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

NCT ID: NCT02939248

Last Updated: 2019-04-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-10-31
• Study Completion Date: 2018-12-31

Brief Summary

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.

Detailed 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.

Conditions

Unstable Angina Pectoris

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Crushed ticagrelor followed by morphine

crushed ticagrelor 180 mg administered orally followed by morphine 5 mg intravenously

Group Type: ACTIVE_COMPARATOR

Crushed ticagrelor followed by morphine

Intervention Type: DRUG

Crushed ticagrelor (180 mg) followed by morphine 5 mg intravenously

Crushed ticagrelor, morphine,naloxone

crushed ticagrelor 180 mg administered orally followed by morphine 5 mg intravenously and naloxone 1 mg orally

Group Type: ACTIVE_COMPARATOR

Crushed ticagrelor, morphine,naloxone

Intervention Type: DRUG

Crushed ticagrelor (180 mg) orally followed by morphine 5 mg intravenously and naloxone 1 mg orally

Interventions

Crushed ticagrelor followed by morphine

Crushed ticagrelor (180 mg) followed by morphine 5 mg intravenously

Intervention Type: DRUG

Crushed ticagrelor, morphine,naloxone

Crushed ticagrelor (180 mg) orally followed by morphine 5 mg intravenously and naloxone 1 mg orally

Intervention Type: DRUG

Other Intervention Names

Brilique; Brilique

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Collegium Medicum w Bydgoszczy

OTHER

Sponsor Role: lead

Responsible Party

Jacek Kubica

Prof. Jacek Kubica, MD, PhD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jacek Kubica, MD., PhD.

Role: PRINCIPAL_INVESTIGATOR

Cardiology Department, Dr. A. Jurasz University Hospital

Locations

Cardiology Department, Dr. A. Jurasz University Hospital

Bydgoszcz, Kuyavian-Pomeranian Voivodeship, Poland

Countries

Poland

Other Identifiers

CMUMK202G

Identifier Type: -

Identifier Source: org_study_id