An interventional study of Inhaled Nitric Oxide (iNO) and Placebo in Cardiac Surgery Associated - Acute Kidney Injury and Cardiac Surgery With Cardiopulmonary Bypass, sponsored by Shanghai Zhongshan Hospital. Not yet recruiting at 1 site in China. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-04-22.
Sponsored by Shanghai Zhongshan Hospital · Not applicable, Interventional, and Prevention
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:
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:
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.
1,594 studies on the registry are indexed under Acute Kidney Injury; 370 are open to participants now.
This study's planned enrollment of 330 is above the median of 100 across 763 interventional studies indexed under Acute Kidney Injury.
Browse Acute Kidney Injury studies →Shanghai Zhongshan Hospital is the lead sponsor of 636 studies on the registry; 283 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Drug: Inhaled Nitric Oxide (iNO)
Drug: Placebo
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).
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.
Incidence of Acute Kidney Injury (AKI) within 7 Days After Surgery
Proportion of participants developing AKI within 7 days post-surgery, defined according to the KDIGO 2012 criteria.
Time frame: Up to 7 days after surgery
AKI Stage and Duration
Maximum KDIGO stage (1, 2, or 3) of AKI and total duration (days) of AKI during the first 7 postoperative days.
Time frame: Up to 7 days after surgery
Major Adverse Kidney Events (MAKE)
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.
Time frame: At hospital discharge, and at 30 days and 90 days after surgery
Major Adverse Cardiovascular Events (MACE)
Composite of myocardial infarction, stroke, or all-cause death. Assessed during hospital stay and at 30 and 90 days after discharge.
Time frame: At hospital discharge, and at 30 days and 90 days after surgery
Postoperative Complications
Occurrence of pneumonia, stroke, myocardial infarction, or other major complications during the postoperative hospital stay.
Time frame: From end of surgery until hospital discharge (assessed up to 90 days)
Duration of Mechanical Ventilation
Total time (hours) from end of surgery until successful extubation.
Time frame: During intensive care unit (ICU) stay, up to 30 days
ICU Length of Stay
Total number of days from ICU admission to ICU discharge.
Time frame: During hospitalization, up to 90 days
Hospital Length of Stay
Total number of days from surgery to hospital discharge.
Time frame: During hospitalization, up to 90 days
Intraoperative Methemoglobin Level
Maximum methemoglobin level (%) measured by intraoperative blood gas analysis.
Time frame: During surgery (from induction until sternal closure)
Nitrogen Dioxide Level
Maximum nitrogen dioxide level (ppm) measured in real time by the NO delivery device.
Time frame: During surgery (from start of iNO delivery until end of surgery)
Dose Reduction or Discontinuation of Study Gas
Number of participants in whom the study gas was reduced or stopped because methemoglobin exceeded 5% or nitrogen dioxide exceeded 3 ppm.
Time frame: During surgery (from start of iNO delivery until end of surgery)
Adverse Events Related to Study Gas Administration
Any adverse event that leads to early discontinuation or prolonged use of the study gas, including worsening oxygenation, elevated pulmonary artery pressure causing hypoxemia, systemic hypotension, bradycardia, or right heart failure.
Time frame: During surgery (from start of iNO delivery until end of surgery)
Urinary NGALLevels
Urinary neutrophil gelatinase-associated lipocalin (NGAL) measured at baseline (pre-anesthesia induction) and at 6, 24, and 72 hours after surgery.
Time frame: Preoperative (baseline) and postoperative hours 6, 24, 72
Urinary KIM-1 Level
Urinary kidney injury molecule-1 (KIM-1) measured at baseline (pre-anesthesia induction) and at 6, 24, and 72 hours after surgery.
Time frame: Preoperative (baseline) and postoperative hours 6, 24, 72
Serum Cystatin C Level
Serum cystatin C (mg/L) measured at baseline and at 6, 24, and 72 hours after surgery.
Time frame: Preoperative (baseline) and postoperative hours 6, 24, 72
Inflammatory Cytokine Levels
Serum levels (pg/mL) of inflammatory cytokines (e.g., interleukin-1 \[IL-1\], IL-2, IL-6, IL-18, and tumor necrosis factor-alpha \[TNF-α\]) measured at baseline and at 6, 24, and 72 hours after surgery.
Time frame: Preoperative (baseline) and postoperative hours 6, 24, 72
Plan to share: No — The investigators do not plan to share individual participant data (IPD). The informed consent form signed by participants did not include provisions for sharing de-identified data with external researchers beyond the primary study team.
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Shanghai Zhongshan Hospital