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

Официальное название

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

Обзор

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%).

Вмешательства

• Препарат 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.
• Препарат 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.

Первичные конечные точки

• Myocardial infarction size (MIS) evaluated by CMR 5±2 days post-STEMI. [Срок оценки: 5±2 days post-STEMI]

Вторичные конечные точки (7)

• Myocardial salvage index (MSI) evaluated by CMR 5±2 days post-STEMI. [Срок оценки: 5±2 days post-STEMI]
• Microvascular obstruction (MVO) evaluated by CMR 5±2 days post-STEMI. [Срок оценки: 5±2 days post-STEMI]
• Left ventricular ejection fraction (LVEF) evaluated by CMR 5±2 days post-STEMI. [Срок оценки: 5±2 days post-STEMI]
• The area under curve (AUC) for troponin I (cTnI) and creatine kinase-MB (CK-MB). [Срок оценки: 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). [Срок оценки: 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. [Срок оценки: 30 days post-STEMI]
• Incidence of major adverse cardiovascular events (MACE): cardiac death, recurrent myocardial infarction, revascularization, rehospitalization due to heart failure. [Срок оценки: 30 days and 12 months post-STEMI]

Критерии участия

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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Двойное слепое

Основная цель

Профилактика

Центры проведения

Китай · 9 центров

• The First Affiliated Hospital of Anhui Medical University — Хэфэй
• The First Affiliated Hospital of Lanzhou University — Lanzhou
• The Second Affiliated Hospital of Harbin Medical University — Харбин
• Mudanjiang Cardiovascular Hospital — Mudanjiang
• Henan Provincial People's Hospital — Чжэнчжоу
• Wuhan Asia Heart Hospital — Ухань
• Shaanxi Provincial People's Hospital — Сиань
• Shanxi Cardiovascular Hospital — Taiyuan
• … и ещё 1 центр

Публикации

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• 2. The World Bank. Toward a healthy and harmonious life in China: stemming the rising tide of non-communicable diseases. http://www.worldbank.org/content/dam/Worldbank/document/NCD_ report_en.pdf (accessed Nov 27, 2013).
• Li J, Li X, Wang Q, Hu S, Wang Y, Masoudi FA, Spertus JA, Krumholz HM, Jiang L; China PEACE Collaborative Group. ST-segment elevation myocardial infarction in China from 2001 to 2011 (the China PEACE-Retrospective Acute Myocardial Infarction Study): a retrospective analysis of hospital data. Lancet. 2015 Jan 31;385(9966):441-51. doi: 10.1016/S0140-6736(14)60921-1. Epub 2014 Jun 23. PMID 24969506
• Stone GW, Selker HP, Thiele H, Patel MR, Udelson JE, Ohman EM, Maehara A, Eitel I, Granger CB, Jenkins PL, Nichols M, Ben-Yehuda O. Relationship Between Infarct Size and Outcomes Following Primary PCI: Patient-Level Analysis From 10 Randomized Trials. J Am Coll Cardiol. 2016 Apr 12;67(14):1674-83. doi: 10.1016/j.jacc.2016.01.069. PMID 27056772
• Frohlich GM, Meier P, White SK, Yellon DM, Hausenloy DJ. Myocardial reperfusion injury: looking beyond primary PCI. Eur Heart J. 2013 Jun;34(23):1714-22. doi: 10.1093/eurheartj/eht090. Epub 2013 Mar 27. PMID 23536610
• Heusch G. Myocardial ischaemia-reperfusion injury and cardioprotection in perspective. Nat Rev Cardiol. 2020 Dec;17(12):773-789. doi: 10.1038/s41569-020-0403-y. Epub 2020 Jul 3. PMID 32620851
• Hausenloy DJ, Botker HE, Engstrom T, Erlinge D, Heusch G, Ibanez B, Kloner RA, Ovize M, Yellon DM, Garcia-Dorado D. Targeting reperfusion injury in patients with ST-segment elevation myocardial infarction: trials and tribulations. Eur Heart J. 2017 Apr 1;38(13):935-941. doi: 10.1093/eurheartj/ehw145. No abstract available. PMID 27118196
• 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, PMID 24002794

Идентификаторы

NCT: NCT04912518 · COOPERATION

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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