Nitric Oxide in Cardiopulmonary Bypass for Renal Protection in Cardiac Surgery (NephroNO)

Nikolay Kamenshchikov

Status and phase: Completed; Phase 2; Phase 1

Conditions: Heart Valve Diseases; Coronary Artery Disease; Acute Kidney Injury; Cardiomyopathies

Treatments: Other: Standard CPB; Drug: Nitric Oxide

Study type: Interventional

Funder types: Other

Identifiers

NCT03527381

NephroNO

Details and patient eligibility

About

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

Full description

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.

Enrollment: 96 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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96 participants in 2 patient groups, including a placebo group

Nitric Oxide

Experimental group

Description:

Patients of this group receive treatment with exogenous gaseous nitric oxide supplied directly to the oxygenator in the cardiopulmonary bypass circuit during cardiac surgery.

Treatment:

Drug: Nitric Oxide

Standard CPB

Placebo Comparator group

Description:

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.

Treatment:

Other: Standard CPB