Perioperative Nitric oxiDE-conditioning, Produced by Plasma-chemical Synthesis Technology, For prevEnt Acute kidNey Injury During carDiac surgEry in Patients With chRonic Kidney Disease (DEFENDER-trial)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 136
- 试验地点
- 1
- 主要终点
- Incidence of AKI (%)
研究概览
简要总结
The protective nitric oxide (NO) effects are mediated by selective pulmonary vasodilation and improvement of arterial oxygenation in hypoxemic patients by reducing intrapulmonary shunting and improving ventilation-perfusion coordination. Inhaled NO has been used for years to treat acute respiratory failure and pulmonary hypertension in anesthesia and intensive care. The nephroprotective role of NO was studied in an experimental model of contrast-induced nephropathy. The primary aim of this prospective, double-blind, randomized, parallel-group, controlled trial is to test the hypothesis that perioperative conditioning of patients with NO at a dose of 80 ppm, obtained by plasma-chemical synthesis technology, through a ventilator and an extracorporeal circulation circuit reduces the incidence of acute kidney injury (AKI) in patients with an initially high risk of kidney damage due to the presence of preoperative chronic kidney disease (CKD). The study is interventional. Examination and treatment of patients is carried out in accordance with the approved standards of medical care for the relevant diseases. During the study, no experimental or unregistered (not approved for use) medical or diagnostic procedures in the territory of the Russian Federation will be carried out. The study includes patients admitted to the Cardiac Surgery Department of Cardiology Research Institute of Tomsk NRMC for elective surgery with high risk of AKI in the perioperative period
详细描述
NO abruptly relaxes vascular smooth muscle, leading to pulmonary vasodilation without appreciable hemodynamic effect on extrapulmonary vessels (selective pulmonary vasodilation). In addition, NO expands the smooth muscle of constricted bronchi, which may improve arterial oxygenation in hypoxemic patients by reducing intrapulmonary shunting and improving ventilation-perfusion coordination. NO has been used for many years to treat acute respiratory failure and pulmonary hypertension in anesthesia and intensive care. Several experimental and clinical studies have demonstrated extrapulmonary effects of NO, predominantly on diuresis and natriuresis, platelet function, and modulation of the immune response. The nephroprotective role of NO was studied in an experimental model of contrast-induced nephropathy.
This study is prospective, double-blind, randomized, parallel-group, controlled trial. In regard to medical procedures, this study is interventional. Examination and treatment of patients is carried out in accordance with the approved standards of medical care for the relevant diseases. During this study, no experimental or unregistered (not approved for use) medical or diagnostic procedures in the territory of the Russian Federation is carried out.
The primary aim of the study is to test the hypothesis that perioperative conditioning of patients with NO at a dose of 80 ppm, obtained by plasma-chemical synthesis technology, through a ventilator and an extracorporeal circulation circuit reduces the incidence of AKI in patients with an initially high risk of kidney damage due to the presence of preoperative CKD.
Secondary objectives of the study include the following:
- To test the hypothesis that perioperative conditioning of patients with NO at a dose of 80 ppm, obtained using plasma-chemical synthesis technology, through the ventilator circuit and the extracorporeal circulation circuit is associated with an improvement in regional kidney oximetry.
- To test the hypothesis that the method of monitoring regional kidney oximetry in the para-infrared spectrum is an effective intraoperative method for quantifying the organoprotective effect of NO-therapy.
- To test the hypothesis that perioperative conditioning of patients with NO at a dose of 80 ppm, obtained by plasma-chemical synthesis technology, through the ventilator circuit and the extracorporeal circulation circuit is associated with optimization of endogenous NO homeostasis, determined by the level of NO in the air exhaled by the patient.
- To test the hypothesis that perioperative conditioning of patients with NO at a dose of 80 ppm, obtained using plasma-chemical synthesis technology, through the ventilator circuit and the extracorporeal circulation circuit is associated with an improvement in the global oxygen status of the body, assessed using ΔPCO2/ΔContO2.
