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

March 29, 2020 updated by: General Hospital of Chinese Armed Police Forces

The Effects of Morphine on Loading-dose Ticagrelor in Patients With ST-segment Elevation Myocardial Infarction Before Primary Percutaneous Coronary Interven Tion

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Anticipated)

128

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
      • Beijing, China, 100039
        • Recruiting
        • Cardiology Department, Chinese Armed Police Force Genral Hospital, Beijing China
        • Contact:
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Platelet Reactivity Index(PRI) Measured by VASP-P
Time Frame: 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
2 hours after the loading dose of ticagrelor

Secondary Outcome Measures

Outcome Measure
Time Frame
Platelet Reactivity Index (PRI) Measured by VASP-P
Time Frame: 0.5hour,8hours after the loading dose of ticagrelor
0.5hour,8hours after the loading dose of ticagrelor
the incidence of major adverse cardiovascular and cerebrovascular events
Time Frame: follow-up for 30 days after the loading dose of ticagrelor
follow-up for 30 days after the loading dose of ticagrelor

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

General Hospital of Chinese Armed Police Forces

Investigators

  • Study Chair: HUILIANG LIU, MD, CHINESE ARMED POLICE FORCE GENRAL HOSPITAL

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 12, 2014

Primary Completion (Anticipated)

August 15, 2020

Study Completion (Anticipated)

August 15, 2020

Study Registration Dates

First Submitted

September 9, 2016

First Submitted That Met QC Criteria

September 22, 2016

First Posted (Estimate)

September 23, 2016

Study Record Updates

Last Update Posted (Actual)

March 31, 2020

Last Update Submitted That Met QC Criteria

March 29, 2020

Last Verified

March 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Morphine & Ticagrelor

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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