Randomized, Controlled, Double-blinded Pilot Study: Nitrite Infusion in High Risk Patients Undergoing Cardiopulmonary Bypass
试验速览
- 阶段
- 3 期
- 状态
- 撤回
- 试验地点
- 1
- 主要终点
- Nitrite Metabolome Levels
研究概览
简要总结
The main objective of this study is to evaluate the efficacy of intravenous sodium nitrite compared with placebo in reducing the occurrence of CSA-AK as diagnosed by KDIGO criteria during the first 72 hrs after cardiac surgery in high-risk patients undergoing cardiac surgery. Secondary objectives are to determine whether IV sodium nitrite achieves adequate pharmacokinetics (PK) in patients undergoing cardiac surgery with the use of CPB.
详细描述
Acute kidney injury is one of the most untoward consequences of cardiac-surgery with the use of CPB. As such it is associated with a high mortality and morbidity and health care expense. Unfortunately, currently, there is no effective preventive or treatment strategy for cardiac surgery-associated (CSA) AKI other than renal replacement therapy.
It is postulated that a major mechanism of CSA-AKI is created by the ischemia reperfusion injury (IRI) resulting from aortic cross clamping and unclamping. This creates a cascade of events culminating in inflammation, microvascular dysfunction and tubular cell maladaptation and eventually renal tissue damage. Current treatment modalities that target the microcirculation such as blood pressure and cardiac output fails to prevent renal abnormalities and as such may be deleterious to the renal tissue microcirculation. The PI hypothesizes that a therapeutic strategy that limits IRI such as the administration of inhaled nitric oxide (NO) or sodium nitrite (NaNO2) would ameliorate CSA-AKI by limiting inflammatory injury to the kidney.
The anion nitrite (NO2-) releases NO in biological systems and has been demonstrated to inhibit IR injury in the heart, liver and kidneys created by various pathologic states1-3 and improve outcomes in patients with acute myocardial infarction, in patients with pulmonary hypertension and is the putative active mediator of protection in liver-transplantation patients receiving inhaled nitric oxide4.
The objective of this study is to determine whether the NO donor, nitrite will prevent I/R injury in patients at high risk of development of CSA-AKI undergoing open-heart surgery with cardiopulmonary bypass.
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, Investigator)
入排标准
- 年龄范围
- 19 Years 至 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Patients CCFS score ≥ 6 (Table 1)
- •Patients admitted to UAB cardiac intensive care unit (CICU) following elective cardiac surgery with cardiopulmonary bypass under general endotracheal anesthesia
- •19 years old
- •Estimated glomerular filtration rate (eGFR) ≥ 30 ml/min/1.73 m2
排除标准
- •Prisoners directly admitted from a correctional facility.
- •Children < 19 years or under 50 kg body weight if age is unknown.
- •Patients enrolled in a concurrent ongoing interventional, randomized clinical trial.
- •Patients with end stage renal disease or preexisting GFR <30 mL/min/1.73 m2 or need for dialysis. 34
- •Patients with end stage heart disease on the cardiac transplant list.
- •Patients undergoing procedures without the use of CPB
- •All transplant patients.
- •Patients on ventricular assist devices.
- •Patients undergoing emergency procedures.
- •Patients with glucose 6-dehydrogenase deficiency
- •Pregnancy
研究组 & 干预措施
Control group
saline infusion will be administered after induction of general anesthesia
干预措施: Saline (Drug)
Control group
saline infusion will be administered after induction of general anesthesia
干预措施: Sodium Nitrite (Drug)
Sodium Nitrite
sodium nitrite will start after induction of general anesthesia via a dedicated IV line for 6 hrs.
干预措施: Saline (Drug)
Sodium Nitrite
sodium nitrite will start after induction of general anesthesia via a dedicated IV line for 6 hrs.
干预措施: Sodium Nitrite (Drug)
结局指标
主要结局
Nitrite Metabolome Levels
时间窗: baseline to 73 hrs post-operatively
Measuring nitrite, nitrate, and nitrosothiols levels
Biomarkers of Hemolysis
时间窗: baseline to 73 hrs post-operatively
Measuring hemolysis indicators heme, Hb, hemopexin, and hemopectin
Biomarkers of Kidney Injury
时间窗: baseline to 73 hrs post-operatively
Measuring kidney injury indicators creatine, neutrophil-associated gelatinase, lipocalin (NGAL)
Cell Cycle Stress
时间窗: baseline to 73 hrs post-operatively
Measuring cell cycle arrest biomarkers TIMP-2, IGFBP-7
次要结局
- Vasopressors Usage(baseline to 73 hrs post-operatively)
- Biomarkers of Myocardial Injury(baseline to 24 hours post-operatively)
- Urine Output(baseline to 73 hrs post-operatively)
- Biomarkers of Kidney Injury(baseline to 24 hours post-operatively)
- Cell Cycle Stress(baseline to 24 hours post-operatively)
- Biomarkers of Hepatic injury(baseline to 24 hours post-operatively)
研究者
Ahmed Zaky
Associate Professor
University of Alabama at Birmingham