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Myocardial InfarctionPhase 4METOCARD-CNICNCT01311700

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

A Phase 4 study testing Injectable (i.v.) metoprolol tartrate (up to 15 mg). in people with Myocardial Infarction, run by Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III at 12 sites in Spain.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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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. Read more about this study

Who is it for?
Ages 18 to 80 years
Conditions the study is for
Myocardial Infarction
What is being tested?
Injectable (i.v.) metoprolol tartrate (up to 15 mg).
Could I receive a placebo?
No, everyone receives an active treatment
How many people
221 participants
Where
12 sitesSpain
Study dates
Nov 2010to Oct 2017
Phase
Phase 4
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.

Trial locations and contacts

12 sites in 1 country.

12 sites in 1 country

Spain12 sites

  • Hospital de León

    León, 24008

  • Hospital La Princesa

    Madrid, 28006

  • Servicio de Asistencia Municipal de Urgencia y Rescate (SAMUR)

    Madrid, 28011

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

    Madrid, 28029

  • Hospital Clínico San Carlos

    Madrid, 28040

  • Hospital 12 de Octubre

    Madrid, 28041

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

    Madrid, 28045

  • Hospital Universitario Quirón

    Madrid, 28223

  • Hospital Puerta de Hierro

    Majadahonda, Madrid, 28013

  • Hospital Marqués de Valdecilla

    Santander, Cantabria, 39008

  • Hospital Universitario de Vigo-Hospital Meixoeiro

    Vigo, Pontevedra, 36200

  • Servicio de Urgencias Sanitarias 061 de Galicia

    Vigo, Pontevedra, 36204

Other trials in Spain

About this study

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.

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.

Read the 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.

Being tested
Injectable (i.v.) metoprolol tartrate (up to 15 mg).
Keywords
Ischemia, Reperfusion, Myocardial infarction, Beta blockers, Metoprolol, Acute myocardial infarction, Necrosis, Salvaged Myocardium
Medical subject headings
Myocardial Infarction, Ischemia, Necrosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

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

Study groups in NCT01311700
Study groupRoleWhat they receive
Early metoprolol initiation strategyActive comparatorNot described
Receives: Drug: Injectable (i.v.) metoprolol tartrate (up to 15 mg).
Delayed metoprolol initiation strategyNo interventionNot described

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Infarct size evaluated primarily by area of delayed enhancement on cardiac magnetic resonance imaging.

    Measured: 5-7 days after reperfusion

Secondary outcomes (8)

  1. Infarct size evaluated primarily by the area under the curve of CK, CK-MB and troponin release over the first 72 hours of reperfusion.

    Measured: over the first 72 hours of reperfusion.

  2. Infarct size evaluated by area of delayed enhancement on cardiac magnetic resonance imaging.

    Measured: at month 6

  3. 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.

    Measured: 5-7 days after reperfusion.

  4. Percent salvaged myocardium evaluated by cardiac magnetic resonance imaging.

    Measured: 5-7 days after reperfusion

  5. Recovery of myocardial contraction assessed by magnetic resonance imaging and echocardiography.

    Measured: at month 6

  6. Myocardial perfusion evaluated by magnetic resonance imaging.

    Measured: 5-7 days post-reperfusion.

  7. Composite of death, malignant ventricular arrhythmias, reinfarction or admission due to heart failure

    Measured: hospital discharge, 1, 6 and 12 months post-reperfusion.

  8. Major cardiovascular events (death, malignant ventricular arrhythmias, AV block, cardiogenic shock, reinfarction).

    Measured: within first 24 hr post-reperfusion.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Mar 2011 (estimated)
  2. Study startNov 2010
  3. Primary completionOct 2012
  4. Study completionOct 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Single blind
Who is masked
Outcomes assessor
Enrolment
221 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01311700
Sponsor's protocol ID
METOCARD-CNIC
Other IDs
CNIC translational Grant 2009, 2010-019939-35, Ministerio de Sanidad
Acronym
METOCARD-CNIC
Status last verified
Dec 2017
First submitted
8 Mar 2011
Last updated
18 Jun 2018
Results posted
No
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 17515460

  • 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.

    PubMed 19913314

  • 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.

    PubMed 10889126

  • 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.

    PubMed 15145099

  • 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.

    PubMed 12633793

  • 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.

    PubMed 20510213

  • 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.

    PubMed 20510215

  • 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.

    PubMed 23067904

  • 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.

    PubMed 32855096

  • 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.

    PubMed 32522198

  • 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.

    PubMed 30219400

  • 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.

    PubMed 27888762

  • 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.

    PubMed 25129820

  • 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.

    PubMed 24694530

  • 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.

    PubMed 24002794

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Injectable (i.v.) metoprolol tartrate (up to 15 mg). in people with Myocardial Infarction, run by Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III at 12 sites in Spain.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 18 Jun 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 12 sites in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Infarct size evaluated primarily by area of delayed enhancement on cardiac magnetic resonance imaging. (time frame: 5-7 days after reperfusion). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01311700, which also lists 15 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jun 2018.

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