Acute Kidney DiseasePhase 1/2DEFENDERNCT05757557
Perioperative Nitric Oxide Prevents Acute Kidney Injury in Cardiac Surgery Patients With Chronic Kidney Disease
A Phase 1/2 study testing 80-ppm NO in people with Acute Kidney Disease and Chronic Kidney Disease, run by Tomsk National Research Medical Center of the Russian Academy of Sciences at 1 site in Russia.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Kidney Disease, Chronic Kidney Disease, Cardiac Surgery
- What is being tested?
- 80-ppm NO
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 136 participants
- Where
- 1 siteRussia
- Study dates
- 25 Feb 2023to 31 Jan 2025
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 14Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
Russia1 site
Cardiology Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences
Tomsk, Russia, 634012
About this study
Official title: 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)
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
Read the detailed description
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.
Currently, there is no convincing evidence of the benefits or harms of additional NO therapy as part of the anesthesia management of cardiac surgery in patients at high risk of developing AKI. Therefore, there is no reason to believe that randomization into study groups creates additional risks/benefit for patients.
Regardless of the results of randomization, the decision on the relevance of perioperative administration of NO for cardiac surgery in each case is made by a medical consultation, including a cardiac surgeon, an anesthesiologist and a cardiologist immediately after the patient is included in the study.
The study includes patients admitted to the Cardiac Surgery Department of the Research Institute of Cardiology, Tomsk National Research Medical Center for elective surgery, and who have a high risk of AKI in the perioperative period. The frequency of AKI was chosen as the primary endpoint because the manifestation of multiple organ damage in the vast majority of cases begins with renal dysfunction. AKI is a self-perpetuating condition that causes respiratory, cardiac, and cerebral failure.
After patients enter the operating room, they are randomly assigned to the study intervention group (80 ppm NO) or control group. The devices available in the clinic, discussed above, that perform synthesis, supply of inhaled NO, and monitor NO, nitrogen dioxide (NO2) in the supply line directly during therapy, will be used NO. In the NO group, the final concentration of NO is 80 ppm. Patients in the control group will receive a standard NO-free oxygen-air mixture. NO will be supplied immediately after the patient is intubated through the anesthesia machine circuit throughout the operation, followed by the NO delivery through the oxygenator of the cardiopulmonary bypass (CPB) machine throughout the CPB, after weaning from the CPB through the anesthesia machine circuit until the end of the operation and within 6 hours after interventions through the ventilator circuit or through a face mask if the patient will be extubated earlier.
The choice of NO dose and exposure time for clinicians is based on two basic principles:
- the applied dose of NO and its exposure time are safe for patients;
- the applied dose of NO and its exposure time are sufficient to provide potential protective effects.
Devices for NO therapy (for the delivery of NO at all stages of the study) are developed at the Research and Production Center for Physics of the Federal State Unitary Enterprise "Russian Federal Nuclear Center - All-Russian Research Institute of Experimental Physics".
For the delivery of nitric oxide at all stages of the study, a device for plasma-chemical synthesis of nitric oxide will be used. For production and for all processes of the product life cycle, the International Certificate of Conformity ISO 13485:2016 Medical Devices - Quality Management Systems, No. GKRU-0072-MD has been received. The device used in this study makes it possible to produce nitric oxide from the air in a gas discharge by generating a repetitively pulsed diffuse discharge excited in an atmospheric pressure air in a gap with a sharply nonuniform electric field. Such a discharge ensures efficient synthesis of nitric oxide in a nonequilibrium low-temperature plasma.
In this study a multimodal approach will be applied to reduce the incidence of acute kidney injury after cardiac surgery. Strategies for optimizing renal outcomes will be applied during the study. Implementation of the Kidney Disease: Improving Global Outcomes guidelines for nephroprotection will be the standard for all patients during the study (Close monitoring of renal function; Functional haemodynamic monitoring; Optimizing fluid status and haemodynamics; Avoidance of hyperglycaemia; Avoidance of radiocontrast and discontinuation of nephrotoxic medications). During CPB, all patients will receive a goal-directed perfusion strategy. In this study it is aimed to maintain a high-normal oxygen delivery target at > 280 ml min m2.
