Cardioprotective Effect of Dexmedetomidine in Patients With ST-segment Elevation Myocardial Infarction (COOPERATION)

November 22, 2021 updated by: Yu Bo, Harbin Medical University

Cardioprotective Effect of Dexmedetomidine in Patients With ST-segment Elevation Myocardial Infarction: a Double-Blind, Multicenter, Randomized, Placebo-Controlled Clinical Trial

This is a double-blind, multicenter, randomized, placebo-controlled clinical trial. It is planned to enroll patients admitted with anterior ST-segment elevation myocardial infarction (STEMI) within 6h of symptom onset and undergo primary percutaneous coronary intervention (pPCI). Patients who meet the inclusion criteria and without exclusion criteria were randomized 1:1 into the dexmedetomidine (DEX) group or the placebo (saline) group after signing the informed consent. In the DEX group, intravenous injection of DEX was started immediately after enrollment, covering the entire PCI operation, and the administration was stopped at the end of the pPCI. The administration of saline was the same as those in the DEX group. The primary endpoint was the myocardial infarct size (MIS) as assessed by cardiac magnetic resonance imaging (CMR) at 5±2 days post-STEMI. Based on a superiority design and assuming an 20.0% relative infarct size reduction (from 26.0% to 20.8% with a SD of 13.0%), 250 patients are required to be enrolled, accounting for 20% drop-out (α= 0.05 and power= 80%).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

250

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • China
    • Anhui
      • Hefei, Anhui, China, 230000
        • Recruiting
        • The First affiliated Hospital of Anhui Medical University
        • Contact:
    • Gansu
      • Lanzhou, Gansu, China, 730000
        • Recruiting
        • The First Affiliated Hospital of Lanzhou University
        • Contact:
    • Heilongjiang
      • Harbin, Heilongjiang, China, 150000
        • Recruiting
        • The Second Affiliated Hospital of Harbin Medical University
        • Contact:
      • Mudanjiang, Heilongjiang, China, 1570011
        • Recruiting
        • Mudanjiang Cardiovascular Hospital
        • Contact:
    • Henan
      • Zhengzhou, Henan, China, 450000
        • Recruiting
        • Henan Provincial People's Hospital
        • Contact:
    • Hubei
      • Wuhan, Hubei, China, 430022
        • Recruiting
        • Wuhan Asia Heart Hospital
        • Contact:
    • Shaanxi
      • Xi'an, Shaanxi, China, 710068
        • Recruiting
        • Shaanxi Provincial People's Hospital
        • Contact:
    • Shanxi
      • Taiyuan, Shanxi, China, 30001
        • Recruiting
        • Shanxi Cardiovascular Hospital
        • Contact:
    • Tianjin
      • Tianjin, Tianjin, China, 300192
        • Recruiting
        • Tianjin First Central Hospital
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria: the enrolled subjects must meet all of the following criteria:

  • Aged 18-75 years old (inclusive);
  • Diagnosed with anterior STEMI within 6h of symptom onset: (1) ischemic chest discomfort; (2) electrocardiogram (ECG) with ST elevation ≥0.2 mV in 2 or more contiguous precordial leads (one of which should be V2, V3, or V4);
  • Sign the informed consent form.

Exclusion Criteria: subjects who meet any one of the following criteria are excluded from the study:

  • Ventricular fibrillation, cardiogenic shock, Killip III-IV grade;
  • Sinus bradycardia (heart rate sustained <60 beats/min), PR interval> 240ms or II-III degree atrioventricular block;
  • Continuous systolic blood pressure <120mmHg;
  • Severe breathing difficulties, aterial blood oxygen saturation <92%;
  • Thrombolytic therapy has been performed before the first medical contact in the hospital;
  • Consciousness disorder or past cerebrovascular disease;
  • Previous history of myocardial infarction or PCI/CABG treatment;
  • Known severe liver and kidney dysfunction;
  • Known allergy to dexmedetomidine;
  • CMR contraindications: such as claustrophobia, pacemaker or ICD implantation;
  • Pregnant or lactating women;
  • Malignant tumor or expected survival time <1 year;
  • Any condition which in the opinion of the investigator would make it unsafe or unsuitable for the patient to participate in this study (eg, poor compliance, inability of the patient to comply with study procedures and/or follow up);
  • Participate in other randomized controlled studies at the same time.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Dexmedetomidine (DEX) group
The patient began to inject DEX intravenously as soon as he enrolled. This study started with the maximum maintenance dose allowed by the label (0.7μg/kg/h). With reference to previous studies, we set 3 pump injection gradients within the range of 0.2-0.7μg/kg/h (0.2μg/kg/h, 0.45μg/kg/h, 0.7μg/kg/h), and based on the patient's heart rate , systolic blood pressure and RASS sedation score to adjust.
Drug: Dexmedetomidine (DEX)
The patient began to inject DEX intravenously as soon as he enrolled. This study started with the maximum maintenance dose allowed by the label (0.7μg/kg/h). With reference to previous studies, we set 3 pump injection gradients within the range of 0.2-0.7μg/kg/h (0.2μg/kg/h, 0.45μg/kg/h, 0.7μg/kg/h), and based on the patient's heart rate , systolic blood pressure and RASS sedation score to adjust.
Placebo Comparator: Placebo (Saline) group
The patient began intravenous injection of normal saline immediately after enrollment. The administration method and dosage adjustment of normal saline are the same as DEX group.
Drug: Placebo (Saline)
The patient began intravenous injection of normal saline immediately after enrollment. The administration method and dosage adjustment of normal saline are the same as DEX.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Myocardial infarction size (MIS) evaluated by CMR 5±2 days post-STEMI.
Time Frame: 5±2 days post-STEMI
MIS was measured by CMR delayed gadolinium enhancement（expressed as %LV myocardial mass).
5±2 days post-STEMI

