Influence of Morphine on Pharmacokinetics and Pharmacodynamics of Ticagrelor in Patients With Acute Myocardial Infarction (IMPRESSION)

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by Collegium Medicum w Bydgoszczy
Sponsor:
Information provided by (Responsible Party):
Jacek Kubica, Collegium Medicum w Bydgoszczy
ClinicalTrials.gov Identifier:
NCT02217878
First received: August 14, 2014
Last updated: September 24, 2014
Last verified: September 2014
  Purpose

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.


Condition Intervention Phase
ST-segment Elevation Myocardial Infarction
Non-ST-segment Elevation Myocardial Infarction
VA Drug Interactions [VA Drug Interaction]
Drug: Morphine
Drug: Placebo
Drug: Ticagrelor
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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.

Resource links provided by NLM:


Further study details as provided by Collegium Medicum w Bydgoszczy:

Primary Outcome Measures:
  • Area under the plasma concentration-time curve for ticagrelor (AUC 0-24h) [ Time Frame: prior to the initial dose and 30min, 1h, 2h, 3h, 4h, 6h, 12h, 24h post dose ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Area under the plasma concentration-time curve for AR-C124910XX (AUC 0-24h) [ Time Frame: prior to the initial dose and 30min, 1h, 2h, 3h, 4h, 6h, 12h, 24h post dose ] [ Designated as safety issue: No ]
  • Maximum concentration (Cmax) of ticagrelor and AR-C124910XX [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
  • Time to maximum concentration (Cmax) for ticagrelor and AR-C124910XX [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
  • Platelet reactivity index (PRI) assessed by VASP assay [ Time Frame: prior to the initial dose and 30min, 1h, 2h, 3h, 4h, 6h, 12h, 24h post dose ] [ Designated as safety issue: No ]
    It will be assessed in all study participants in all predefined time points.

  • Platelet arbitrary aggregation units/min assessed by Multiple Electrode Aggregometry [ Time Frame: prior to the initial dose and 30min, 1h, 2h, 3h, 4h, 6h, 12h, 24h post dose ] [ Designated as safety issue: No ]
    It will be assessed in all predefined time points in all study participants except those treated with GP IIb/IIIa receptor inhibitors.

  • P2Y12 Reaction Units (PRU) assessed by VerifyNow [ Time Frame: prior to the initial dose and 30min, 1h, 2h, 3h, 4h, 6h, 12h, 24h post dose ] [ Designated as safety issue: No ]
    It will be assessed in at least 30% of study participants (with 1:1 ratio between morphine and placebo arms) in all predefined time points. Measurements will not be performed in patients treated with GP IIb/IIIa receptor inhibitors.

  • ADP-induced platelet aggregation assessed by light transmission aggregometry [ Time Frame: prior to the initial dose and 30min, 1h, 2h, 3h, 4h, 6h, 12h, 24h post dose ] [ Designated as safety issue: No ]
    It will be assessed in at least 30% of study participants (with 1:1 ratio between morphine and placebo arms) in all predefined time points. Measurements will not be performed in patients treated with GP IIb/IIIa receptor inhibitors.


Estimated Enrollment: 100
Study Start Date: August 2014
Estimated Study Completion Date: February 2016
Estimated Primary Completion Date: February 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Morphine
morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor
Drug: Morphine
IV bolus injection
Other Name: Morphine sulfate
Drug: Ticagrelor
180 mg loading dose
Other Name: Brilique
Placebo Comparator: Placebo
sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor
Drug: Placebo
IV bolus injection
Other Name: Sodium chloride 0,9%
Drug: Ticagrelor
180 mg loading dose
Other Name: Brilique

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).

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02217878

Contacts
Contact: Piotr Adamski, MD +48525854023 piotr.adamski@wp.eu

Locations
Poland
Cardiology Department, Dr. A. Jurasz University Hospital Recruiting
Bydgoszcz, Kujawsko-pomorskie, Poland, 85-094
Contact: Piotr Adamski, MD    +48525854023    piotr.adamski@wp.eu   
Sub-Investigator: Piotr Adamski, MD         
Sub-Investigator: Małgorzata Ostrowska, MD         
Sponsors and Collaborators
Collegium Medicum w Bydgoszczy
Investigators
Principal Investigator: Prof. Jacek Kubica, MD, PhD Collegium Medicum im. Ludwika Rydygiera w Bydgoszczy, Uniwersytet Mikołaja Kopernika w Toruniu
  More Information

No publications provided

Responsible Party: Jacek Kubica, Prof. dr hab., Collegium Medicum w Bydgoszczy
ClinicalTrials.gov Identifier: NCT02217878     History of Changes
Other Study ID Numbers: CMUMK202
Study First Received: August 14, 2014
Last Updated: September 24, 2014
Health Authority: Poland: Ethics Committee

Keywords provided by Collegium Medicum w Bydgoszczy:
ST-segment elevation myocardial infarction
non-ST-segment elevation myocardial infarction
ticagrelor
morphine
pharmacokinetics
pharmacodynamics
drug interactions
VASP assay
Multiple Electrode Aggregometry
VerifyNow
light transmission aggregometry

Additional relevant MeSH terms:
Infarction
Myocardial Infarction
Cardiovascular Diseases
Heart Diseases
Ischemia
Myocardial Ischemia
Necrosis
Pathologic Processes
Vascular Diseases
Morphine
Ticagrelor
Analgesics
Analgesics, Opioid
Central Nervous System Agents
Central Nervous System Depressants
Molecular Mechanisms of Pharmacological Action
Narcotics
Neurotransmitter Agents
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Purinergic Agents
Purinergic Antagonists
Purinergic P2 Receptor Antagonists
Purinergic P2Y Receptor Antagonists
Sensory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 21, 2014