Biomarker-guided Implementation of Angiotensin-II (AT-II) to Reduce the Occurrence of Kidney Damage After Cardiac Surgery
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 64
- 试验地点
- 1
- 主要终点
- • kidney damage after cardiac surgery identified by the difference between [TIMP-2]*[IGFBP7] levels 12h after randomization and [TIMP-2]*[IGFBP7] levels at randomization
研究概览
简要总结
The aim of this study is to evaluate whether adding angiotensin II to the standard of care is superior compared to the standard of care alone with respect to kidney damage (personalized approach) after cardiac surgery.
详细描述
Vasoplegic syndrome is a form of distributive shock that is characterized by low arterial pressure with reduced systemic vascular resistance and normal or elevated cardiac output that occurs in 5 to 25% of patients undergoing cardiac surgery. Patients with vasoplegic shock after cardiac surgery are at higher risk of organ failure, including acute kidney injury (AKI). Postsurgical AKI is associated with several adverse outcomes. Attempts to prevent AKI have largely been futile so far. Prior studies often started with the interventions after an AKI event, when a decline of kidney function (i.e. glomerular filtration rate) was already established. Application of norepinephrine is currently considered as the first-line therapy for vasoplegic shock, but all catecholamines have adverse effects, including myocardial ischemia and arrhythmias. In a recent observational trial, we demonstrated that there is a dysregulation in the renin-angiotensin-aldosterone system (RAAS) likely caused by a reduced angiotensin-converting enzyme (ACE) activity after cardiac surgery. Elevated renin levels identified patients at risk for AKI and were associated with cardiovascular instability and increased AKI rate after cardiac surgery. Furthermore, elevated renin levels could be used to identify high-risk patients for cardiovascular instability and AKI who would benefit from timely intervention with angiotensin II that could improve their outcomes. Therefore, the application of angiotensin II to treat a postoperative hypotension would mean a hormone substitution.Shock after cardiac surgery is associated with increased mortality. Cardiopulmonary bypass (CPB) represents a common clinical setting of sympathetic nervous system activation and cardiovascular instability. Vasoplegia is a form of distributive shock that is characterized by low arterial pressure with reduced systemic vascular resistance and normal or elevated cardiac output. It occurs in 5 to 25% of patients undergoing cardiac surgery. Patients with vasoplegia after cardiac surgery are at higher risk of organ failure, including AKI, and have an increased mortality rate and longer hospital length of stay.
Clinical trials focusing on septic patients suggest that AT-II is a potent vasopressor. However, no human data exist whether the application of AT-II in cardiac surgery patients with y hyperreninemia high-risk patients identified by renin levels (individualized approach) reduces kidney damage and improves kidney function after cardiac surgery.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult patients undergoing cardiac surgery with CPB
- •Cardiac index 2.1l/min per square meter
- •Written informed consent
- •D-renin (difference between post- and preoperative) ≥ 3.7 micro Unit/ml 4 h after CPB
- •Postoperative hypotension requiring vasopressors
排除标准
- •Preexisting AKI (stage 1 and higher)
- •Patients with cardiac assist devices
- •Pregnant women, nursing women and women of childbearing potential
- •Known (Glomerulo-) Nephritis, interstitial nephritis or vasculitis
- •chronic kidney disease with estimated glomerular filtration rate (eGFR) < 30 ml/min
- •Dialysis dependent chronic kidney disease
- •Prior kidney transplant within the last to 12 months
- •Emergency surgery in the context of an acute coronary syndrome
- •Hypersensitivity to the active substance, or to any of the excipients of the study medication
- •Bronchospasm
- •Liver failure
- •Mesenteric ischemia
- •Participation in another intervention trial in the past 3 months
- •Persons with any kind of dependency on the investigator or employed by the institution responsible or investigator
- •Persons held in an institution by legal or official order
研究组 & 干预措施
Angiotensin II
Intravenous infusion of max. 80 ng/kg/min Angiotensin II (titrated for each individual patient by effect) over 12 h after start of infusion
干预措施: Angiotensin II (Drug)
Control
Intravenous infusion placebo (matched infusion volume) over 12 h after start of infusion
干预措施: Control (Drug)
结局指标
主要结局
• kidney damage after cardiac surgery identified by the difference between [TIMP-2]*[IGFBP7] levels 12h after randomization and [TIMP-2]*[IGFBP7] levels at randomization
时间窗: 12 hours after start of intervention
The presence of tissue inhibitor of metalloproteinases (TIMP-2) and insulin-like growth-factor binding protein 7 (IGFBP7) in the urine will be measured.
次要结局
- Occurence of Acute Kidney Injury (AKI) according to the Kidney Disease: Improving Global Outcomes (KDIGO) criteria(72 hours after cardiac surgery)
- Severity of Acute Kidney Injury(72 hours after cardiac surgery)
- Amount of volume application(12 hours after start of intervention)
- Fluid status(12 hours after start of intervention)
- Dose of vasopressor use during intervention(During intervention, an average of 12 hours)
- Creatinine clearance on day one after cardiac surgery(One day after cardiac surgery)
- Free-days through day 28 of vasoactive medications and mechanical ventilation(28 days after cardiac surgery)
- Renal Recovery(90 days after cardiac surgery)
- Mortality(90 days after cardiac surgery)
- Length of ICU (Intensive Care Unit) stay(up to 90 days after cardiac surgery (until discharge))
- Length of hospital stay(up to 90 days after cardiac surgery (until discharge))
- Use and duration of renal replacement therapy(up to 90 days after cardiac surgery)
- Major adverse kidney events (MAKE)(90 days after cardiac surgery)
- Effect of Angiotensin converting enzyme inhibitor (ACEi)/angiotensin II receptor blocker (ARBs) use on the effect of angiotensin II(12 hours after intervention)
- Correlation between the severity of hyperreninemia and the effect of angiotensin II(12 hours after intervention)