Effect of Intravenous Metoprolol Combining RIC on Myocardial Protection in STEMI Patients

Combined Metoprolol and Remote Ischemic Conditioning in Cardioprotection of Anterior ST-segment Elevation Myocardial Infarction (METRICATION)

The main purpose of this study is to compare the myocardial protection effect of intravenous metoprolol combined with remote ischemic conditioning (RIC) and single treatment before reperfusion in Chinese patients with anterior STEMI. This study sought to find possible strategies to further improve myocardial protection in Chinese patients with anterior STEMI.

Study Overview

• Status: Completed
• Conditions: Heart Failure; Anterior Myocardial Infarction
• Intervention / Treatment: Drug: intravenous Placebo; Drug: Metoprolol Injectable Product; Device: Romote Ischemic Conditioning (RIC); Combination product: Metoprolol & RIC

Detailed Description

This study is a prospective, multi-center, randomized controlled study. It is planned to enroll 1200 patients with anterior STEMI. Immediately after the first medical contact, the patients who were determined by the investigator to meet the inclusion/exclusion criteria were randomized through the interactive web response system (IWRS) and received different pre-reperfusion treatments. The four groups were placebo group, metoprolol group, remote ischemic conditioning (RIC) group and metoprolol & RIC group. Subsequently, the investigator conduct diagnosis and treatment according to the patient's specific conditions and check the serum level of myocardial damage markers (i.e. CK and CK-MB) at the time of admission, 12, 24, 36, 48, 60 hours, respectively. If the patient undergoes PCI treatment, additional detection of myocardial damage markers immediately after PCI is also required. All patients were followed for 1 year with an office visit or a telephone call at 1, 3, 6, 9 and 12 months to evaluate the health status and adverse clinical events of patients.

• Study Type: Interventional
• Enrollment (Actual): 1206
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100044
      • Peking Univerisity People'Hospital
    • Beijing, Beijing, China
      • Beijing CHAO-YANG Hospital, Capital Medical University
  • Guangdong
    • Guangzhou, Guangdong, China
      • Guangdong General Hospital
  • Hebei
    • Shijiazhuang, Hebei, China
      • Second Hospital of Hebei Medical University
  • Heilongjiang
    • Daqing, Heilongjiang, China, 163001
      • Daqing Oilfield General Hospital
  • Henan
    • Zhengzhou, Henan, China
      • The first affiliated hospital of Zhengzhou medical university
  • Jiangsu
    • Nanjing, Jiangsu, China, 210009
      • Zhongda Hospital Southeast University
  • Jiangxi
    • Nanchang, Jiangxi, China, 330006
      • The Second Affiliated Hospital of Nanchang University
  • Jilin
    • Changchun, Jilin, China, 130000
      • The Second Hospital of Jilin University
  • Liaoning
    • Dalian, Liaoning, China
      • The Second Affiliated Hospital of Dalian Medical University
    • Shenyang, Liaoning, China
      • Shenyang military district general hospital of the people's liberation army
  • Shanxi
    • Xi'an, Shanxi, China
      • The first affiliated hospital of military medical university
  • Sichuan
    • Chongqing, Sichuan, China
      • Third Military Medical University
  • Tianjin
    • Tianjin, Tianjin, China
      • The General Hospital of Tianjin Medical University
    • Tianjing, Tianjin, China
      • Tianjin Chest Hospital
  • Xinjiang
    • Urumqi, Xinjiang, China
      • The First Affiliated Hospital of Xinjiang Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. ages 18 to 80 years;
2. presenting within 12 h of symptoms onset, with anterior STEMI and planned for pPCI; anterior STEMI was defined as the occurrence of >20 min of chest pain and ST-segment elevation (>2 mm) in at least 2 contiguous precordial leads;
3. sign informed consent;

Exclusion Criteria:

1. systolic blood pressure < 110mmHg;
2. cardiogenic shock or with heart failure symptoms, Killip III~IV;
3. allergic history of metoprolol;
4. history of asthma or the need for bronchodilators;
5. PR interval > 240ms, II~III atrioventricular block；
6. heart rate < 60 beats/min;
7. unable to consent;
8. pregnancy and lactation women;
9. life expectancy for diseases (i.e. cancer) < 1 year.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo group; Patients receive intravenous placebo injection.	Drug: intravenous Placebo; Patients receive intravenous Placebo (saline) injection
Experimental: Intravenous metoprolol group; Patients receive intravenous metoprolol injection.	Drug: Metoprolol Injectable Product; Patients receive intravenous Metoprolol injection
Experimental: RIC group; Patients receive RIC treatment.	Device: Romote Ischemic Conditioning (RIC); Patients receive RIC treatment
Experimental: Intravenous metoprolol and RIC group; Patients receive intravenous metoprolol injection and RIC treatment.	Combination product: Metoprolol & RIC; Patients receive Metoprolol & RIC treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Myocardial infarct size	Estimating myocardial infarct size by area under CK, CK-MB curve	60 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major adverse cardiac and cerebrovascular events (MACCE)	Composition of death, heart failure, reinfarction, revascularization, malignant ventricular arrhythmias, stroke)	1 year
Incidence of heart failure	Incidence of heart failure	1 year
myocardial infarct size measured by MRI (optional)	myocardial infarct size measured by MRI (optional)	7 days after AMI
Safety endpoint: incidence of severe bradycardia or hypotension	Severe bradycardia (heart rate <40bpm) or hypotension (systolic blood pressure <80mmHg)	24 hours

Collaborators and Investigators

• Sponsor: Harbin Medical University
• Collaborators: Beijing Chao Yang Hospital

Study record dates

Study Major Dates

• Study Start (Actual): November 28, 2017
• Primary Completion (Actual): August 31, 2020
• Study Completion (Actual): August 30, 2021

Study Registration Dates

• First Submitted: May 17, 2018
• First Submitted That Met QC Criteria: July 5, 2018
• First Posted (Actual): July 9, 2018

Study Record Updates

• Last Update Posted (Actual): November 4, 2021
• Last Update Submitted That Met QC Criteria: October 27, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: Myocardial Protection; RIC; Anterior Myocardial Infarction; Intravenous Metoprolol
• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Myocardial Infarction; Infarction; Anterior Wall Myocardial Infarction; Physiological Effects of Drugs; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Autonomic Agents; Peripheral Nervous System Agents; Sympatholytics; Adrenergic beta-1 Receptor Antagonists; Metoprolol
• Other Study ID Numbers: 2016YFC1301102

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No