Effect of Intravenous Metoprolol Combining RIC on Myocardial Protection in STEMI Patients

Study Overview
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Brief Summary
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The main purpose of this study is to compare the myocardial protection effect of intravenous metoprolol combined with remote ischemic conditioning (RIC) and single treatment before reperfusion in Chinese patients with anterior STEMI. This study sought to find possible strategies to further improve myocardial protection in Chinese patients with anterior STEMI.

Detailed Description
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This study is a prospective, multi-center, randomized controlled study. It is planned to enroll 1200 patients with anterior STEMI. Immediately after the first medical contact, the patients who were determined by the investigator to meet the inclusion/exclusion criteria were randomized through the interactive web response system (IWRS) and received different pre-reperfusion treatments. The four groups were placebo group, metoprolol group, remote ischemic conditioning (RIC) group and metoprolol & RIC group. Subsequently, the investigator conduct diagnosis and treatment according to the patient's specific conditions and check the serum level of myocardial damage markers (i.e. CK and CK-MB) at the time of admission, 12, 24, 36, 48, 60 hours, respectively. If the patient undergoes PCI treatment, additional detection of myocardial damage markers immediately after PCI is also required. All patients were followed for 1 year with an office visit or a telephone call at 1, 3, 6, 9 and 12 months to evaluate the health status and adverse clinical events of patients.

Official Title
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Combined Metoprolol and Remote Ischemic Conditioning in Cardioprotection of Anterior ST-segment Elevation Myocardial Infarction (METRICATION)

Conditions
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Anterior Myocardial Infarction, Heart Failure

Intervention / Treatment
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* Drug: intravenous Placebo
* Drug: Metoprolol Injectable Product
* Device: Romote Ischemic Conditioning (RIC)
* Combination Product: Metoprolol & RIC


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ages 18 to 80 years; presenting within 12 h of symptoms onset, with anterior STEMI and planned for pPCI; anterior STEMI was defined as the occurrence of >20 min of chest pain and ST-segment elevation (>2 mm) in at least 2 contiguous precordial leads; sign informed consent; Exclusion Criteria: systolic blood pressure < 110mmHg; cardiogenic shock or with heart failure symptoms, Killip III IV; allergic history of metoprolol; history of asthma or the need for bronchodilators; PR interval > 240ms, II III atrioventricular block； heart rate < 60 beats/min; unable to consent; pregnancy and lactation women; life expectancy for diseases (i.e. cancer) < 1 year.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo group<br>Patients receive intravenous placebo injection. | Drug: intravenous Placebo<br>* Patients receive intravenous Placebo (saline) injection<br>|
| Experimental: Intravenous metoprolol group<br>Patients receive intravenous metoprolol injection. | Drug: Metoprolol Injectable Product<br>* Patients receive intravenous Metoprolol injection<br>|
| Experimental: RIC group<br>Patients receive RIC treatment. | Device: Romote Ischemic Conditioning (RIC)<br>* Patients receive RIC treatment<br>|
| Experimental: Intravenous metoprolol and RIC group<br>Patients receive intravenous metoprolol injection and RIC treatment. | Combination Product: Metoprolol & RIC<br>* Patients receive Metoprolol & RIC treatment<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Myocardial infarct size | Estimating myocardial infarct size by area under CK, CK-MB curve | 60 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Major adverse cardiac and cerebrovascular events (MACCE) | Composition of death, heart failure, reinfarction, revascularization, malignant ventricular arrhythmias, stroke) | 1 year | 
| Incidence of heart failure | Incidence of heart failure | 1 year | 
| myocardial infarct size measured by MRI (optional) | myocardial infarct size measured by MRI (optional) | 7 days after AMI | 
| Safety endpoint: incidence of severe bradycardia or hypotension | Severe bradycardia (heart rate <40bpm) or hypotension (systolic blood pressure <80mmHg) | 24 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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RIC, Anterior Myocardial Infarction, Intravenous Metoprolol, Myocardial Protection