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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Ministerio de Sanidad, Servicios Sociales e Igualdad
Fundación Mutua Madrileña
Information provided by (Responsible Party):
Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III
ClinicalTrials.gov Identifier:
NCT01311700
First received: March 8, 2011
Last updated: February 12, 2013
Last verified: February 2013
  Purpose

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.


Condition Intervention Phase
Myocardial Infarction.
Drug: Injectable (i.v.) metoprolol tartrate (up to 15 mg).
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
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.

Resource links provided by NLM:


Further study details as provided by Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III:

Primary Outcome Measures:
  • Infarct size evaluated primarily by area of delayed enhancement on cardiac magnetic resonance imaging. [ Time Frame: 5-7 days after reperfusion ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Infarct size evaluated primarily by the area under the curve of CK, CK-MB and troponin release over the first 72 hours of reperfusion. [ Time Frame: over the first 72 hours of reperfusion. ] [ Designated as safety issue: No ]
  • Infarct size evaluated by area of delayed enhancement on cardiac magnetic resonance imaging. [ Time Frame: at month 6 ] [ Designated as safety issue: No ]
  • 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. [ Time Frame: 5-7 days after reperfusion. ] [ Designated as safety issue: No ]
  • Percent salvaged myocardium evaluated by cardiac magnetic resonance imaging. [ Time Frame: 5-7 days after reperfusion ] [ Designated as safety issue: No ]
  • Recovery of myocardial contraction assessed by magnetic resonance imaging and echocardiography. [ Time Frame: at month 6 ] [ Designated as safety issue: No ]
  • Myocardial perfusion evaluated by magnetic resonance imaging. [ Time Frame: 5-7 days post-reperfusion. ] [ Designated as safety issue: No ]
  • Composite of death, malignant ventricular arrhythmias, reinfarction or admission due to heart failure [ Time Frame: hospital discharge, 1, 6 and 12 months post-reperfusion. ] [ Designated as safety issue: No ]
  • Major cardiovascular events (death, malignant ventricular arrhythmias, AV block, cardiogenic shock, reinfarction). [ Time Frame: within first 24 hr post-reperfusion. ] [ Designated as safety issue: Yes ]

Enrollment: 221
Study Start Date: November 2010
Estimated Study Completion Date: October 2013
Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Early metoprolol initiation strategy 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.

No Intervention: Delayed metoprolol initiation strategy

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

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01311700

Locations
Spain
Hospital Marqués de Valdecilla
Santander, Cantabria, Spain, 39008
Hospital Puerta de Hierro
Majadahonda, Madrid, Spain, 28013
Hospital Universitario de Vigo-Hospital Meixoeiro
Vigo, Pontevedra, Spain, 36200
Servicio de Urgencias Sanitarias 061 de Galicia
Vigo, Pontevedra, Spain, 36204
Hospital de León
León, Spain, 24008
• Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC),
Madrid, Spain, 28029
Hospital Clínico San Carlos
Madrid, Spain, 28040
Hospital Universitario Quirón
Madrid, Spain, 28223
Servicio de Asistencia Municipal de Urgencia y Rescate (SAMUR)
Madrid, Spain, 28011
Servicio de Urgencia Médica de la Comunidad de Madrid (SUMMA) 112
Madrid, Spain, 28045
Hospital La Princesa
Madrid, Spain, 28006
Hospital 12 de Octubre
Madrid, Spain, 28041
Sponsors and Collaborators
Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III
Ministerio de Sanidad, Servicios Sociales e Igualdad
Fundación Mutua Madrileña
Investigators
Principal Investigator: Borja Ibanez, MD PhD CNIC
  More Information

Additional Information:
Publications:

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Pizarro G, Fernández-Friera L, Fuster V, Fernández-Jiménez R, García-Ruiz JM, García-Álvarez A, Mateos A, Barreiro MV, Escalera N, Rodriguez MD, de Miguel A, García-Lunar I, Parra-Fuertes JJ, Sánchez-González J, Pardillos L, Nieto B, Jiménez A, Abejón R, Bastante T, Martínez de Vega V, Cabrera JA, López-Melgar B, Guzman G, García-Prieto J, Mirelis JG, Zamorano JL, Albarrán A, Goicolea J, Escaned J, Pocock S, Iñiguez A, Fernández-Ortiz A, Sánchez-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.
Ibanez B, Macaya C, Sánchez-Brunete V, Pizarro G, Fernández-Friera L, Mateos A, Fernández-Ortiz A, García-Ruiz JM, García-Álvarez A, Iñiguez A, Jiménez-Borreguero J, López-Romero P, Fernández-Jiménez R, Goicolea J, Ruiz-Mateos B, Bastante T, Arias M, Iglesias-Vázquez JA, Rodriguez MD, Escalera N, Acebal C, Cabrera JA, Valenciano J, Pérez de Prado A, Fernández-Campos MJ, Casado I, García-Rubira JC, García-Prieto J, Sanz-Rosa D, Cuellas C, Hernández-Antolín R, Albarrán A, Fernández-Vázquez F, de la Torre-Hernández 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.

Responsible Party: Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III
ClinicalTrials.gov Identifier: NCT01311700     History of Changes
Other Study ID Numbers: METOCARD-CNIC, CNIC translational Grant 2009, 2010-019939-35, Ministerio de Sanidad
Study First Received: March 8, 2011
Last Updated: February 12, 2013
Health Authority: Spain: Spanish Agency of Medicines

Keywords provided by Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III:
Ischemia
Reperfusion
Myocardial infarction
Beta blockers
Metoprolol
Acute myocardial infarction
Necrosis
Salvaged Myocardium

Additional relevant MeSH terms:
Infarction
Myocardial Infarction
Cardiovascular Diseases
Heart Diseases
Ischemia
Myocardial Ischemia
Necrosis
Pathologic Processes
Vascular Diseases
Metoprolol
Metoprolol succinate
Adrenergic Agents
Adrenergic Antagonists
Adrenergic beta-1 Receptor Antagonists
Adrenergic beta-Antagonists
Anti-Arrhythmia Agents
Antihypertensive Agents
Autonomic Agents
Cardiovascular Agents
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Sympatholytics
Therapeutic Uses

ClinicalTrials.gov processed this record on October 22, 2014