Thus, this study is supposed to assess the potential benefit of perioperative NO conditioning in the era of proven technologies for preventing AKI and determine its potential relevance in the concept of multimodal protection.
- Being tested
- Sham treatment, 80-ppm NO
- Keywords
- Acute Kidney Disease, Nitric Oxide, Chronic Kidney Disease, Cardiopulmonary Bypass, Cardiac Surgery, Prevention
- Medical subject headings
- Renal Insufficiency, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sham treatmentDrug
Also called Oxygen-Air Mixture
Sham treatment: Oxygen-air mixture without NO after intubation, during CPB, and for six hours after surgery.
80-ppm NODrug
Also called Nitric Oxide
NO will be supplemented at 80-ppm concentration to cardiac surgery patients perioperatively after trachea intubation, during CPB, and for six hours after surgery.
| Study group | Role | What they receive |
|---|---|---|
| Control group | Active comparator | Oxygen-air mixture without NO after intubation, during CPB, and six hours after surgery. Receives: Drug: Sham treatment |
| 80-ppm NO | Experimental | NO will be supplemented at 80-ppm concentration to cardiac surgery patients perioperative after trachea intubation, during CPB, and six hours after surgery. Receives: Drug: 80-ppm NO |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of AKI (%)
Difference between groups in the incidence of AKI in patients with CKD are assessed as percentage after cardiac surgery according to KDIGO criteria.
Measured: 7 days
Secondary outcomes (23)
Incidence of low cardiac output syndrome (%)
Difference between groups in the incidence of low cardiac output syndrome (decrease in the incidence of low cardiac output syndrome) with the definition of its type (with dysoxia, without dysoxia, microcirculatory distress). It is a combined point and includes an increase (or various combinations of these parameters according to the cardiovascular profile in shock) of serum lactate more than 2 mmol/L, a decrease in central venous blood saturation of less than 70%, an increase in the arterio-venous carbon dioxide difference of more than 6 mm Hg, and the need for intra-aortic balloon counterpulsation or other extracorporeal methods of circulatory support within 24 hours after surgery.
Measured: 24 hours
Regional tissue oxygen saturation levels (rSO2, %)
Difference between groups in regional kidney near-infrared oximetry (rSO2, %): before sternotomy, at the CPB, 6 hours and 24 hours after surgery.
Measured: 24 hours
ΔPCO2/ΔContO2 (ratio)
Difference between groups in terms of ΔPCO2/ΔContO2: before sternotomy, 6 hours and 24 hours after surgery.
Measured: 24 hours
AKI Severity (degree)
Difference between groups in severity of AKI as defined by the KDIGO guidelines:
Stage 1 AKI is diagnosed when serum creatinine rises 1.5 to 1.9 times its baseline and preoperative values within seven days postoperatively, or when it rises ≥0.3 mg/dL (≥26.5 μm/l) within 48 hours after the intervention, and also if urine output is <0.5 ml/kg/h for 6-12 hours in the first postoperative period.
Stage 2 AKI is diagnosed when serum creatinine increases 2.0 to 2.9 times its preoperative baseline values within 7 days postoperatively and urine output is <0.5 ml/kg/h more than 12 hours after surgery.
Stage 3 AKI is diagnosed when serum creatinine rises 3 times its preoperative baseline values within seven days post-intervention, or when it rises to ≥ 4.0 mg/dl (≥ 353.6 μm/L) within 48 hours after the intervention, or if there is a need for renal replacement therapy, and also, if the urine output was <0.3 ml / kg / h within 24 hours after surgery.
Measured: 7 days
AKI duration (hours)
Difference between groups in the duration of AKI: transient (less than 48 hours) and persistent.
Measured: Seven days
Level of NO in exhaled air (ppm)
Difference between groups in the level of NO in exhaled air at baseline, on admission to the ICU, 6 hours later and 24 hours after surgery.
