search
Back to results

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

Primary Purpose

Unstable Angina Pectoris

Status
Completed
Phase
Phase 4
Locations
Poland
Study Type
Interventional
Intervention
Crushed ticagrelor followed by morphine
Crushed ticagrelor, morphine,metoclopramide
Sponsored by
Collegium Medicum w Bydgoszczy
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Unstable Angina Pectoris

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

  • Cardiology Department, Dr. A. Jurasz University Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

Crushed ticagrelor followed by morphine

Crushed ticagrelor, morphine,metoclopramide

Arm Description

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

crushed ticagrelor 180 mg administered orally followed by morphine 5 mg and metoclopramide 10 mg intravenously

Outcomes

Primary Outcome Measures

Time to maximum concentration (tmax) for ticagrelor and AR-C124900XX for ticagrelor+morphine vs ticagrelor+morphine+metoclopramide arms

Secondary Outcome Measures

Maximum ticagrelor and AR-C124900XX concentration at 6h after administration (Cmax6)
Area under the plasma concentration-time curve for ticagrelor (AUC 0-6h)
Area under the plasma concentration-time curve for AR-C124900XX (AUC 0-6h)
Platelet arbitrary aggregation units/min assessed by Multiple Electrode Aggregometry

Full Information

First Posted
October 18, 2016
Last Updated
March 28, 2019
Sponsor
Collegium Medicum w Bydgoszczy
search

1. Study Identification

Unique Protocol Identification Number
NCT02939235
Brief Title
Influence of Metoclopramide on Ticagrelor Pharmacokinetics and Pharmacodynamics in Patients With Unstable Angina Pectoris on Concomitant Treatment With Morphine
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
March 2019
Overall Recruitment Status
Completed
Study Start Date
July 2016 (undefined)
Primary Completion Date
December 2017 (Actual)
Study Completion Date
December 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Collegium Medicum w Bydgoszczy

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Unstable Angina Pectoris

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
32 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Crushed ticagrelor followed by morphine
Arm Type
Active Comparator
Arm Description
crushed ticagrelor 180 mg administered orally followed by morphine 5 mg intravenously
Arm Title
Crushed ticagrelor, morphine,metoclopramide
Arm Type
Active Comparator
Arm Description
crushed ticagrelor 180 mg administered orally followed by morphine 5 mg and metoclopramide 10 mg intravenously
Intervention Type
Drug
Intervention Name(s)
Crushed ticagrelor followed by morphine
Other Intervention Name(s)
Brilique
Intervention Description
Crushed ticagrelor (180 mg) followed by morphine 5 mg intravenously
Intervention Type
Drug
Intervention Name(s)
Crushed ticagrelor, morphine,metoclopramide
Other Intervention Name(s)
Brilique
Intervention Description
Crushed ticagrelor (180 mg) orally followed by morphine 5 mg and metoclopramide 10 mg intravenously
Primary Outcome Measure Information:
Title
Time to maximum concentration (tmax) for ticagrelor and AR-C124900XX for ticagrelor+morphine vs ticagrelor+morphine+metoclopramide arms
Time Frame
6 hours
Secondary Outcome Measure Information:
Title
Maximum ticagrelor and AR-C124900XX concentration at 6h after administration (Cmax6)
Time Frame
6 hours
Title
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
Title
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
Title
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jacek Kubica, MD., PhD.
Organizational Affiliation
Cardiology Department, Dr. A. Jurasz University Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Cardiology Department, Dr. A. Jurasz University Hospital
City
Bydgoszcz
State/Province
Kujawsko-Pomorskie
ZIP/Postal Code
85-094
Country
Poland

12. IPD Sharing Statement

Plan to Share IPD
Yes

Learn more about this trial

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

We'll reach out to this number within 24 hrs