Inhaled Nitric Oxide for Prevention of Postoperative AKI in High-Risk Cardiac Surgery Patients

Официальное название

Intraoperative Inhaled Nitric Oxide to Reduce Postoperative Acute Kidney Injury in High-Risk Patients Undergoing Cardiac Surgery With Cardiopulmonary Bypass

Обзор

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

Подробное описание

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.

Вмешательства

• Препарат Inhaled Nitric Oxide (iNO)
  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).
• Препарат Placebo
  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.

Первичные конечные точки

• Incidence of Acute Kidney Injury (AKI) within 7 Days After Surgery [Срок оценки: Up to 7 days after surgery]

Вторичные конечные точки (7)

• AKI Stage and Duration [Срок оценки: Up to 7 days after surgery]
• Major Adverse Kidney Events (MAKE) [Срок оценки: At hospital discharge, and at 30 days and 90 days after surgery]
• Major Adverse Cardiovascular Events (MACE) [Срок оценки: At hospital discharge, and at 30 days and 90 days after surgery]
• Postoperative Complications [Срок оценки: From end of surgery until hospital discharge (assessed up to 90 days)]
• Duration of Mechanical Ventilation [Срок оценки: During intensive care unit (ICU) stay, up to 30 days]
• ICU Length of Stay [Срок оценки: During hospitalization, up to 90 days]
• Hospital Length of Stay [Срок оценки: During hospitalization, up to 90 days]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Профилактика

Центры проведения

Китай · 1 центр

• Zhongshan Hospital, Fudan University — Шанхай

Идентификаторы

NCT: NCT07544147 · B2026-171

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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