Biomarker-guided Implementation of Glutamine to Reduce the Occurence of AKI After Cardiac Surgery
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 64
- 试验地点
- 1
- 主要终点
- Kidney damage after cardiac surgery identified by measuring biomarkers ([TIMP-2]*[IGFBP7]
研究概览
简要总结
The aim of this study is to evaluate whether the application of glutamine versus control in patients with high risk for AKI identified by biomarkers can reduce kidney damage after cardiac surgery.
详细描述
Cardiac surgery is characterized by an increased production of free radicals as a consequence of surgical trauma, ischemia-reperfusion injury, inflammatory response syndrome in response to the use of the extracorporeal circulation. This results in an increased production and release of free radicals which may lead to an exhaustion of antioxidants and organ failure since the lungs, kidneys, liver and gastrointestinal tract are particularly susceptible to reactive oxidant species. Glutamine is considered as a conditionally indispensable amino acid in catabolic states of critically ill patients. It belongs, together with other mediators, to the host defense as major intracellular direct free radical scavengers. Its depletion has been demonstrated to be an independent predictor of mortality in a group of ICU (intensive care unit) patients. Clinical studies showed a positive outcome effect. In animal models, glutamine reduces the occurrence of AKI after ischemia-reperfusion injury. This could be demonstrated through reduced functional markers as well as reduced renal biomarker levels. Preliminary data suggest that glutamine has pleiotropic effects since it has effects on the immune system (reduced expression of cytokines) as well as on tubular epithelial cells (unpublished animal data from our laboratory).
Thus, a randomized-controlled trial to analyze the effects of glutamine supplementation in high risk patients identified by renal biomarkers undergoing cardiac surgery with cardiopulmonary bypass (CPB) on the effects of kidney damage is urgently needed.
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 90 Years（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
- •Urinary [TIMP-2]*[IGFBP7] >= 0.3 4h after CPB
- •Written informed consent
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 (CKD) with estimated glomerular filtration rate (eGFR) < 30 ml/min
- •Dialysis dependent CKD
- •Prior kidney transplant within the last to 12 months
- •Hypersensitivity to the active substance, or to any of the excipients of the study medication
- •Hepatic insufficiency
- •Severe metabolic acidosis (pH < 7.2)
- •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
Glutamine group
Intravenous infusion of 0.5 g/kg body weight (2.5 ml/kg body weight) L-alanyl-Lglutamine over 12 h after randomization
干预措施: L-Alanyl/L-Glutamine (Drug)
Control group
Intravenous infusion of 2.5 ml/kg body weight sodium chloride 0.9 % over 12 h after randomization
干预措施: Placebo (Drug)
结局指标
主要结局
Kidney damage after cardiac surgery identified by measuring biomarkers ([TIMP-2]*[IGFBP7]
时间窗: 12 hours after cardiac surgery
The presence of tissue inhibitor of metalloproteinases (TIMP-2) and insulin-like grwoth-factor binding protein 7 (IGFBP7) in the urine will be measured.
次要结局
- Occurence of acute kidney injury according to the KDIGO (Kidney Disease: Improving Global Outcomes) criteria(72 hours after end of cardiac surgery)
- Severity of acute kidney injury (number of patients with KDIGO stage 1, KDIGO stage 2 or KDIGO stage 3)(72 hours after end of cardiac surgery)
- Creatinine Clearance(one day after cardiac surgery)
- Free-days of vasoactive medications and mechanical ventilation(28 days after cardiac surgery)
- Renal recovery(90 days after cardiac surgery)
- Mortality(90 days after cardiac surgery)
- ICU and Hospital stay(up to 90 days after cardiac surgery (until discharge))
- Number of patients with renal replacement therapy(up to 90 days after cardiac surgery)