Cardiac Surgery Associated - Acute Kidney Injury, Cardiac Surgery With Cardiopulmonary Bypass
Conditions
Keywords
Acute Kidney Injury, Nitric Oxide, Cardiac surgery, Cardiopulmonary Bypass, Randomized Controlled Trial
Brief summary
The goal of this clinical trial is to learn if giving inhaled nitric oxide during heart surgery can prevent acute kidney injury (AKI) in patients who are at high risk of developing this complication. AKI is a serious problem after heart surgery and can lead to longer hospital stays, higher costs, and increased risk of death or long-term kidney disease. Currently, there is no effective medicine to prevent AKI after heart surgery. The main questions it aims to answer are: * Does inhaled nitric oxide reduce the chance of developing AKI within 7 days after heart surgery compared to placebo? * Does inhaled nitric oxide help preserve kidney function up to 90 days after surgery? Researchers will compare inhaled nitric oxide (the device is turned on) to a placebo (the same device is connected to the breathing circuit but not turned on, so no nitric oxide is given). The device panel is covered so that both participants and the research team do not know who receives active treatment or placebo (double-blind). Participants in this study will: * Have the nitric oxide device connected to their breathing circuit during heart surgery; they will receive either active nitric oxide or no nitric oxide (device off) * Provide blood and urine samples to test kidney function during and after surgery * Be followed for 90 days after surgery to monitor kidney health and any side effects
Detailed description
This is a single-center, prospective, randomized, double-blind, placebo-controlled superiority trial. It evaluates whether intraoperative inhaled nitric oxide (iNO) at 80 ppm reduces the incidence of acute kidney injury (AKI) within 7 days after cardiac surgery with cardiopulmonary bypass (CPB) in high-risk patients (Mayo Clinic renal risk score ≥2). Intervention: Patients receive inhaled nitric oxide at 80 ppm via the ventilator circuit during CPB and until the end of surgery. Control: The same device is connected but remains turned off (no iNO delivery). The device screen is covered in both groups to maintain blinding. Randomization and blinding: Randomization (1:1) uses a blocked scheme with allocation concealment. Patients, surgeons, anesthesiologists, ICU staff, and outcome assessors are blinded. A dedicated gas therapist (not otherwise involved) manages the device. Standardized management: All patients receive standardized anesthesia, CPB, and KDIGO-recommended AKI prevention bundle (MAP\>55 mmHg, goal-directed perfusion). Safety monitoring: Intraoperative methemoglobin (blood gas) and nitrogen dioxide (device readout) are monitored with predefined safety thresholds for dose adjustment. Exploratory biomarker substudy (optional): Blood and urine samples are collected at perioperative time points to measure biomarkers of kidney injury and inflammation. Follow-up: In-hospital outcomes (complications, ventilation duration, length of stay) and telephone follow-up at 30 and 90 days for major adverse kidney and cardiovascular events. Sample size: Approximately 330 participants (1:1) are planned. Statistical analysis: The primary analysis compares 7-day AKI incidence between groups with a two-sided α=0.05. Secondary outcomes will be analyzed using appropriate parametric or non-parametric methods.
Interventions
Inhaled nitric oxide(iNO) at 80 ppm is delivered via the ventilator circuit during cardiopulmonary bypass and until the end of surgery. The gas is administered using the INOwill N200 delivery device (which is turned ON).
DRUGPlacebo
The same NO device is connected to the ventilator circuit but remains TURNED OFF, so no nitric oxide is delivered. The device screen is covered to maintain blinding. Participants in the placebo group receive no active drug.
Sponsors
Shanghai Zhongshan Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
The gas therapist who operates and adjusts the nitric oxide(NO) delivery device is unblinded. All other parties including patients, surgeons, anesthesiologists, ICU staff, outcome assessors, and data analysts are blinded. The device screen is covered with an opaque material in both the active and placebo groups to maintain blinding. The unblinded gas therapist does not participate in any other study procedures (e.g., patient management, data collection, or outcome assessment).
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥18 years * Scheduled for elective cardiac surgery with cardiopulmonary bypass, including valve surgery and/or coronary artery bypass grafting (CABG) * Mayo Clinic renal risk score ≥2
Exclusion criteria
* Emergency surgery * Cardiac or major vascular surgery requiring deep hypothermic circulatory arrest * Use of potentially nephrotoxic drugs (e.g., radiocontrast agents, aminoglycosides, amphotericin) within 24 hours before surgery * Preoperative heart failure or low cardiac output syndrome requiring life support devices (ECMO, Impella or other left ventricular assist devices, mechanical ventilation), or left ventricular ejection fraction \<30%, or other equivalent severe cardiac dysfunction * Receipt of inhaled nitric oxide or inhaled prostacyclin within 7 days before randomization * End-stage renal disease with eGFR \<15 mL/min, or currently receiving renal replacement therapy, or prior kidney transplantation * Hemophilia A or B * Other end-stage chronic disease with estimated life expectancy \<1 year (as assessed by the attending physician) * Pregnancy * Active endocarditis or other active infection
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Acute Kidney Injury (AKI) within 7 Days After Surgery | Up to 7 days after surgery | Proportion of participants developing AKI within 7 days post-surgery, defined according to the KDIGO 2012 criteria. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| AKI Stage and Duration | Up to 7 days after surgery | Maximum KDIGO stage (1, 2, or 3) of AKI and total duration (days) of AKI during the first 7 postoperative days. |
| Major Adverse Kidney Events (MAKE) | At hospital discharge, and at 30 days and 90 days after surgery | Composite of all-cause death, new need for renal replacement therapy, or a ≥25% decline in eGFR from baseline. Assessed during hospital stay and at 30 and 90 days after discharge. |
| Major Adverse Cardiovascular Events (MACE) | At hospital discharge, and at 30 days and 90 days after surgery | Composite of myocardial infarction, stroke, or all-cause death. Assessed during hospital stay and at 30 and 90 days after discharge. |
| Postoperative Complications | From end of surgery until hospital discharge (assessed up to 90 days) | Occurrence of pneumonia, stroke, myocardial infarction, or other major complications during the postoperative hospital stay. |
| Duration of Mechanical Ventilation | During intensive care unit (ICU) stay, up to 30 days | Total time (hours) from end of surgery until successful extubation. |
| ICU Length of Stay | During hospitalization, up to 90 days | Total number of days from ICU admission to ICU discharge. |
| Hospital Length of Stay | During hospitalization, up to 90 days | Total number of days from surgery to hospital discharge. |
Countries
China
Contacts
CONTACTKefang Guo, M.D.
CONTACTYing Yu, M.D.
PRINCIPAL_INVESTIGATORKefang Guo, M.D.
Zhongshan hospital, Fudan university,Shanghai, China
Outcome results
None listed