Effect of METOprolol in CARDioproteCtioN During an Acute Myocardial InfarCtion. The METOCARD-CNIC Trial.

Study Overview
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Brief Summary
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The purpose of this study is to test whether early pre-reperfusion metoprolol administration in patients suffering and acute myocardial infarction might reduce the size of myocardial necrosis.

Detailed Description
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Acute myocardial infarction (AMI) is a chief cause of death worldwide. The best strategy to limit myocardial damage is to perform an early coronary reperfusion. However, despite reperfusion, the size of infarctions is many times large. Infarct size has been recently shown to be a strong predictor of future cardiovascular events and mortality. Therefore interventions aimed at reducing infarct size are the matter of intense research; but despite great efforts, no therapy has been shown to consistently limit infarct size. ß-blockers are a class of drugs that have been used to treat cardiovascular conditions for several decades. β-blockers reduce mortality when administered after an AMI, and are a class IA indication in this context. What remains unclear is what timing and route of β-blocker administration gives the maximum cardioprotective effect. In particular, whether early β-blocker administration is able to reduce infarct size is a subject of debate. Recent experimental data suggest that the β1 selective blocker metoprolol is able to limit the area of necrosis only when administered before reperfusion. The objective of this trial is to determine whether the administration of intravenous pre-reperfusion metoprolol might reduce infarct size.

Official Title
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Effect of METOprolol in CARDioproteCtioN During an Acute Myocardial InfarCtion. The MEEffect of METOprolol in CARDioproteCtioN During an Acute Myocardial InfarCtion (METOCARD-CNIC): A Randomized, Controlled Parallel-group, Observer-blinded Clinical Trial of Early Pre-reperfusion Metoprolol Administration in ST-segment Elevation Myocardial infarctionTOCARD-CNIC Trial.

Conditions
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Myocardial Infarction

Intervention / Treatment
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* Drug: Injectable (i.v.) metoprolol tartrate (up to 15 mg).


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmed* acute anterior wall myocardial infarction (ST segment elevation ≥ 2mm in ≥ 2 contiguous leads [one of which should be V2, V3, or V4]). Killip class I or II on diagnosis. Cases of non-confirmed infarction by enzymatic release (above 2 standard deviations from upper limit of CK and Troponin) are excluded from efficacy analysis but kept in the safety analysis. Exclusion Criteria: COPD or asthma on active bronchodilator therapy Active treatment with beta blockers Left bundle branch block or pacemaker. Systolic blood pressure <120 mmHg, Heart rate <60 bpm, or AV block (PR˃240 mS or superior) on diagnosis.

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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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Early metoprolol initiation strategy<br> | Drug: Injectable (i.v.) metoprolol tartrate (up to 15 mg).<br>* Patients are randomized to active intervention (early metoprolol initiation strategy) or no treatment (delayed metoprolol initiation strategy). Patients randomized to early metoprolol initiation strategy receive up to three 5mg i.v. dosages (2 minutes apart) before reperfusion. Patients randomized to delayed metoprolol initiation strategy receive no active treatment before reperfusion. Patients in both groups receive oral metoprolol tartrate treatment (25-100mg/12h), starting 12-24 hr post-reperfusion.<br>|
| No Intervention: Delayed metoprolol initiation strategy<br> | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Infarct size evaluated primarily by area of delayed enhancement on cardiac magnetic resonance imaging. |  | 5-7 days after reperfusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Infarct size evaluated primarily by the area under the curve of CK, CK-MB and troponin release over the first 72 hours of reperfusion. |  | over the first 72 hours of reperfusion. | 
| Infarct size evaluated by area of delayed enhancement on cardiac magnetic resonance imaging. |  | at month 6 | 
| Infarct size evaluated by area of delayed enhancement on cardiac magnetic resonance imaging in patients with coronary TIMI flow 0-1 of culprit coronary artery. |  | 5-7 days after reperfusion. | 
| Percent salvaged myocardium evaluated by cardiac magnetic resonance imaging. |  | 5-7 days after reperfusion | 
| Recovery of myocardial contraction assessed by magnetic resonance imaging and echocardiography. |  | at month 6 | 
| Myocardial perfusion evaluated by magnetic resonance imaging. |  | 5-7 days post-reperfusion. | 
| Composite of death, malignant ventricular arrhythmias, reinfarction or admission due to heart failure |  | hospital discharge, 1, 6 and 12 months post-reperfusion. | 
| Major cardiovascular events (death, malignant ventricular arrhythmias, AV block, cardiogenic shock, reinfarction). |  | within first 24 hr post-reperfusion. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ischemia, Reperfusion, Myocardial infarction, Beta blockers, Metoprolol, Acute myocardial infarction, Necrosis, Salvaged Myocardium