Clinical trial NCT03527381: Nitric Oxide in Cardiopulmonary Bypass for Renal Protection in Cardiac Surgery
Official title: Nitric Oxide Supplementation to the Extracorporeal Circulation Line as a Method of Nephroprotection in Cardiac Surgery
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Coronary Artery Disease
Heart Valve Diseases
Cardiomyopathies
Acute Kidney Injury
Keywords: Cardiopulmonary Bypass
Nitric Oxide
Kidney Function Tests
Renal Insufficiency
Protective Agents
Coronary Artery Bypass
Cardiac Surgery
Lead sponsor: Tomsk National Research Medical Center of the Russian Academy of Sciences
Sponsor class: OTHER
First posted: 2018-05-17
Enrollment: 96
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Single-center prospective, randomized, placebo-controlled study
Primary purpose: PREVENTION

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

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Acute kidney injury rate measure
timeFrame: 48 hours after surgery
Secondary outcomes:
measure: Urine output measure
timeFrame: During cardiopulmonary bypass
measure: Urine neutrophil gelatinase-associated lipocalin concentration measure (uNGAL)
timeFrame: 4 hours after surgery
measure: Free hemoglobin (Hb) concentration measure
timeFrame: 24 hours after surgery
measure: Nitric oxide metabolite concentration measure
timeFrame: 24 hours after surgery
measure: Proinflammatory mediator concentration measure
timeFrame: 24 hours after surgery
measure: Anti-inflammatory mediator concentration measure
timeFrame: 24 hours after surgery
Other outcomes:
Locations:
Study officials:
affiliation: Tomsk NRMC
name: Sergey V. Popov, MD, PhD
role: STUDY_DIRECTOR
References:
citation: 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.