Effects of Morphine on Loading-dose Ticagrelor in Patients With ST-segment Elevation Myocardial Infarction

Sponsor
General Hospital of Chinese Armed Police Forces (Other)
Overall Status
Unknown status
CT.gov ID
NCT02913469
Collaborator
(none)
128
1
4
68.1
1.9

Study Details

Study Description

Brief Summary

Percutaneous coronary intervention(PCI) has become the first choice for STEMI patients.According to the current guidelines,dual antiplatelet therapy with a P2Y12 receptor inhibitor and aspirin ,and intravenous injection of morphine therapy for chest pain relief in necessity play a pivotal role in the treatment of patients with ST elevation myocardial infarction before primary percutaneous coronary intervention.And ticagrelor is recommended in patients with ST segment elevation myocardial infarction undergoing PCI, with class IB indication.Therefore coadministration of morphine and ticagrelor are commonplace.Currently, some studies have found that morphine delayed and attenuated exposure to ticagrelor,but it is not clear of the pathogenesis of it.Some researchers say that morphine results in a weaker and retarded antiplatelet effect of ticagrelor in STEMI patients before PCI by inhibition of gastrointestinal peristalsis and causing vomiting.The study is aimed at exploring whether morphine delay and attenuate exposure to ticagrelor and its antiplatelet effect.In addition, the trial will explore the possible mechanism which morphne delay and attenuate exposure to ticagrelor in patients with ST-segment elevation myocardial infarction before PCI.

Condition or Disease Intervention/Treatment Phase
Phase 4

Detailed Description

The study is a single center, randomized, single-blind, controlled trial.From September 1st, 2014 to February 10, 2016,patients with STEMI who prepared to accept PCI were screened according to the inclusion criteria. All patients for eligibility for the study received orally a 300 mg loading dose (LD) of plain aspirin and a 180mg loading dose (LD) of plain ticagrelor and then signed a written informed consent to participate in the study.Then,the patients were randomly assigned to four treatment groups.The patients in group A would be administrated intravenous morphine 5mg and metoclopramide 10mg,the patients in group B would be administrated intravenous morphine 5mg and 0.9%normal saline 2ml,the patients in group C would be administrated intravenous metoclopramide 10mg and 0.9%normal saline 2ml, the patients in group D would be administrated intravenous 0.9%normal saline 2mland 0.9%normal saline 2ml. Subsequently,all patients would received orally plain aspirin 100mg once a day and plain ticagrelor 90mg twice a day and 1 month of follow-up.The investigators would calculate the platelet response index before LD and 0.5h,2h,8h after LD by platelet vasodilator-stimulated phosphoprotein phosphorylation assay with flow cytometry instrument(BD FACS Calibur). The primary study end-point was platelet response index by PRI VASP 2 hours after LD. Secondary end-points were (1) The platelet response index by PRI VASP half an hour and 8 hours after LD.(2)Record the electrocardiogram changes(the incidence of a 70% reduction after PCI ,TIMI flow of crime vessels(TIMI flow frames),the incidence of acute/subacute thrombotic events,the incidence of major adverse cardiovascular and cerebrovascular events,the incidence of primary and secondary bleeding.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
128 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Single (Participant)
Primary Purpose:
Treatment
Official Title:
The Effects of Morphine on Loading-dose Ticagrelor in Patients With ST-segment Elevation Myocardial Infarction Before Primary Percutaneous Coronary Interven Tion
Actual Study Start Date :
Dec 12, 2014
Anticipated Primary Completion Date :
Aug 15, 2020
Anticipated Study Completion Date :
Aug 15, 2020

Arms and Interventions

Arm Intervention/Treatment
Experimental: morphine+metoclopramide

administrated intravenous morphine 5mg and metoclopramide 10mg

Drug: Morphine
The patients in group A would be administrated intravenous morphine 5mg
Other Names:
  • morphine hydrochloride
  • Drug: metoclopramide
    the patients in group C would be administrated intravenous metoclopramide 10mg
    Other Names:
  • Pasprtin
  • Active Comparator: morphine

    avenous morphine 5mg and 0.9%normal saline 2ml

    Drug: Morphine
    The patients in group A would be administrated intravenous morphine 5mg
    Other Names:
  • morphine hydrochloride
  • Drug: saline
    the patients in group D would be administrated intravenous 0.9%normal saline 2mland 0.9%normal saline 2ml.
    Other Names:
  • Physiological Saline
  • Sham Comparator: metoclopramide

    intravenous metoclopramide 10mg and 0.9%normal saline 2ml

    Drug: metoclopramide
    the patients in group C would be administrated intravenous metoclopramide 10mg
    Other Names:
  • Pasprtin
  • Drug: saline
    the patients in group D would be administrated intravenous 0.9%normal saline 2mland 0.9%normal saline 2ml.
    Other Names:
  • Physiological Saline
  • Placebo Comparator: placebo

    intravenous 0.9%normal saline 2mland 0.9%normal saline 2ml

    Drug: saline
    the patients in group D would be administrated intravenous 0.9%normal saline 2mland 0.9%normal saline 2ml.
    Other Names:
  • Physiological Saline
  • Outcome Measures

    Primary Outcome Measures

    1. Platelet Reactivity Index(PRI) Measured by VASP-P [2 hours after the loading dose of ticagrelor]

      Vasodilator-stimulated phosphoprotein(VASP) phosphorylation, a measure of P2Y12 receptor reactivity, was determined by flow cytometry with the use of the Platelet VASP-FCM Kit (Stago, France)and recorded as the platelet reactivity index

    Secondary Outcome Measures

    1. Platelet Reactivity Index (PRI) Measured by VASP-P [0.5hour,8hours after the loading dose of ticagrelor]

    2. the incidence of major adverse cardiovascular and cerebrovascular events [follow-up for 30 days after the loading dose of ticagrelor]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 80 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    1. Provision of informed consent prior to any study-specific procedures

    2. Male or female aged from 18 to 80 years old

    3. Patients with STEMI scheduled to undergo PCI.

    Exclusion Criteria:
    1. Hypersensitivity to the active substance or to any of the excipients

    2. Active bleeding or bleeding diathesis

    3. Previous transient ischemic attack

    4. Antiplatelet (clopidogrel, prasugrel, ticagrelor) administration in the week before the index event

    5. Known relevant hematological conditions

    6. Left ventricular ejection fraction ≤ 30%

    7. Renal failure with creatinine ≥ 3 mg/dl

    8. History of liver disease

    9. Increased risk of bradycardia

    10. Concomitant therapy with drugs known to interfere with CYP3A4 metabolism.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Cardiology Department, Chinese Armed Police Force Genral Hospital, Beijing China Beijing China 100039

    Sponsors and Collaborators

    • General Hospital of Chinese Armed Police Forces

    Investigators

    • Study Chair: huiliang liu, MD, CHINESE ARMED POLICE FORCE GENRAL HOSPITAL

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    General Hospital of Chinese Armed Police Forces
    ClinicalTrials.gov Identifier:
    NCT02913469
    Other Study ID Numbers:
    • Morphine & Ticagrelor
    First Posted:
    Sep 23, 2016
    Last Update Posted:
    Mar 31, 2020
    Last Verified:
    Mar 1, 2020
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Keywords provided by General Hospital of Chinese Armed Police Forces
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Mar 31, 2020