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

ST-segment Elevation Myocardial Infarction Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02913469
• Other study ID #: Morphine & Ticagrelor
• Status: Recruiting
• Phase: Phase 4
• Start date: December 12, 2014
• Est. completion date: August 15, 2020

Study information

• Verified date: March 2020
• Source: General Hospital of Chinese Armed Police Forces
• Contact: huiliang liu, MD
• Phone: +8610 57976707
• Email: yueniaodream520[@]126.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 128
• Est. completion date: August 15, 2020
• Est. primary completion date: August 15, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Infarction
• Myocardial Infarction
• ST Elevation Myocardial Infarction
• ST-segment Elevation Myocardial Infarction

Intervention

Drug:
• Morphine
The patients in group A would be administrated intravenous morphine 5mg
• metoclopramide
the patients in group C would be administrated intravenous metoclopramide 10mg
• saline
the patients in group D would be administrated intravenous 0.9%normal saline 2mland 0.9%normal saline 2ml.

Locations

Country	Name	City	State
China	Cardiology Department, Chinese Armed Police Force Genral Hospital, Beijing China	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
General Hospital of Chinese Armed Police Forces

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Platelet Reactivity Index(PRI) Measured by VASP-P	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	Platelet Reactivity Index (PRI) Measured by VASP-P		0.5hour,8hours after the loading dose of ticagrelor
Secondary	the incidence of major adverse cardiovascular and cerebrovascular events		follow-up for 30 days after the loading dose of ticagrelor