Influence of Morphine on Pharmacokinetics and Pharmacodynamics of Ticagrelor in Patients with Acute Myocardial Infarction (IMPRESSION): study protocol for a randomized controlled trial.
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
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).


CONCLUSIONS
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.


BACKGROUND
ClinicalTrials.gov identifier: NCT02217878 (14 August 2014).
Department of Cardiology and Internal Medicine, Nicolaus Copernicus University, Collegium Medicum, 9 Skłodowskiej-Curie Street, 85-094, Bydgoszcz, Poland. jkubica@cm.umk.pl.
Jacek
J
Kubica
Department of Principles of Clinical Medicine, Nicolaus Copernicus University, Collegium Medicum, 9 Skłodowskiej-Curie Street, 85-094, Bydgoszcz, Poland. piotr.adamski@wp.eu.
Piotr
P
Adamski
Department of Principles of Clinical Medicine, Nicolaus Copernicus University, Collegium Medicum, 9 Skłodowskiej-Curie Street, 85-094, Bydgoszcz, Poland. ostrowska.go@gmail.com.
Małgorzata
M
Ostrowska
Department of Principles of Clinical Medicine, Nicolaus Copernicus University, Collegium Medicum, 9 Skłodowskiej-Curie Street, 85-094, Bydgoszcz, Poland. marekkozinski@wp.pl.
Marek
M
Koziński
Department of Cardiology and Internal Medicine, Nicolaus Copernicus University, Collegium Medicum, 9 Skłodowskiej-Curie Street, 85-094, Bydgoszcz, Poland. kalaobonska@op.pl.
Karolina
K
Obońska
Department of Principles of Clinical Medicine, Nicolaus Copernicus University, Collegium Medicum, 9 Skłodowskiej-Curie Street, 85-094, Bydgoszcz, Poland. laskowskaewa1@gmail.com.
Ewa
E
Laskowska
Department of Pharmacology and Therapy, Nicolaus Copernicus University, Collegium Medicum, 9 Skłodowskiej-Curie Street, 85-094, Bydgoszcz, Poland. ewaobonska@onet.eu.
Ewa
E
Obońska
Department of Pharmacology and Therapy, Nicolaus Copernicus University, Collegium Medicum, 9 Skłodowskiej-Curie Street, 85-094, Bydgoszcz, Poland. ggrzesk@cm.umk.pl.
Grzegorz
G
Grześk
Dr. J. Biziel Memorial University Hospital No. 2, 75 Ujejskiego Street, 85-168, Bydgoszcz, Poland. otolaryngologia@biziel.pl.
Piotr
P
Winiarski
Department of Cardiology and Internal Medicine, Nicolaus Copernicus University, Collegium Medicum, 9 Skłodowskiej-Curie Street, 85-094, Bydgoszcz, Poland. p.paciorek@wp.pl.
Przemysław
P
Paciorek
D000241:Adenosine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D000368:Aged; D000701:Analgesics, Opioid / Q000008:administration & dosage*; D001711:Biotransformation; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D002853:Chromatography, Liquid; D002985:Clinical Protocols; D004311:Double-Blind Method; D004347:Drug Interactions; D016903:Drug Monitoring / Q000379:methods; D005260:Female; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D009020:Morphine / Q000008:administration & dosage*; D009203:Myocardial Infarction / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D010979:Platelet Function Tests; D011044:Poland; D058921:Purinergic P2Y Receptor Antagonists / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D012107:Research Design; D000077486:Ticagrelor; D016896:Treatment Outcome
C561701:AR C124910XX; D000701:Analgesics, Opioid; D010975:Platelet Aggregation Inhibitors; D058921:Purinergic P2Y Receptor Antagonists; D009020:Morphine; D000077486:Ticagrelor; D000241:Adenosine