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NCT Number: NCT03527381

Nitric Oxide in Cardiopulmonary Bypass for Renal Protection in Cardiac Surgery

This prospective randomized study evaluates the nephroprotective effects of exogenous nitric oxide delivered to the extracorporeal circulation circuit during cardiac surgery with cardiopulmonary bypass.

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Key information

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

nitric oxide

Drug

40 ppm of exogenous gaseous nitric oxide is supplied directly to the oxygenator in the cardiopulmonary bypass circuit during cardiac surgery.

Standard CPB

Other

Standard CPB protocol of delivery of air gas mixture to the cardiopulmonary bypass circuit during cardiac surgery.

Primary outcomes

  1. Acute kidney injury rate measure

    Time frame: 48 hours after surgery

    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.

Secondary outcomes

  1. Urine output measure

    Time frame: During cardiopulmonary bypass

    Urine output values (mL/kg/h) are assessed during cardiopulmonary bypass (CPB).

  2. Urine neutrophil gelatinase-associated lipocalin concentration measure (uNGAL)

    Time frame: 4 hours after surgery

    The level of uNGAL (ng/mL) is assessed 4 hours after the surgery.

  3. Free hemoglobin (Hb) concentration measure

    Time frame: 24 hours after surgery

    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.

  4. Nitric oxide metabolite concentration measure

    Time frame: 24 hours after surgery

    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.

  5. Proinflammatory mediator concentration measure

    Time frame: 24 hours after surgery

    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.

  6. Anti-inflammatory mediator concentration measure

    Time frame: 24 hours after surgery

    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.

Sponsors and collaborators

Lead sponsor

Nikolay Kamenshchikov

Other

Registry information

Official study title

Nitric Oxide Supplementation to the Extracorporeal Circulation Line as a Method of Nephroprotection in Cardiac Surgery

Acronym: NephroNO

Important dates

Study start
2015
Primary completion
2016
Study completion
2017
First posted
May 17, 2018
Registry last updated
Jan 23, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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