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Myocardial salvage index (MSI) evaluated by CMR 5±2 days post-STEMI.
Time Frame: 5±2 days post-STEMI
MSI defined as: (area at risk - myocardial infarct size) / area at risk × 100.
5±2 days post-STEMI
Microvascular obstruction (MVO) evaluated by CMR 5±2 days post-STEMI.
Time Frame: 5±2 days post-STEMI
MVO was evaluated qualitatively on delayed enhanced images; it was defined as hypodense regions within the hyperenhanced infracted area.
5±2 days post-STEMI
Left ventricular ejection fraction (LVEF) evaluated by CMR 5±2 days post-STEMI.
Time Frame: 5±2 days post-STEMI
LVEF was defined as: (left ventricular end-diastolic volume - left ventricular end-systolic volume) / left ventricular end-diastolic volume × 100.
5±2 days post-STEMI
The area under curve (AUC) for troponin I (cTnI) and creatine kinase-MB (CK-MB).
Time Frame: First medical contact in hospital (before drug administration, baseline), and return to ward immediately, 6 Hours, 12 Hours, 24 Hours, 48 Hours after PCI procedure
Myocardial ischemic injury markers refer to CK-MB and cTnI
First medical contact in hospital (before drug administration, baseline), and return to ward immediately, 6 Hours, 12 Hours, 24 Hours, 48 Hours after PCI procedure
The peak value for troponin I (cTnI) and creatine kinase-MB (CK-MB).
Time Frame: First medical contact in hospital (before drug administration, baseline), and return to ward immediately, 6 Hours, 12 Hours, 24 Hours, 48 Hours after PCI procedure
Myocardial ischemic injury markers refer to CK-MB and cTnI
First medical contact in hospital (before drug administration, baseline), and return to ward immediately, 6 Hours, 12 Hours, 24 Hours, 48 Hours after PCI procedure
LVEF evaluated by echocardiograhy at 30 days post-STEMI.
Time Frame: 30 days post-STEMI
LVEF was defined as: (left ventricular end-diastolic volume - left ventricular end-systolic volume) / left ventricular end-diastolic volume × 100.
30 days post-STEMI
Incidence of major adverse cardiovascular events (MACE): cardiac death, recurrent myocardial infarction, revascularization, rehospitalization due to heart failure.
Time Frame: 30 days and 12 months post-STEMI
Clinical follow-up is performed at 30 days, 3 months, 6 months, and 12 months. Follow-up at 30 days is in the outpatient clinic, other time frame follow-up is performed by phone call and clinical charts review.
30 days and 12 months post-STEMI

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
The major prespecified safety endpoint: a composite of cardiac death during the first 24 hours after admission.
Time Frame: The first 24 hours after admission
A composite of cardiac death was defined death from cardiac causes
The first 24 hours after admission
The major prespecified safety endpoint: II-III degree atrioventricular block during the first 24 hours after admission.
Time Frame: The first 24 hours after admission
Atrioventricular block is defined as the abnormal conduction of electrical activation between the atria and ventricles during the conduction of electrical activation of the heart, which can lead to arrhythmia and prevent the heart from contracting and pumping blood normally.
The first 24 hours after admission
The major prespecified safety endpoint:severe sinus bradycardia during the first 24 hours after admission.
Time Frame: The first 24 hours after admission
Severe sinus bradycardia was defined as heart rate (HR) sustained <50 beats/min
The first 24 hours after admission
The major prespecified safety endpoint:severe hypotension during the first 24 hours after admission.
Time Frame: The first 24 hours after admission
severe hypotension was defined as continuous systolic blood pressure <80mmHg
The first 24 hours after admission
The major prespecified safety endpoint:malignant ventricular arrhythmia during the first 24 hours after admission.
Time Frame: The first 24 hours after admission
malignant ventricular arrhythmia including ventricular tachycardia and ventricular fibrillation.
The first 24 hours after admission

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Harbin Medical University

Collaborators

Yangtze River Pharmaceutical Group Co., Ltd.

Investigators

  • Principal Investigator: Bo Yu, M.D., FACC, The Second Affiliated Hospital of Harbin Medical University
  • Principal Investigator: Xi Su, Wuhan Asia Heart Hospital
  • Principal Investigator: Xiaohui Zheng, Henan Provincial People's Hospital
  • Principal Investigator: Jian An, Shanxi Cardiovascular Hospital
  • Principal Investigator: Xiling Shou, Shaanxi Provincial People's Hospital
  • Principal Investigator: Chengzhi Lu, Tianjin First Central Hospital
  • Principal Investigator: Xianhe Lin, The First affiliated Hospital of Anhui Medical University
  • Principal Investigator: Zheng Zhang, LanZhou University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 27, 2021

Primary Completion (Anticipated)

December 1, 2022

Study Completion (Anticipated)

December 1, 2022

Study Registration Dates

First Submitted

May 12, 2021

First Submitted That Met QC Criteria

June 2, 2021

First Posted (Actual)

June 3, 2021

Study Record Updates

Last Update Posted (Actual)

November 24, 2021

Last Update Submitted That Met QC Criteria

November 22, 2021

Last Verified

November 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • COOPERATION

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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