Cardioprotection, Percutaneous Coronary Intervention, ST-segment Elevation Myocardial Infarction (STEMI)
Conditions
Keywords
ST-segment Elevation Myocardial Infarction (STEMI), Percutaneous coronary intervention, Dexmedetomidine, Cardioprotection
Brief summary
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%).
Interventions
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.
DRUGPlacebo (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.
Sponsors
Yangtze River Pharmaceutical Group Co., Ltd.
Harbin Medical University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Myocardial infarction size (MIS) evaluated by CMR 5±2 days post-STEMI. | 5±2 days post-STEMI | MIS was measured by CMR delayed gadolinium enhancement（expressed as %LV myocardial mass). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Microvascular obstruction (MVO) evaluated by CMR 5±2 days post-STEMI. | 5±2 days post-STEMI | MVO was evaluated qualitatively on delayed enhanced images; it was defined as hypodense regions within the hyperenhanced infracted area. |
| Left ventricular ejection fraction (LVEF) evaluated by CMR 5±2 days post-STEMI. | 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. |
| The area under curve (AUC) for troponin I (cTnI) and creatine kinase-MB (CK-MB). | 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 |
| The peak value for troponin I (cTnI) and creatine kinase-MB (CK-MB). | 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 |
| LVEF evaluated by echocardiograhy at 30 days post-STEMI. | 30 days post-STEMI | LVEF was defined as: (left ventricular end-diastolic volume - left ventricular end-systolic volume) / left ventricular end-diastolic volume × 100. |
| Incidence of major adverse cardiovascular events (MACE): cardiac death, recurrent myocardial infarction, revascularization, rehospitalization due to heart failure. | 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. |
| Myocardial salvage index (MSI) evaluated by CMR 5±2 days post-STEMI. | 5±2 days post-STEMI | MSI defined as: (area at risk - myocardial infarct size) / area at risk × 100. |
Other
| Measure | Time frame | Description |
|---|---|---|
| The major prespecified safety endpoint:severe sinus bradycardia during the first 24 hours after admission. | The first 24 hours after admission | Severe sinus bradycardia was defined as heart rate (HR) sustained \<50 beats/min |
| The major prespecified safety endpoint:severe hypotension during the first 24 hours after admission. | The first 24 hours after admission | severe hypotension was defined as continuous systolic blood pressure \<80mmHg |
| The major prespecified safety endpoint:malignant ventricular arrhythmia during the first 24 hours after admission. | The first 24 hours after admission | malignant ventricular arrhythmia including ventricular tachycardia and ventricular fibrillation. |
| The major prespecified safety endpoint: II-III degree atrioventricular block during the first 24 hours after admission. | 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 major prespecified safety endpoint: a composite of cardiac death during the first 24 hours after admission. | The first 24 hours after admission | A composite of cardiac death was defined death from cardiac causes |
Countries
China
Contacts
Primary ContactJiannan Dai, M.D., Ph.D
Backup ContactJinfeng Tan, M.D.
Outcome results
None listed