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

Phase 4

Completed

• Conditions: Myocardial Infarction
• Interventions: Drug: Injectable (i.v.) metoprolol tartrate (up to 15 mg).

• Registration Number: NCT01311700
• Lead Sponsor: Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III

Brief Summary

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

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.

Study Timeline

• Study Start: 2010-11
• Study First Submitted: 2011-03-08
• Study First Submitted QC: 2011-03-08
• Study First Posted: 2011-03-09
• Primary Completion: 2012-10
• Study Completion: 2017-10
• Status Verified: 2017-12
• Last Update Submitted: 2018-06-15
• Last Update Posted: 2018-06-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 221

Inclusion Criteria

1. Confirmed* acute anterior wall myocardial infarction (ST segment elevation ≥ 2mm in ≥ 2 contiguous leads [one of which should be V2, V3, or V4]).

2. 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

1. COPD or asthma on active bronchodilator therapy
2. Active treatment with beta blockers
3. Left bundle branch block or pacemaker.
4. Systolic blood pressure <120 mmHg, Heart rate <60 bpm, or AV block (PR˃240 mS or superior) on diagnosis.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Early metoprolol initiation strategy	Injectable (i.v.) metoprolol tartrate (up to 15 mg).	-

Primary Outcome Measures

Name	Time	Method
Infarct size evaluated primarily by area of delayed enhancement on cardiac magnetic resonance imaging.	5-7 days after reperfusion

Secondary Outcome Measures

Name	Time	Method
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 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
Myocardial perfusion evaluated by magnetic resonance imaging.	5-7 days post-reperfusion.
Infarct size evaluated by area of delayed enhancement on cardiac magnetic resonance imaging.	at month 6
Recovery of myocardial contraction assessed by magnetic resonance imaging and echocardiography.	at month 6
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.

Trial Locations

Locations (12)

Hospital Universitario de Vigo-Hospital Meixoeiro; 🇪🇸 Vigo, Pontevedra, Spain

Hospital Puerta de Hierro; 🇪🇸 Majadahonda, Madrid, Spain

Hospital de León; 🇪🇸 León, Spain

Hospital La Princesa; 🇪🇸 Madrid, Spain

Hospital Marqués de Valdecilla; 🇪🇸 Santander, Cantabria, Spain

Servicio de Urgencias Sanitarias 061 de Galicia; 🇪🇸 Vigo, Pontevedra, Spain

Servicio de Asistencia Municipal de Urgencia y Rescate (SAMUR); 🇪🇸 Madrid, Spain

• Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC),; 🇪🇸 Madrid, Spain

Hospital 12 de Octubre; 🇪🇸 Madrid, Spain

Hospital Clínico San Carlos; 🇪🇸 Madrid, Spain

Servicio de Urgencia Médica de la Comunidad de Madrid (SUMMA) 112; 🇪🇸 Madrid, Spain

Hospital Universitario Quirón; 🇪🇸 Madrid, Spain