- To test the hypotheses that perioperative conditioning of patients with NO at a dose of 80 ppm, obtained using the plasma-chemical synthesis technology through the ventilator circuit and the extracorporeal circulation circuit, reduces the frequency and severity of other organ damage and complications: cardiac, pulmonary, hemorrhagic, neurological, infectious complications, multiple organ failure after surgery, duration of mechanical ventilation, time of stay in the intensive care unit, in-hospital and 30-day mortality in patients with CKD.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Triple (Participant, Care Provider, 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
- •Cardiac surgery with CPB
- •Age > 18 years
- •Signed informed consent
- •CKD (cGFR <60 mL/min/1.73 m2)
- •Positive decision of council of physicians on individual safety of perioperative administration of NO
排除标准
- •Emergency surgery (including that in ACS)
- •cGFR <15 mL/min/1.73 m2
- •Administration of potentially nephrotoxic drugs within 24 hours before surgery (radiocontrast agents, antimicrobial therapy with aminoglycosides and / or amphotericin)
- •Critical preoperative status (preoperative need for mechanical ventilation, inotropes, circulatory support)
- •Pregnancy
- •Ongoing enrolment in other randomized clinical trial
- •Previous randomization in DEFENDER trial
- •Active endocarditis and/or sepsis
- •Pulmonary hypertension higher than stage II (systolic pulmonary pressure over 65 mmHg according to data of preoperative transthoracic echocardiography
- •Condition after kidney transplantation
- •Ongoing AKI caused by glomerulonephritis, interstitial nephritis, renal artery occlusion, or postrenal occlusion
- •Cardiac surgery with hypothermic circulatory arrest
- •Left ventricular ejection fraction < 30%
- •Single kidney
研究组 & 干预措施
Control group
Oxygen-air mixture without NO after intubation, during CPB, and six hours after surgery.
干预措施: Sham treatment (Drug)
80-ppm NO
NO will be supplemented at 80-ppm concentration to cardiac surgery patients perioperative after trachea intubation, during CPB, and six hours after surgery.
干预措施: 80-ppm NO (Drug)
结局指标
主要结局
Incidence of AKI (%)
时间窗: 7 days
Difference between groups in the incidence of AKI in patients with CKD are assessed as percentage after cardiac surgery according to KDIGO criteria.
次要结局
- Renal replacement therapy need (%)(14 days)
- 30-day mortality rate (%)(30 days)
- ΔPCO2/ΔContO2 (ratio)(24 hours)
- Incidence of low cardiac output syndrome (%)(24 hours)
- Incidence of blood or blood component transfusion (%)(Seven days)
- AKI duration (hours)(Seven days)
- Regional tissue oxygen saturation levels (rSO2, %)(24 hours)
- Level of NO in exhaled air (ppm)(1st day after operation)
- AKI Severity (degree)(7 days)
- Duration of mechanical ventilation (hours)(21 days)
- Incidence of other postoperative complications (%)(30 days)
- Major adverse kidney events (%)(30 days)
- Incidence of incomplete recovery of renal function (%)(30 days)
- Maximum severity of multiple organ failure (SOFA scale)(24 hours)
- Vasoactive-inotropic score (VIS)(24 hours)
- ICU stay (days)(30 days)
- Hospital stay (days)(30 days)
- Hospital mortality (%)(14 days)
- Incidence of neurological complications of type 2 (delirium, early postoperative cognitive dysfunction, first-onset seizures) (%)(14 days)
- Platelet count(24 hours)
- Incidence of neurological complications of type 1 (stroke, transient ischemic attack, coma) (%)(14 days)
- Postoperative bleeding (mL)(24 hours)
- Incidence of major adverse cardiac events (MACE) (%)(30 days)
研究者
Nikolay Kamenshchikov
MD, PhD, Head of Laboratory
Tomsk National Research Medical Center of the Russian Academy of Sciences