Influence of Morphine on Pharmacokinetics and Pharmacodynamics of Ticagrelor in Patients With Acute Myocardial Infarction
Information source: Collegium Medicum w Bydgoszczy
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: ST-segment Elevation Myocardial Infarction; Non-ST-segment Elevation Myocardial Infarction; VA Drug Interactions [VA Drug Interaction]
Intervention: Morphine (Drug); Placebo (Drug); Ticagrelor (Drug)
Phase: Phase 4
Status: Recruiting
Sponsored by: Collegium Medicum w Bydgoszczy Official(s) and/or principal investigator(s): Prof. Jacek Kubica, MD, PhD, Principal Investigator, Affiliation: Collegium Medicum im. Ludwika Rydygiera w Bydgoszczy, Uniwersytet Mikołaja Kopernika w Toruniu
Overall contact: Piotr Adamski, MD, Phone: +48525854023, Email: piotr.adamski@wp.eu
Summary
The purpose of the IMPRESSION study is to determine whether intravenous administration of
morphine prior to ticagrelor administration in ST-segment elevation myocardial infarction
(STEMI) patients and in non-ST-segment elevation myocardial infarction (NSTEMI) patients
alters the plasma concentrations of ticagrelor and its active metabolite and whether it is
associated with any negative impact on the antiplatelet effect of ticagrelor.
Clinical Details
Official title: A Randomized, Double-blind Study Evaluating the Influence of Morphine on Pharmacokinetics and Pharmacodynamics of Ticagrelor and Its Active Metabolite (AR-C124910XX) in Patients With ST-segment Elevation Myocardial Infarction and Non-ST-segment Elevation Myocardial Infarction.
Study design: Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Primary outcome: Area under the plasma concentration-time curve for ticagrelor (AUC 0-12h)
Secondary outcome: Area under the plasma concentration-time curve for AR-C124910XX (AUC 0-12h)Maximum concentration (Cmax) of ticagrelor and AR-C124910XX Time to maximum concentration (Cmax) for ticagrelor and AR-C124910XX Platelet reactivity index (PRI) assessed by VASP assay Platelet arbitrary aggregation units/min assessed by Multiple Electrode Aggregometry P2Y12 Reaction Units (PRU) assessed by VerifyNow Area under the plasma concentration-time curve for ticagrelor (AUC 0-6h) Area under the plasma concentration-time curve for AR-C124910XX (AUC 0-6) Percentage of patients with high platelet reactivity (HPR) after the loading dose of ticagrelor assessed with VASP, MEA and VerifyNow Time to reach platelet reactivity below the cut-off value for high platelet reactivity (HPR) evaluated with VASP, MEA and VerifyNow
Detailed description:
The European Society of Cardiology and American Heart Association guidelines recommend use
of morphine as a treatment of choice for pain relief in STEMI patients. However, this
recommendation, although strong, is only based on expert consensus (class of recommendation
I, level of evidence C). Morphine, apart from its analgesic effects, also alleviates the
work of breathing and reduces anxiety. On the other hand, despite its favorable analgesic
and sedative actions, morphine also exerts adverse effects, which include hypotension,
bradycardia, respiratory depression, vomiting and reduction of gastrointestinal motility.
Some of the previously listed morphine's side effects could affect the intestinal absorption
and thus pharmacokinetics and pharmacodynamics of orally administered drugs which are
concomitantly used with morphine. At present, no pharmacokinetic and pharmacodynamic data
regarding the concurrent use of morphine and P2Y12 blockers in the STEMI or NSTEMI setting
are available. Therefore, evidence-based verification of morphine's influence on
pharmacokinetics and pharmacodynamics of ticagrelor and its active metabolite (AR-C124910XX)
could provide a valuable insight in the knowledge regarding modern acute myocardial
infarction management.
Predefined subanalysis: aimed to investigate which one of platelet reactivity assessment
methods utilized in the study (VASP assay, MEA, LTA, VerifyNow) best reflects concentration
of ticagrelor and its active metabolite (AR-C124910XX).
Since there is no reference study examining pharmacokinetics of ticagrelor in STEMI or
NSTEMI patients, we decided to perform an internal pilot study of approximately 30 patients
(15 patients for each arm) for estimating the final sample size.
Eligibility
Minimum age: 18 Years.
Maximum age: 80 Years.
Gender(s): Both.
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
elevation myocardial infarction
- male or non-pregnant female, aged 18-80 years old
- provision of informed consent for angiography and PCI
Exclusion Criteria:
- chest pain described by the patient as unbearable or patient's request for analgesics
- prior morphine administration during the current STEMI or NSTEMI
- 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
Locations and Contacts
Piotr Adamski, MD, Phone: +48525854023, Email: piotr.adamski@wp.eu
Cardiology Department, Dr. A. Jurasz University Hospital, Bydgoszcz, Kujawsko-pomorskie 85-094, Poland; Recruiting Piotr Adamski, MD, Phone: +48525854023, Email: piotr.adamski@wp.eu Piotr Adamski, MD, Sub-Investigator Małgorzata Ostrowska, MD, Sub-Investigator
Additional Information
Starting date: August 2014
Last updated: June 29, 2015
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