of identification of patients with low on-ticagrelor platelet reactivity.
timeFrame: predose, 1, 2, 3, 4, 6, 12, 24 hours post-dose
measure: Correlation coefficient between the standardized values of platelet reactivity performed with the Multiplate® assay and the VASP and VerifyNow® assays.
timeFrame: predose, 1, 2, 3, 4, 6, 12, 24 hours post-dose
measure: Intraclass correlation coefficient between the standardized values of platelet reactivity performed with the Multiplate® assay and the VASP and VerifyNow® assays.
timeFrame: predose, 1, 2, 3, 4, 6, 12, 24 hours post-dose
measure: Blant-Altman analysis assessing agreement between the standardized values of platelet reactivity performed with the Multiplate® assay and the VASP and VerifyNow® assays.
timeFrame: predose, 1, 2, 3, 4, 6, 12, 24 hours post-dose
Other outcomes:
Locations:
city: Bydgoszcz
country: Poland
facility: Cardiology Department, Dr. A. Jurasz University Hospital
state: Kujawsko-pomorskie
Study officials:
References: