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

NCT ID: NCT01311700

Last Updated: 2018-06-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

221 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-11-30

Study Completion Date

2017-10-31

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.

Conditions

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Myocardial Infarction

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors

Study Groups

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Early metoprolol initiation strategy

Group Type ACTIVE_COMPARATOR

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

Intervention Type DRUG

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.

Delayed metoprolol initiation strategy

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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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.

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Ministerio de Sanidad, Servicios Sociales e Igualdad

OTHER_GOV

Sponsor Role collaborator

Fundación Mutua Madrileña

OTHER

Sponsor Role collaborator

Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Borja Ibanez, MD PhD

Role: PRINCIPAL_INVESTIGATOR

CNIC

Locations

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Hospital Marqués de Valdecilla

Santander, Cantabria, Spain

Site Status

Hospital Puerta de Hierro

Majadahonda, Madrid, Spain

Site Status

Hospital Universitario de Vigo-Hospital Meixoeiro

Vigo, Pontevedra, Spain

Site Status

Servicio de Urgencias Sanitarias 061 de Galicia

Vigo, Pontevedra, Spain

Site Status

Hospital de León

León, , Spain

Site Status

Hospital La Princesa

Madrid, , Spain

Site Status

Servicio de Asistencia Municipal de Urgencia y Rescate (SAMUR)

Madrid, , Spain

Site Status

• Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC),

Madrid, , Spain

Site Status

Hospital Clínico San Carlos

Madrid, , Spain

Site Status

Hospital 12 de Octubre

Madrid, , Spain

Site Status

Servicio de Urgencia Médica de la Comunidad de Madrid (SUMMA) 112

Madrid, , Spain

Site Status

Hospital Universitario Quirón

Madrid, , Spain

Site Status

Countries

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Spain

References

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Ibanez B, Prat-Gonzalez S, Speidl WS, Vilahur G, Pinero A, Cimmino G, Garcia 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. doi: 10.1161/CIRCULATIONAHA.106.679639. Epub 2007 May 21.

Reference Type BACKGROUND
PMID: 17515460 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19913314 (View on PubMed)

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. doi: 10.1161/01.cir.102.2.166.

Reference Type BACKGROUND
PMID: 10889126 (View on PubMed)

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. doi: 10.1016/j.jacc.2003.10.068.

Reference Type BACKGROUND
PMID: 15145099 (View on PubMed)

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. doi: 10.1016/s0002-9149(02)03401-x.

Reference Type BACKGROUND
PMID: 12633793 (View on PubMed)

Larose E, Rodes-Cabau J, Pibarot P, Rinfret S, Proulx G, Nguyen CM, Dery JP, Gleeton O, Roy L, Noel B, Barbeau G, Rouleau J, Boudreault JR, Amyot M, De Larochelliere 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.

Reference Type BACKGROUND
PMID: 20510213 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20510215 (View on PubMed)

Ibanez B, Fuster V, Macaya C, Sanchez-Brunete V, Pizarro G, Lopez-Romero P, Mateos A, Jimenez-Borreguero J, Fernandez-Ortiz A, Sanz G, Fernandez-Friera L, Corral E, Barreiro MV, Ruiz-Mateos B, Goicolea J, Hernandez-Antolin R, Acebal C, Garcia-Rubira JC, Albarran A, Zamorano JL, Casado I, Valenciano J, Fernandez-Vazquez F, de la Torre JM, Perez de Prado A, Iglesias-Vazquez JA, Martinez-Tenorio P, Iniguez 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.

Reference Type BACKGROUND
PMID: 23067904 (View on PubMed)

Lorca R, Jimenez-Blanco M, Garcia-Ruiz JM, Pizarro G, Fernandez-Jimenez R, Garcia-Alvarez A, Fernandez-Friera L, Lobo-Gonzalez M, Fuster V, Rossello X, Ibanez B. Coexistence of transmural and lateral wavefront progression of myocardial infarction in the human heart. Rev Esp Cardiol (Engl Ed). 2021 Oct;74(10):870-877. doi: 10.1016/j.rec.2020.07.007. Epub 2020 Aug 24. English, Spanish.

Reference Type DERIVED
PMID: 32855096 (View on PubMed)

Podlesnikar T, Pizarro G, Fernandez-Jimenez R, Montero-Cabezas JM, Greif N, Sanchez-Gonzalez J, Bucciarelli-Ducci C, Marsan NA, Fras Z, Bax JJ, Fuster V, Ibanez B, Delgado V. Left ventricular functional recovery of infarcted and remote myocardium after ST-segment elevation myocardial infarction (METOCARD-CNIC randomized clinical trial substudy). J Cardiovasc Magn Reson. 2020 Jun 11;22(1):44. doi: 10.1186/s12968-020-00638-8.

Reference Type DERIVED
PMID: 32522198 (View on PubMed)

Podlesnikar T, Pizarro G, Fernandez-Jimenez R, Montero-Cabezas JM, Sanchez-Gonzalez J, Bucciarelli-Ducci C, Ajmone Marsan N, Fras Z, Bax JJ, Fuster V, Ibanez B, Delgado V. Effect of Early Metoprolol During ST-Segment Elevation Myocardial Infarction on Left Ventricular Strain: Feature-Tracking Cardiovascular Magnetic Resonance Substudy From the METOCARD-CNIC Trial. JACC Cardiovasc Imaging. 2019 Jul;12(7 Pt 1):1188-1198. doi: 10.1016/j.jcmg.2018.07.019. Epub 2018 Sep 12.

Reference Type DERIVED
PMID: 30219400 (View on PubMed)

Sala-Vila A, Fernandez-Jimenez R, Pizarro G, Calvo C, Garcia-Ruiz JM, Fernandez-Friera L, Rodriguez MD, Escalera N, Palazuelos J, Macias A, Perez-Asenjo B, Fernandez-Ortiz A, Ros E, Fuster V, Ibanez B. Nutritional preconditioning by marine omega-3 fatty acids in patients with ST-segment elevation myocardial infarction: A METOCARD-CNIC trial substudy. Int J Cardiol. 2017 Feb 1;228:828-833. doi: 10.1016/j.ijcard.2016.11.214. Epub 2016 Nov 9.

Reference Type DERIVED
PMID: 27888762 (View on PubMed)

Mateos A, Garcia-Lunar I, Garcia-Ruiz JM, Pizarro G, Fernandez-Jimenez R, Huertas P, Garcia-Alvarez A, Fernandez-Friera L, Bravo J, Flores-Arias J, Barreiro MV, Chayan-Zas L, Corral E, Fuster V, Sanchez-Brunete V, Ibanez B; METOCARD-CNIC Investigators. Efficacy and safety of out-of-hospital intravenous metoprolol administration in anterior ST-segment elevation acute myocardial infarction: insights from the METOCARD-CNIC trial. Ann Emerg Med. 2015 Mar;65(3):318-24. doi: 10.1016/j.annemergmed.2014.07.010. Epub 2014 Aug 14.

Reference Type DERIVED
PMID: 25129820 (View on PubMed)

Pizarro G, Fernandez-Friera L, Fuster V, Fernandez-Jimenez R, Garcia-Ruiz JM, Garcia-Alvarez A, Mateos A, Barreiro MV, Escalera N, Rodriguez MD, de Miguel A, Garcia-Lunar I, Parra-Fuertes JJ, Sanchez-Gonzalez J, Pardillos L, Nieto B, Jimenez A, Abejon R, Bastante T, Martinez de Vega V, Cabrera JA, Lopez-Melgar B, Guzman G, Garcia-Prieto J, Mirelis JG, Zamorano JL, Albarran A, Goicolea J, Escaned J, Pocock S, Iniguez A, Fernandez-Ortiz A, Sanchez-Brunete V, Macaya C, Ibanez B. Long-term benefit of early pre-reperfusion metoprolol administration in patients with acute myocardial infarction: results from the METOCARD-CNIC trial (Effect of Metoprolol in Cardioprotection During an Acute Myocardial Infarction). J Am Coll Cardiol. 2014 Jun 10;63(22):2356-62. doi: 10.1016/j.jacc.2014.03.014. Epub 2014 Mar 30.

Reference Type DERIVED
PMID: 24694530 (View on PubMed)

Ibanez B, Macaya C, Sanchez-Brunete V, Pizarro G, Fernandez-Friera L, Mateos A, Fernandez-Ortiz A, Garcia-Ruiz JM, Garcia-Alvarez A, Iniguez A, Jimenez-Borreguero J, Lopez-Romero P, Fernandez-Jimenez R, Goicolea J, Ruiz-Mateos B, Bastante T, Arias M, Iglesias-Vazquez JA, Rodriguez MD, Escalera N, Acebal C, Cabrera JA, Valenciano J, Perez de Prado A, Fernandez-Campos MJ, Casado I, Garcia-Rubira JC, Garcia-Prieto J, Sanz-Rosa D, Cuellas C, Hernandez-Antolin R, Albarran A, Fernandez-Vazquez F, de la Torre-Hernandez JM, Pocock S, Sanz G, Fuster V. Effect of early metoprolol on infarct size in ST-segment-elevation myocardial infarction patients undergoing primary percutaneous coronary intervention: the Effect of Metoprolol in Cardioprotection During an Acute Myocardial Infarction (METOCARD-CNIC) trial. Circulation. 2013 Oct 1;128(14):1495-503. doi: 10.1161/CIRCULATIONAHA.113.003653. Epub 2013 Sep 3.

Reference Type DERIVED
PMID: 24002794 (View on PubMed)

Related Links

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Other Identifiers

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CNIC translational Grant 2009

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

2010-019939-35

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

Ministerio de Sanidad

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

METOCARD-CNIC

Identifier Type: -

Identifier Source: org_study_id

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