Measured: 1st day after operation
Renal replacement therapy need (%)
Difference between groups in the frequency of need for renal replacement therapy during hospitalization.
Measured: 14 days
Major adverse kidney events (%)
Difference between groups in the frequency of major kidney complications during hospitalization. Major adverse kidney events (MAKE) are a composite endpoint and include death, new episodes of kidney replacement therapy, and deterioration in renal function (GFR decrease of 25% or more from baseline).
Measured: 30 days
Incidence of incomplete recovery of renal function (%)
Difference between groups in the incidence of incomplete recovery of renal function (decrease in GFR by more than 10% compared with preoperative levels), or persistent renal dysfunction (defined as an increase in serum creatinine 1.5 times the baseline values or ≥0.5 mg / dL (44 µmol/L) compared with preoperative level) at discharge from the hospital.
Measured: 30 days
Maximum severity of multiple organ failure (SOFA scale)
Difference between groups in the level of organ dysfunction and mortality risk measured on a scale Sequential Organ Failure Assessment (SOFA) in the first 24 hours after surgery. Minimum score is 0, maximum score is 24. A higher score indicates an increased risk of mortality.
Measured: 24 hours
Vasoactive-inotropic score (VIS)
Difference between groups in the maximum requirement for inotropic and vasopressor drugs assessed as the vasoactive-inotropic score (VIS). VIS is calculated as follows: dose of dopamine (mcg/kg/min) + dose of dobutamine ( mcg/kg/min) + 100 x dose of epinephrine (mcg/kg/min) + 10 x dose of milrinone (mcg/kg/min) + 10,000 x dose of vasopressin (u/kg/min) + 100 x dose of norepinephrine (mcg /kg/min) + 10 × dose of phenylephrine (mcg/kg/min).
Measured: 24 hours
Duration of mechanical ventilation (hours)
Difference between groups in the duration of mechanical ventilation (hours).
Measured: 21 days
ICU stay (days)
Difference between groups in the length of ICU stay (days).
Measured: 30 days
Hospital stay (days)
Difference between groups in the length of hospital stay (days).
Measured: 30 days
Hospital mortality (%)
Difference between groups in hospital mortality rate.
Measured: 14 days
30-day mortality rate (%)
Difference between groups in mortality rate within 30 days after surgery.
Measured: 30 days
Incidence of neurological complications of type 1 (stroke, transient ischemic attack, coma) (%)
Difference between groups in the incidence of neurological complications of type 1 (stroke, transient ischemic attack, coma) during hospitalization.
Measured: 14 days
Incidence of neurological complications of type 2 (delirium, early postoperative cognitive dysfunction, first-onset seizures) (%)
Difference between groups in the incidence of neurological complications of type 2 (delirium, early postoperative cognitive dysfunction, first-onset seizures) during hospitalization.
Measured: 14 days
Platelet count
Difference between groups in platelet counts 24 hours after surgery.
Measured: 24 hours
Postoperative bleeding (mL)
Difference between groups in the volume of postoperative bleeding, which is calculated as the total blood loss through drains during the stay in the ICU.
Measured: 24 hours
Incidence of blood or blood component transfusion (%)
Difference between groups in the frequency of blood transfusion or transfusion of blood components during the period of stay in the ICU.
Measured: Seven days
Incidence of major adverse cardiac events (MACE) (%)
Differences between groups in the incidence of major adverse cardiac events (MACE) during hospitalization and within 30 days after surgery. Major adverse cardiac events - combined endpoint: myocardial infarction, pacing requirement for >48 hours, cardiac arrest.
Measured: 30 days
Incidence of other postoperative complications (%)
Differences between groups in the incidence of other postoperative complications (acute respiratory failure requiring noninvasive ventilation or reintubation, pneumonia, vasoplegia, wound infections, sepsis, readmission to the ICU) to be determined according to standard ESA/ESICM definitions where possible.
