The purpose of this study is to evaluate differences in the pharmacokinetics and pharmacodynamics of ticagrelor and its active metabolite between patients who received ticagrelor and morphine followed by metoclopramide versus patients treated with ticagrelor and morphine alone for unstable angina pectoris.
According to contemporary guidelines, ticagrelor is a recommended antiplatelet agent in acute coronary syndromes, including unstable angina pectoris. Quick platelet inhibition plays pivotal role in the treatment of acute coronary syndromes. As evidenced in the IMPRESSION study, analgesia with morphine delays platelet inhibition in patients with acute myocardial infarction. On the other hand, the results of the MOJITO study prove that administration of crushed ticagrelor tablets leads to quicker platelet blockage. Taking the above into consideration, we created a pharmacokinetic/pharmacodynamic study aiming to evaluate differences between patients who received crushed ticagrelor orally followed by either 1) a combination of intravenous morphine and metoclopramide or 2) intravenous morphine alone. The primary study outcome is time needed for ticagrelor and its active metabolite to reach their maximum plasma concentration in each study arm. Secondary outcomes include ticagrelor and AR-C124900XX maximum concentration and the area under the plasma concentration curve for both agents. Platelet reactivity will be assessed with the Multiplate Analyzer in all study participants at nine predefined time points.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
32
Crushed ticagrelor (180 mg) followed by morphine 5 mg intravenously
Crushed ticagrelor (180 mg) orally followed by morphine 5 mg and metoclopramide 10 mg intravenously
Cardiology Department, Dr. A. Jurasz University Hospital
Bydgoszcz, Kuyavian-Pomeranian Voivodeship, Poland
Time to maximum concentration (tmax) for ticagrelor and AR-C124900XX for ticagrelor+morphine vs ticagrelor+morphine+metoclopramide arms
Time frame: 6 hours
Maximum ticagrelor and AR-C124900XX concentration at 6h after administration (Cmax6)
Time frame: 6 hours
Area under the plasma concentration-time curve for ticagrelor (AUC 0-6h)
Time frame: prior to the initial dose and 15 min, 30 min, 45 min, 1h, 2h, 3h, 4h, 6h post dose
Area under the plasma concentration-time curve for AR-C124900XX (AUC 0-6h)
Time frame: prior to the initial dose and 15 min, 30 min, 45 min, 1h, 2h, 3h, 4h, 6h post dose
Platelet arbitrary aggregation units/min assessed by Multiple Electrode Aggregometry
Time frame: prior to the initial dose and 30min, 1h, 2h, 3h, 4h, 6h post dose
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