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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02939235
Recruitment Status : Completed
First Posted : October 19, 2016
Last Update Posted : April 1, 2019
Sponsor:
Information provided by (Responsible Party):
Jacek Kubica, Collegium Medicum w Bydgoszczy

Tracking Information
First Submitted Date  ICMJE October 18, 2016
First Posted Date  ICMJE October 19, 2016
Last Update Posted Date April 1, 2019
Study Start Date  ICMJE July 2016
Actual Primary Completion Date December 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 18, 2016)
Time to maximum concentration (tmax) for ticagrelor and AR-C124900XX for ticagrelor+morphine vs ticagrelor+morphine+metoclopramide arms [ Time Frame: 6 hours ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 18, 2016)
  • Maximum ticagrelor and AR-C124900XX concentration at 6h after administration (Cmax6) [ Time Frame: 6 hours ]
  • Area under the plasma concentration-time curve for ticagrelor (AUC 0-6h) [ Time Frame: prior to the initial dose and 15 min, 30 min, 45 min, 1h, 2h, 3h, 4h, 6h post dose ]
  • Area under the plasma concentration-time curve for AR-C124900XX (AUC 0-6h) [ Time Frame: prior to the initial dose and 15 min, 30 min, 45 min, 1h, 2h, 3h, 4h, 6h post dose ]
  • Platelet arbitrary aggregation units/min assessed by Multiple Electrode Aggregometry [ Time Frame: prior to the initial dose and 30min, 1h, 2h, 3h, 4h, 6h post dose ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Influence of Metoclopramide on Ticagrelor Pharmacokinetics and Pharmacodynamics in Patients With Unstable Angina Pectoris on Concomitant Treatment With Morphine
Official Title  ICMJE Differences in the Pharmacokinetic and Pharmacodynamic Profile of Ticagrelor and Its Active Metabolite AR-C124900XX Between Patients With Unstable Angina Pectoris Treated With Crushed Ticagrelor and a Combination of Morphine and Metoclopramide or Morphine Alone - a Randomized Study
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 metoclopramide 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 metoclopramide 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Unstable Angina Pectoris
Intervention  ICMJE
  • Drug: Crushed ticagrelor followed by morphine
    Crushed ticagrelor (180 mg) followed by morphine 5 mg intravenously
    Other Name: Brilique
  • Drug: Crushed ticagrelor, morphine,metoclopramide
    Crushed ticagrelor (180 mg) orally followed by morphine 5 mg and metoclopramide 10 mg intravenously
    Other Name: Brilique
Study Arms  ICMJE
  • Active Comparator: Crushed ticagrelor followed by morphine
    crushed ticagrelor 180 mg administered orally followed by morphine 5 mg intravenously
    Intervention: Drug: Crushed ticagrelor followed by morphine
  • Active Comparator: Crushed ticagrelor, morphine,metoclopramide
    crushed ticagrelor 180 mg administered orally followed by morphine 5 mg and metoclopramide 10 mg intravenously
    Intervention: Drug: Crushed ticagrelor, morphine,metoclopramide
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 28, 2019)
32
Original Estimated Enrollment  ICMJE
 (submitted: October 18, 2016)
30
Actual Study Completion Date  ICMJE December 2017
Actual Primary Completion Date December 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Poland
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02939235
Other Study ID Numbers  ICMJE CMUMK202F
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Responsible Party Jacek Kubica, Collegium Medicum w Bydgoszczy
Study Sponsor  ICMJE Collegium Medicum w Bydgoszczy
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Jacek Kubica, MD., PhD. Cardiology Department, Dr. A. Jurasz University Hospital
PRS Account Collegium Medicum w Bydgoszczy
Verification Date March 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP