LOW-DOSE DOBUTAMINE INFUSION AND SINGLE-DOSE TOCILIZUMAB IN ACUTE MYOCARDIAL INFARCTION PATIENTS WITH HIGH RISK OF CARDIOGENIC SHOCK DEVELOPMENT (DOBERMANN) - A 2X2 MULTIFACTORIAL, DOUBLE-BLINDED, RANDOMIZED, PLACEBO-CONTROLLED TRIAL
试验速览
- 阶段
- 4 期
- 状态
- 进行中（未招募）
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- NTproBNP in blood samples drawn from hospital admission to 48 hours after admission.
研究概览
简要总结
In the present study, we aim to investigate the effects of dobutamine infusion and/or a single post-PCI intravenous (IV) dose of Tocilizumab on plasma concentration of NTproBNP as a proxy for development of hemodynamic instability / CS in patients with acute myocardial infarction (AMI) presenting < 24 hours from chest pain plus intermediate to high risk of CS assessed by the ORBI risk score (≥11 – not in overt shock at hospital admission).
详细描述
The planned study is an investigator-initiated, randomized, double blinded clinical trial.
Consecutive patients at Copenhagen University Hospital, Rigshospitalet admitted with AMI < 24 hours from chest pain will be screened.
Patients eligible for trial inclusion will be randomized 2:2 to receive a continuous IV dobutamine infusion of 5 mcg/kg/minute versus placebo for 24 hours and to receive a single IV dose of tocilizumab (1-hour infusion) versus placebo administered after PCI.
Treatment with the investigational drug will be initiated as soon as possible but no later than 2 hours after transfer to the coronary care unit (CCU) and after informed consent. All included patients will follow usual treatment according to current guidelines.
The biomarker proBNP will be measured in blood samples drawn upon hospital admission in patients with ORBI risk score ≥10, and after 12, 24, 36 and 48 hours from admission.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Factorial
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 years 至 65+ years（65+ Years, 18-64 Years）
- 接受健康志愿者
- 是
入选标准
- •Acute myocardial infarction
- •Revascularization with PCI
- •Presentation within 24 hours of chest pain
- •ORBI risk score ≥ 10
- •Age ≥ 18 years
排除标准
- •Comatose after cardiac arrest
- •Immune deficiency/treatment with immunosuppressants
- •Known, uncontrolled gastrointestinal (GI) disease predisposing to GI perforation
- •Unwilling to give informed consent to study participation
- •Unable to give consent due to language barrier
- •Cardiogenic shock with systolic blood pressure <100 mmHg for more than 30 minutes or need for vasopressor to maintain blood pressure and arterial lactate >2.5 (2.0) mmol/L developed before leaving the cath. lab.
- •Other major clinical non-coronary condition (stroke, sepsis etc.), which can explain a high ORBI risk score
- •Referral for acute coronary artery bypass grafting (CABG) (<24 hours) after the CAG, whereas subacute (>24 hours will be included)
- •Contraindications against dobutamine infusion (sustained ventricular tachycardia prior to admission or noted in the cath.lab., known pheochromocytoma, idiopathic hypertrophic subaortic stenosis)
- •Tocilizumab allergy
- •Pregnant- or breastfeeding women
- •Known liver disease/dysfunction
- •Ongoing uncontrollable infection
结局指标
主要结局
NTproBNP in blood samples drawn from hospital admission to 48 hours after admission.
NTproBNP in blood samples drawn from hospital admission to 48 hours after admission.
次要结局
- Infarct size measured by cMRi during index admission and after 3 months
- Biomarkers reflecting neurohormonal activation, endothelial function/damage, inflammation (pro- and anti-inflammatory processes – including IL-6 and C-reactive peptide (CRP)), connec-tive tissue damage, organ dysfunction, and other relevant processes
- 2D echocardiographic measurements of hemodynamics (VTI) and left ventricular function including strain measurements according to protocol
- SOFA score (PaO2, FiO2, on medical ventilation, Platelets, GCS, Bilirubin, mean arterial pressure OR administration of vasoactive agents required, Creatinine, COVID-19 status)
- Development of in-hospital CS and/or in-hospital cardiac arrest and/or transfer to the ICU during index admission
- Long-term all-cause mortality
- PCI operator's post-procedure clinical assessment of the patient (survives to discharge 'yes/no')
- Development of non-cardiac arrest arrythmia (sustained ventricular tachycardia, atrial fibrillation with a frequency above 120 for more than 30 minutes) during index admission (safety)
- Re-admission (all cause and cardiovascular) during the first year after index hospitalization
- Re-admission with heart failure and re-infarction during the first year after index hospitalization
- Quality of Life and mental and cognitive health at baseline and after three months
研究者
Helle Søholm
Scientific
Rigshospitalet