Clinical trial NCT01311700: Effect of METOprolol in CARDioproteCtioN During an Acute Myocardial InfarCtion. The METOCARD-CNIC Trial.
Official title: Effect of METOprolol in CARDioproteCtioN During an Acute Myocardial InfarCtion. The ME"Effect 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Myocardial Infarction
Keywords: Ischemia
Reperfusion
Myocardial infarction
Beta blockers
Metoprolol
Acute myocardial infarction
Necrosis
Salvaged Myocardium
Lead sponsor: Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III
Sponsor class: OTHER
Collaborators: name: Ministerio de Sanidad, Servicios Sociales e Igualdad
name: Fundación Mutua Madrileña
First posted: 2011-03-09
Enrollment: 221
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Infarct size evaluated primarily by area of delayed enhancement on cardiac magnetic resonance imaging.
timeFrame: 5-7 days after reperfusion
Secondary outcomes:
measure: Infarct size evaluated primarily by the area under the curve of CK, CK-MB and troponin release over the first 72 hours of reperfusion.
timeFrame: over the first 72 hours of reperfusion.
measure: Infarct size evaluated by area of delayed enhancement on cardiac magnetic resonance imaging.
timeFrame: at month 6
measure: 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.
timeFrame: 5-7 days after reperfusion.
measure: Percent salvaged myocardium evaluated by cardiac magnetic resonance imaging.
timeFrame: 5-7 days after reperfusion
measure: Recovery of myocardial contraction assessed by magnetic resonance imaging and echocardiography.
timeFrame: at month 6
measure: Myocardial perfusion evaluated by magnetic resonance imaging.
timeFrame: 5-7 days post-reperfusion.
measure: Composite of death, malignant ventricular arrhythmias, reinfarction or admission due to heart failure
timeFrame: hospital discharge, 1, 6 and 12 months post-reperfusion.
measure: Major cardiovascular events (death, malignant ventricular arrhythmias, AV block, cardiogenic shock, reinfarction).
timeFrame: within first 24 hr post-reperfusion.
Other outcomes:
Locations:
city: Santander
country: Spain
facility: Hospital Marqués de Valdecilla
state: Cantabria
city: Majadahonda
country: Spain
facility: Hospital Puerta de Hierro
state: Madrid
city: Vigo
country: Spain
facility: Hospital Universitario de Vigo-Hospital Meixoeiro
state: Pontevedra
city: Vigo
country: Spain
facility: Servicio de Urgencias Sanitarias 061 de Galicia
state: Pontevedra
city: León
country: Spain
facility: Hospital de León
city: Madrid
country: Spain
facility: Hospital La Princesa
city: Madrid
country: Spain
facility: Servicio de Asistencia Municipal de Urgencia y Rescate (SAMUR)
city: Madrid
country: Spain
facility: • Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC),
city: Madrid
country: Spain
facility: Hospital Clínico San Carlos
city: Madrid
country: Spain
facility: Hospital 12 de Octubre
city: Madrid
country: Spain
facility: Servicio de Urgencia Médica de la Comunidad de Madrid (SUMMA) 112
city: Madrid
country: Spain
facility: Hospital Universitario Quirón
Study officials:
affiliation: CNIC
name: Borja Ibanez, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Ibanez B, Cimmino G, Prat-Gonzalez S, Vilahur G, Hutter R, Garcia MJ, Fuster V, Sanz J, Badimon L, Badimon JJ. The cardioprotection granted by metoprolol is restricted to its administration prior to coronary reperfusion. Int J Cardiol. 2011 Mar 17;147(3):428-32. doi: 10.1016/j.ijcard.2009.09.551. Epub 2009 Nov 12.
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