Influence of Morphine on Pharmacokinetics and Pharmacodynamics of Ticagrelor in
Patients with Acute Myocardial Infarction (IMPRESSION): study protocol for a
randomized controlled trial.
Author(s): Kubica J(1), Adamski P(2), Ostrowska M(3), Koziński M(4), Obońska K(5), Laskowska
E(6), Obońska E(7), Grześk G(8), Winiarski P(9), Paciorek P(10).
Affiliation(s): Author information:
(1)Department of Cardiology and Internal Medicine, Nicolaus Copernicus
University, Collegium Medicum, 9 Skłodowskiej-Curie Street, 85-094, Bydgoszcz,
Poland. jkubica@cm.umk.pl. (2)Department of Principles of Clinical Medicine,
Nicolaus Copernicus University, Collegium Medicum, 9 Skłodowskiej-Curie Street,
85-094, Bydgoszcz, Poland. piotr.adamski@wp.eu. (3)Department of Principles of
Clinical Medicine, Nicolaus Copernicus University, Collegium Medicum, 9
Skłodowskiej-Curie Street, 85-094, Bydgoszcz, Poland. ostrowska.go@gmail.com.
(4)Department of Principles of Clinical Medicine, Nicolaus Copernicus University,
Collegium Medicum, 9 Skłodowskiej-Curie Street, 85-094, Bydgoszcz, Poland.
marekkozinski@wp.pl. (5)Department of Cardiology and Internal Medicine, Nicolaus
Copernicus University, Collegium Medicum, 9 Skłodowskiej-Curie Street, 85-094,
Bydgoszcz, Poland. kalaobonska@op.pl. (6)Department of Principles of Clinical
Medicine, Nicolaus Copernicus University, Collegium Medicum, 9 Skłodowskiej-Curie
Street, 85-094, Bydgoszcz, Poland. laskowskaewa1@gmail.com. (7)Department of
Pharmacology and Therapy, Nicolaus Copernicus University, Collegium Medicum, 9
Skłodowskiej-Curie Street, 85-094, Bydgoszcz, Poland. ewaobonska@onet.eu.
(8)Department of Pharmacology and Therapy, Nicolaus Copernicus University,
Collegium Medicum, 9 Skłodowskiej-Curie Street, 85-094, Bydgoszcz, Poland.
ggrzesk@cm.umk.pl. (9)Dr. J. Biziel Memorial University Hospital No. 2, 75
Ujejskiego Street, 85-168, Bydgoszcz, Poland. otolaryngologia@biziel.pl.
(10)Department of Cardiology and Internal Medicine, Nicolaus Copernicus
University, Collegium Medicum, 9 Skłodowskiej-Curie Street, 85-094, Bydgoszcz,
Poland. p.paciorek@wp.pl.
Publication date & source: 2015, Trials. , 16:198
BACKGROUND: Ticagrelor is an oral platelet P2Y12 receptor antagonist which is
recommended for patients suffering from myocardial infarction, both with and
without persistent ST segment elevation. Morphine is the first choice drug in
pain alleviation in the same clinical subset. Recently a possible negative
influence of morphine on the pharmacokinetics and antiplatelet effects of P2Y12
receptor blockers has been postulated.
METHODS/DESIGN: The IMPRESSION study is a phase IV, single center, randomized,
double-blind, placebo-controlled clinical trial that is designed to assess the
influence of morphine on the pharmacokinetics and pharmacodynamics of ticagrelor
in patients with myocardial infarction. The study is planned to include up to 100
patients with myocardial infarction who will be randomized into one of two arms
in a 1:1 ratio. Subjects in the intervention arm prior to the loading dose of
ticagrelor (180 mg) will receive morphine (5 mg) intravenously, whereas patients
in the control arm will receive a placebo prior to the loading dose of ticagrelor
(180 mg). The pharmacokinetics of ticagrelor and its active metabolite
(AR-C124910XX) will be assessed by liquid chromatography mass spectrometry.
Platelet function testing in each patient will be performed using up to four
different methods (platelet vasodilator-stimulated phosphoprotein assay, multiple
electrode aggregometry, VerifyNow, and light transmission aggregometry).
DISCUSSION: This study is expected to provide essential evidence-based data on
the impact of morphine on the absorption of ticagrelor in patients with
myocardial infarction as well as to shed some light on the suspected connection
between morphine use and antiplatelet activity of ticagrelor in the same group of
patients.
TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02217878 (14 August 2014).
|
