Kubica Jacek, Adamski Piotr, Ostrowska Małgorzata, Koziński Marek, Obońska Karolina, Laskowska Ewa, Obońska Ewa, Grześk Grzegorz, Winiarski Piotr, Paciorek Przemysław
Department of Cardiology and Internal Medicine, Nicolaus Copernicus University, Collegium Medicum, 9 Skłodowskiej-Curie Street, 85-094, Bydgoszcz, Poland.
Department of Principles of Clinical Medicine, Nicolaus Copernicus University, Collegium Medicum, 9 Skłodowskiej-Curie Street, 85-094, Bydgoszcz, Poland.
Trials. 2015 Apr 29;16:198. doi: 10.1186/s13063-015-0724-z.
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).
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.
ClinicalTrials.gov identifier: NCT02217878 (14 August 2014).
替格瑞洛是一种口服血小板P2Y12受体拮抗剂，推荐用于患有心肌梗死的患者，无论有无持续性ST段抬高。吗啡是同一临床亚组中缓解疼痛的首选药物。最近有人推测吗啡可能对P2Y12受体阻滞剂的药代动力学和抗血小板作用产生负面影响。
方法/设计：IMPRESSION研究是一项IV期、单中心、随机、双盲、安慰剂对照临床试验，旨在评估吗啡对心肌梗死患者替格瑞洛药代动力学和药效学的影响。该研究计划纳入多达100名心肌梗死患者，他们将按1:1的比例随机分为两组。替格瑞洛负荷剂量（180mg）前，干预组的受试者将静脉注射吗啡（5mg），而对照组的患者在替格瑞洛负荷剂量（180mg）前将接受安慰剂。替格瑞洛及其活性代谢物（AR-C124910XX）的药代动力学将通过液相色谱质谱法进行评估。每位患者的血小板功能测试将使用多达四种不同的方法（血小板血管舒张刺激磷蛋白测定、多电极聚集测定、VerifyNow和光透射聚集测定）。
本研究有望提供关于吗啡对心肌梗死患者替格瑞洛吸收影响的重要循证数据，并阐明同一组患者中吗啡使用与替格瑞洛抗血小板活性之间的疑似联系。
ClinicalTrials.gov标识符：NCT02217878（2014年8月14日）。
