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

Myocardial Infarction Clinical Trial

— METOCARD-CNIC  

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01311700
• Other study ID #: METOCARD-CNIC
• Secondary ID: CNIC translation
• Status: Completed
• Phase: Phase 4
• Start date: November 2010
• Est. completion date: October 2017

Study information

• Verified date: December 2017
• Source: Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 221
• Est. completion date: October 2017
• Est. primary completion date: October 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Infarction
• Myocardial Infarction

Intervention

Drug:
• Injectable (i.v.) metoprolol tartrate (up to 15 mg).
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.

Locations

Country	Name	City	State
Spain	Hospital de León	León
Spain	• Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC),	Madrid
Spain	Hospital 12 de Octubre	Madrid
Spain	Hospital Clínico San Carlos	Madrid
Spain	Hospital La Princesa	Madrid
Spain	Hospital Universitario Quirón	Madrid
Spain	Servicio de Asistencia Municipal de Urgencia y Rescate (SAMUR)	Madrid
Spain	Servicio de Urgencia Médica de la Comunidad de Madrid (SUMMA) 112	Madrid
Spain	Hospital Puerta de Hierro	Majadahonda	Madrid
Spain	Hospital Marqués de Valdecilla	Santander	Cantabria
Spain	Hospital Universitario de Vigo-Hospital Meixoeiro	Vigo	Pontevedra
Spain	Servicio de Urgencias Sanitarias 061 de Galicia	Vigo	Pontevedra

Sponsors (3)

Lead Sponsor	Collaborator
Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III	Fundación Mutua Madrileña, Ministerio de Sanidad, Servicios Sociales e Igualdad

Country where clinical trial is conducted

Spain, 

References & Publications (8)

Halkin A, Grines CL, Cox DA, Garcia E, Mehran R, Tcheng JE, Griffin JJ, Guagliumi G, Brodie B, Turco M, Rutherford BD, Aymong E, Lansky AJ, Stone GW. Impact of intravenous beta-blockade before primary angioplasty on survival in patients undergoing mechanical reperfusion therapy for acute myocardial infarction. J Am Coll Cardiol. 2004 May 19;43(10):1780-7. — View Citation

Harjai KJ, Stone GW, Boura J, Grines L, Garcia E, Brodie B, Cox D, O'Neill WW, Grines C. Effects of prior beta-blocker therapy on clinical outcomes after primary coronary angioplasty for acute myocardial infarction. Am J Cardiol. 2003 Mar 15;91(6):655-60. — View Citation

Ibanez B, Cimmino G, Prat-González S, Vilahur G, Hutter R, García 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. — View Citation

Ibanez B, Fuster V, Macaya C, Sánchez-Brunete V, Pizarro G, López-Romero P, Mateos A, Jiménez-Borreguero J, Fernández-Ortiz A, Sanz G, Fernández-Friera L, Corral E, Barreiro MV, Ruiz-Mateos B, Goicolea J, Hernández-Antolín R, Acebal C, García-Rubira JC, Albarrán A, Zamorano JL, Casado I, Valenciano J, Fernández-Vázquez F, de la Torre JM, Pérez de Prado A, Iglesias-Vázquez JA, Martínez-Tenorio P, Iñiguez A. Study design for the "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 infarction. Am Heart J. 2012 Oct;164(4):473-480.e5. doi: 10.1016/j.ahj.2012.07.020. — View Citation

Ibanez B, Prat-González S, Speidl WS, Vilahur G, Pinero A, Cimmino G, García MJ, Fuster V, Sanz J, Badimon JJ. Early metoprolol administration before coronary reperfusion results in increased myocardial salvage: analysis of ischemic myocardium at risk using cardiac magnetic resonance. Circulation. 2007 Jun 12;115(23):2909-16. Epub 2007 May 21. — View Citation

Larose E, Rodés-Cabau J, Pibarot P, Rinfret S, Proulx G, Nguyen CM, Déry JP, Gleeton O, Roy L, Noël B, Barbeau G, Rouleau J, Boudreault JR, Amyot M, De Larochellière R, Bertrand OF. Predicting late myocardial recovery and outcomes in the early hours of ST-segment elevation myocardial infarction traditional measures compared with microvascular obstruction, salvaged myocardium, and necrosis characteristics by cardiovascular magnetic resonance. J Am Coll Cardiol. 2010 Jun 1;55(22):2459-69. doi: 10.1016/j.jacc.2010.02.033. — View Citation

Raman SV, Simonetti OP, Winner MW 3rd, Dickerson JA, He X, Mazzaferri EL Jr, Ambrosio G. Cardiac magnetic resonance with edema imaging identifies myocardium at risk and predicts worse outcome in patients with non-ST-segment elevation acute coronary syndrome. J Am Coll Cardiol. 2010 Jun 1;55(22):2480-8. doi: 10.1016/j.jacc.2010.01.047. — View Citation

Sharma SK, Kini A, Marmur JD, Fuster V. Cardioprotective effect of prior beta-blocker therapy in reducing creatine kinase-MB elevation after coronary intervention: benefit is extended to improvement in intermediate-term survival. Circulation. 2000 Jul 11;102(2):166-72. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Infarct size evaluated primarily by area of delayed enhancement on cardiac magnetic resonance imaging.		5-7 days after reperfusion
Secondary	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.
Secondary	Infarct size evaluated by area of delayed enhancement on cardiac magnetic resonance imaging.		at month 6
Secondary	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.
Secondary	Percent salvaged myocardium evaluated by cardiac magnetic resonance imaging.		5-7 days after reperfusion
Secondary	Recovery of myocardial contraction assessed by magnetic resonance imaging and echocardiography.		at month 6
Secondary	Myocardial perfusion evaluated by magnetic resonance imaging.		5-7 days post-reperfusion.
Secondary	Composite of death, malignant ventricular arrhythmias, reinfarction or admission due to heart failure		hospital discharge, 1, 6 and 12 months post-reperfusion.
Secondary	Major cardiovascular events (death, malignant ventricular arrhythmias, AV block, cardiogenic shock, reinfarction).		within first 24 hr post-reperfusion.

External Links

•   Link
•   Official Study Website