NCT01311700

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
221

participants targeted

Target at P75+ for phase_4

Timeline
Completed

Started Nov 2010

Longer than P75 for phase_4

Geographic Reach
1 country

12 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

November 1, 2010

Completed
4 months until next milestone

First Submitted

Initial submission to the registry

March 8, 2011

Completed
1 day until next milestone

First Posted

Study publicly available on registry

March 9, 2011

Completed
1.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 1, 2012

Completed
5 years until next milestone

Study Completion

Last participant's last visit for all outcomes

October 1, 2017

Completed
Last Updated

June 18, 2018

Status Verified

December 1, 2017

Enrollment Period

1.9 years

First QC Date

March 8, 2011

Last Update Submit

June 15, 2018

Conditions

Myocardial Infarction

Keywords

IschemiaReperfusionMyocardial infarctionBeta blockersMetoprololAcute myocardial infarctionNecrosisSalvaged Myocardium

Outcome Measures

Primary Outcomes (1)

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

    5-7 days after reperfusion

Secondary Outcomes (8)

  • 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.

    at month 6

  • 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

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

    at month 6

  • +3 more secondary outcomes

Study Arms (2)

Early metoprolol initiation strategy

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

Delayed metoprolol initiation strategy

NO INTERVENTION

Interventions

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.

Early metoprolol initiation strategy

Eligibility Criteria

Age18 Years - 80 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (12)

Hospital Marqués de Valdecilla

Santander, Cantabria, 39008, Spain

Location

Hospital Puerta de Hierro

Majadahonda, Madrid, 28013, Spain

Location

Hospital Universitario de Vigo-Hospital Meixoeiro

Vigo, Pontevedra, 36200, Spain

Location

Servicio de Urgencias Sanitarias 061 de Galicia

Vigo, Pontevedra, 36204, Spain

Location

Hospital de León

León, 24008, Spain

Location

Hospital La Princesa

Madrid, 28006, Spain

Location

Servicio de Asistencia Municipal de Urgencia y Rescate (SAMUR)

Madrid, 28011, Spain

Location

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

Madrid, 28029, Spain

Location

Hospital Clínico San Carlos

Madrid, 28040, Spain

Location

Hospital 12 de Octubre

Madrid, 28041, Spain

Location

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

Madrid, 28045, Spain

Location

Hospital Universitario Quirón

Madrid, 28223, Spain

Location

Related Publications (15)

  • 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.

    PMID: 17515460BACKGROUND

  • 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.

    PMID: 19913314BACKGROUND

  • 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.

    PMID: 10889126BACKGROUND

  • 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.

    PMID: 15145099BACKGROUND

  • 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.

    PMID: 12633793BACKGROUND

  • 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.

    PMID: 20510213BACKGROUND

  • 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.

    PMID: 20510215BACKGROUND

  • 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.

    PMID: 23067904BACKGROUND

  • 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.

    PMID: 32855096DERIVED

  • 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.

    PMID: 32522198DERIVED

  • 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.

    PMID: 30219400DERIVED

  • 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.

    PMID: 27888762DERIVED

  • 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.

    PMID: 25129820DERIVED

  • 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.

    PMID: 24694530DERIVED

  • 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.

    PMID: 24002794DERIVED

Related Links

MeSH Terms

Conditions

Myocardial InfarctionIschemiaNecrosis

Interventions

InjectionsMetoprolol

Condition Hierarchy (Ancestors)

Myocardial IschemiaHeart DiseasesCardiovascular DiseasesVascular DiseasesInfarctionPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Drug Administration RoutesDrug TherapyTherapeuticsPhenoxypropanolaminesPropanolaminesAmino AlcoholsAlcoholsOrganic ChemicalsPropanolsAmines

Study Officials

  • Borja Ibanez, MD PhD

    CNIC

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 8, 2011

First Posted

March 9, 2011

Study Start

November 1, 2010

Primary Completion

October 1, 2012

Study Completion

October 1, 2017

Last Updated

June 18, 2018

Record last verified: 2017-12

Locations

ES(12)