Measured: 30 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Mar 2023
- Study start25 Feb 2023
- Primary completion31 Dec 2024
- Study completion31 Jan 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Kidney DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 136 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tomsk National Research Medical Center of the Russian Academy of Sciences
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Nikolay Kamenshchikov, Tomsk National Research Medical Center of the Russian Academy of Sciences
- Investigators
- Nikolay O Kamenshchikov, MD, PhD, Principal investigator, Cardiology Research Institute, Tomsk National Research Medic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05757557
- Sponsor's protocol ID
- CRI-237
- Acronym
- DEFENDER
- Status last verified
- Oct 2026
- First submitted
- 11 Feb 2023
- Last updated
- 23 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Deidentified individual participant data (text, tables, figures, and appendices), underlying the results of the trial, will be shared with researchers to achieve the aims in the approved proposal
Study at a glance
From the registry record, last updated by the sponsor on 23 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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)
- ClinicalTrials.gov ID
- NCT05757557
- Acronym / sponsor ID
- DEFENDER / CRI-237
- Keywords
- Acute Kidney Disease, Nitric Oxide, Chronic Kidney Disease, Cardiopulmonary Bypass, Cardiac Surgery, Prevention
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 136 participants (actual)
- Lead sponsor
- Tomsk National Research Medical Center of the Russian Academy of SciencesUniversity, hospital or other
- Study start
- 25 Feb 2023 (actual)
- Primary completion
- 31 Dec 2024 (actual)
- Study completion
- 31 Jan 2025 (actual)
- First posted
- 7 Mar 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Detailed description
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.
Currently, there is no convincing evidence of the benefits or harms of additional NO therapy as part of the anesthesia management of cardiac surgery in patients at high risk of developing AKI. Therefore, there is no reason to believe that randomization into study groups creates additional risks/benefit for patients.
Regardless of the results of randomization, the decision on the relevance of perioperative administration of NO for cardiac surgery in each case is made by a medical consultation, including a cardiac surgeon, an anesthesiologist and a cardiologist immediately after the patient is included in the study.
The study includes patients admitted to the Cardiac Surgery Department of the Research Institute of Cardiology, Tomsk National Research Medical Center for elective surgery, and who have a high risk of AKI in the perioperative period. The frequency of AKI was chosen as the primary endpoint because the manifestation of multiple organ damage in the vast majority of cases begins with renal dysfunction. AKI is a self-perpetuating condition that causes respiratory, cardiac, and cerebral failure.
After patients enter the operating room, they are randomly assigned to the study intervention group (80 ppm NO) or control group. The devices available in the clinic, discussed above, that perform synthesis, supply of inhaled NO, and monitor NO, nitrogen dioxide (NO2) in the supply line directly during therapy, will be used NO. In the NO group, the final concentration of NO is 80 ppm. Patients in the control group will receive a standard NO-free oxygen-air mixture. NO will be supplied immediately after the patient is intubated through the anesthesia machine circuit throughout the operation, followed by the NO delivery through the oxygenator of the cardiopulmonary bypass (CPB) machine throughout the CPB, after weaning from the CPB through the anesthesia machine circuit until the end of the operation and within 6 hours after interventions through the ventilator circuit or through a face mask if the patient will be extubated earlier.
The choice of NO dose and exposure time for clinicians is based on two basic principles:
- the applied dose of NO and its exposure time are safe for patients;
- the applied dose of NO and its exposure time are sufficient to provide potential protective effects.
Devices for NO therapy (for the delivery of NO at all stages of the study) are developed at the Research and Production Center for Physics of the Federal State Unitary Enterprise "Russian Federal Nuclear Center - All-Russian Research Institute of Experimental Physics".
For the delivery of nitric oxide at all stages of the study, a device for plasma-chemical synthesis of nitric oxide will be used. For production and for all processes of the product life cycle, the International Certificate of Conformity ISO 13485:2016 Medical Devices - Quality Management Systems, No. GKRU-0072-MD has been received. The device used in this study makes it possible to produce nitric oxide from the air in a gas discharge by generating a repetitively pulsed diffuse discharge excited in an atmospheric pressure air in a gap with a sharply nonuniform electric field. Such a discharge ensures efficient synthesis of nitric oxide in a nonequilibrium low-temperature plasma.
