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This prospective randomized study evaluates the nephroprotective effects of exogenous nitric oxide delivered to the extracorporeal circulation circuit during cardiac surgery with cardiopulmonary bypass.
The aim of this work is to study nephroprotective effects of nitric oxide (NO) supplementation to the cardiopulmonary bypass (CPB) circuit during cardiac surgery with normothermic CPB in adult patients. The prospective randomized study is performed in the settings of Federal Cardiology Center. A total of 96 adult patients who underwent cardiac surgery with CPB are enrolled in the study. Patients are randomized to two groups: main group receive NO treatment; control group undergoes sham procedure. In the main group, NO is supplied to the CPB line in a dose of 40 ppm throughout the entire CPB period. The primary endpoint is the frequency of acute kidney injury (AKI). The secondary endpoints are urine output during CPB; uNGAL level 4 h after surgery; plasma concentration of free hemoglobin (Hb); concentrations of NO metabolites (nitrite (NO2-) and nitrate (NO3-)) and the total concentration of metabolites of NO (NOx, μM/mL) in blood plasma in the intraoperative period; concentration of proinflammatory (TNF-α, IL-1β, -6, and -8) and anti-inflammatory mediators (IL-1ra, IL-4) in blood plasma in the intraoperative period. Cumulative fluid balance, diuresis, and Lasix doses are assessed within the first 48 h of the postoperative period. The dynamics of serum creatinine is assessed during the first week following the intervention.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Nitric Oxide | Experimental | Patients of this group receive treatment with exogenous gaseous nitric oxide supplied directly to the oxygenator in the cardiopulmonary bypass circuit during cardiac surgery. |
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| Standard CPB | Placebo Comparator | Patients of this group receive sham-treatment without supplying nitric oxide to the cardiopulmonary bypass circuit (Standard CPB) during cardiac surgery. Considering dilution of nitric oxide at a high ratio of 1 to 25,000 in the gas mixture of the cardiopulmonary bypass circuit (CPB), no addition of any inert gas to the CPB circuit is required in sham-treatment group. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Nitric Oxide | Drug | 40 ppm of exogenous gaseous nitric oxide is supplied directly to the oxygenator in the cardiopulmonary bypass circuit during cardiac surgery. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Acute kidney injury rate measure | The presence of acute kidney injury (AKI) is assessed during 48 hours after surgery. AKI is defined as follows: an increase in serum creatinine ≥ 0.3 mg/dL (≥ 26.5 μM/L) during 48 hours after surgery; an increase in serum creatinine by ≥ 1.5 times compared with the initial preoperative level for seven days after intervention; and urine output < 0.5 mL/kg/h for 6 hours during the first 48 h after surgery. | 48 hours after surgery |
| Measure | Description | Time Frame |
|---|---|---|
| Urine output measure | Urine output values (mL/kg/h) are assessed during cardiopulmonary bypass (CPB). | During cardiopulmonary bypass |
| Urine neutrophil gelatinase-associated lipocalin concentration measure (uNGAL) |
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Inclusion Criteria:
Age above 18 years; planned primary cardiac intervention with cardiopulmonary bypass including coronary artery bypass grafting, valve surgery, and surgical reconstructions of the left ventricle.
Exclusion Criteria:
Preoperative anemia; the intake of nephrotoxic drugs or the use of X-ray contrast within 72 h before surgery; active phase of endocarditis; emergency surgery; chronic kidney disease; hematologic diseases accompanied by hemolysis; complications of the surgery and the early postoperative period.
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| Name | Affiliation | Role |
|---|---|---|
| Sergey V. Popov, MD, PhD | Tomsk NRMC | Study Director |
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32718702 | Derived | Kamenshchikov NO, Anfinogenova YJ, Kozlov BN, Svirko YS, Pekarskiy SE, Evtushenko VV, Lugovsky VA, Shipulin VM, Lomivorotov VV, Podoksenov YK. Nitric oxide delivery during cardiopulmonary bypass reduces acute kidney injury: A randomized trial. J Thorac Cardiovasc Surg. 2022 Apr;163(4):1393-1403.e9. doi: 10.1016/j.jtcvs.2020.03.182. Epub 2020 Jun 25. |
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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.
Proposals may be submitted up to 36 months following publication of the results of the trial. After 36 months, the data will be available in the Center's data ware house but without investigator support other than deposited metadata.
Information regarding submitting proposals and accessing data may be requested from the principal investigator by e-mail.
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| ID | Term |
|---|---|
| D003324 | Coronary Artery Disease |
| D006349 | Heart Valve Diseases |
| D009202 | Cardiomyopathies |
| D058186 | Acute Kidney Injury |
| D051437 | Renal Insufficiency |
| ID | Term |
|---|---|
| D003327 | Coronary Disease |
| D017202 | Myocardial Ischemia |
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
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| ID | Term |
|---|---|
| D009569 | Nitric Oxide |
| ID | Term |
|---|---|
| D026361 | Reactive Nitrogen Species |
| D005609 | Free Radicals |
| D007287 | Inorganic Chemicals |
| D009589 | Nitrogen Oxides |
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Single-center prospective, randomized, placebo-controlled study
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Trial participants, data analysts, and report writers are blinded.
| Standard CPB | Other | Standard CPB protocol of delivery of air gas mixture to the cardiopulmonary bypass circuit during cardiac surgery. |
|
The level of uNGAL (ng/mL) is assessed 4 hours after the surgery.
| 4 hours after surgery |
| Free hemoglobin (Hb) concentration measure | Plasma concentrations of Hg (g/L) are assessed during intraoperative period: before sternotomy, 5 minutes after aortic clamping, 5 minutes after aortic declamping, at the end of surgery, and 24 hours after surgery. | 24 hours after surgery |
| Nitric oxide metabolite concentration measure | Concentrations of NO metabolites (nitrite (NO2-) and nitrate (NO3-)) (μM/mL) and the total concentration of metabolites of NO (NOx) (μM/mL) in blood plasma are assessed in the intraoperative period: before sternotomy, 5 minutes after aortic clamping, 5 minutes after aortic declamping, at the end of surgery, and 24 hours after surgery. | 24 hours after surgery |
| Proinflammatory mediator concentration measure | Concentrations of proinflammatory (TNF-α, IL-1β, -6, and -8) (pg/mL) in blood plasma are assessed in the intraoperative period: before sternotomy, at the end of surgery, 6 hours after surgery, and 24 hours after surgery. | 24 hours after surgery |
| Anti-inflammatory mediator concentration measure | Concentrations of anti-inflammatory mediators (IL-1ra, IL-4) (pg/mL) in blood plasma are assessed in the intraoperative period: before sternotomy, at the end of surgery, 6 hours after surgery, and 24 hours after surgery. | 24 hours after surgery |
| D001161 |
| Arteriosclerosis |
| D001157 | Arterial Occlusive Diseases |
| D014652 | Vascular Diseases |
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| D017672 |
| Nitrogen Compounds |
| D010087 | Oxides |
| D017601 | Oxygen Compounds |
| D009930 | Organic Chemicals |