Influence of Naloxone on Ticagrelor Pharmacokinetics and Pharmacodynamics in Patients With Unstable Angina Pectoris on Concomitant Treatment With Morphine

Collegium Medicum w Bydgoszczy

Status and phase

Completed

Phase 4

Conditions

Unstable Angina Pectoris

Treatments

Drug: Crushed ticagrelor followed by morphine

Drug: Crushed ticagrelor, morphine,naloxone

Study type

Interventional

Funder types

Other

Identifiers

NCT02939248

CMUMK202G

Details and patient eligibility

About

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 naloxone versus patients treated with ticagrelor and morphine alone for unstable angina pectoris.

Full description

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 orally administered naloxone 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.

Enrollment

30 patients

Sex

All

Ages

18 to 80 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Provision of informed consent prior to any study specific procedures
Diagnosis of unstable angina
Male or non-pregnant female, aged 18-80 years
Provision of informed consent for angiography and PCI
GRACE score <140 pts

Exclusion criteria

treatment with ticlopidine, clopidogrel, prasugrel or ticagrelor within 14 days before the study enrollment
current treatment with morphine or any opioid "mi" receptor agonist
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)
risk of bradycardic events as judged by the investigator
second or third degree atrioventricular block during screening for eligibility
history of asthma or severe chronic obstructive pulmonary disease
kidney disease requiring 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