In this study a multimodal approach will be applied to reduce the incidence of acute kidney injury after cardiac surgery. Strategies for optimizing renal outcomes will be applied during the study. Implementation of the Kidney Disease: Improving Global Outcomes guidelines for nephroprotection will be the standard for all patients during the study (Close monitoring of renal function; Functional haemodynamic monitoring; Optimizing fluid status and haemodynamics; Avoidance of hyperglycaemia; Avoidance of radiocontrast and discontinuation of nephrotoxic medications). During CPB, all patients will receive a goal-directed perfusion strategy. In this study it is aimed to maintain a high-normal oxygen delivery target at > 280 ml min m2.
Thus, this study is supposed to assess the potential benefit of perioperative NO conditioning in the era of proven technologies for preventing AKI and determine its potential relevance in the concept of multimodal protection.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Control group | Active comparator | Drug: Sham treatmentOxygen-air mixture without NO after intubation, during CPB, and six hours after surgery. |
| 80-ppm NO | Experimental | Drug: 80-ppm NONO will be supplemented at 80-ppm concentration to cardiac surgery patients perioperative after trachea intubation, during CPB, and six hours after surgery. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (14 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Sham treatmentAlso: Oxygen-Air MixtureSham treatment: Oxygen-air mixture without NO after intubation, during CPB, and for six hours after surgery. | Drug | Control group |
| 80-ppm NOAlso: Nitric OxideNO will be supplemented at 80-ppm concentration to cardiac surgery patients perioperatively after trachea intubation, during CPB, and for six hours after surgery. | Drug | 80-ppm NO |
Primary outcome
Incidence of AKI (%)
Time frame: 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.
23 secondary outcomes
Incidence of low cardiac output syndrome (%)
Time frame: 24 hours
Regional tissue oxygen saturation levels (rSO2, %)
Time frame: 24 hours
ΔPCO2/ΔContO2 (ratio)
Time frame: 24 hours
AKI Severity (degree)
Time frame: 7 days
AKI duration (hours)
Time frame: Seven days
Level of NO in exhaled air (ppm)
Time frame: 1st day after operation
Renal replacement therapy need (%)
Time frame: 14 days
Major adverse kidney events (%)
Time frame: 30 days
Incidence of incomplete recovery of renal function (%)
Time frame: 30 days
Maximum severity of multiple organ failure (SOFA scale)
Time frame: 24 hours
Vasoactive-inotropic score (VIS)
Time frame: 24 hours
Duration of mechanical ventilation (hours)
Time frame: 21 days
ICU stay (days)
Time frame: 30 days
Hospital stay (days)
Time frame: 30 days
Hospital mortality (%)
Time frame: 14 days
30-day mortality rate (%)
Time frame: 30 days
Incidence of neurological complications of type 1 (stroke, transient ischemic attack, coma) (%)
Time frame: 14 days
Incidence of neurological complications of type 2 (delirium, early postoperative cognitive dysfunction, first-onset seizures) (%)
Time frame: 14 days
Platelet count
Time frame: 24 hours
Postoperative bleeding (mL)
Time frame: 24 hours
Incidence of blood or blood component transfusion (%)
Time frame: Seven days
Incidence of major adverse cardiac events (MACE) (%)
Time frame: 30 days
Incidence of other postoperative complications (%)
Time frame: 30 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Oct 2026.
- Individual participant dataSharing planned: Yes. Deidentified individual participant data (text, tables, figures, and appendices), underlying the results of the trial, will be shared with researchers to achieve the aims in the approved proposal
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Nikolay O Kamenshchikov, MD, PhD principal investigator
Cardiology Research Institute, Tomsk National Research Medic
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing 80-ppm NO in people with Acute Kidney Disease and Chronic Kidney Disease, run by Tomsk National Research Medical Center of the Russian Academy of Sciences at 1 site in Russia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Russia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of AKI (%) (time frame: 7 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Oct 2026.