Nitric Oxide in Cardiopulmonary Bypass for Renal Protection in Cardiac Surgery

Coronary Artery Disease Clinical Trial

— NephroNO  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03527381
• Other study ID #: NephroNO
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: September 1, 2015
• Est. completion date: April 14, 2017

Study information

• Verified date: January 2020
• Source: Tomsk National Research Medical Center of the Russian Academy of Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 96
• Est. completion date: April 14, 2017
• Est. primary completion date: December 25, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Acute Kidney Injury
• Cardiomyopathies
• Coronary Artery Disease
• Heart Valve Diseases

Intervention

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

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

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Nikolay Kamenshchikov

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Secondary	Urine output measure	Urine output values (mL/kg/h) are assessed during cardiopulmonary bypass (CPB).	During cardiopulmonary bypass
Secondary	Urine neutrophil gelatinase-associated lipocalin concentration measure (uNGAL)	The level of uNGAL (ng/mL) is assessed 4 hours after the surgery.	4 hours after surgery
Secondary	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
Secondary	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
Secondary	Proinflammatory mediator concentration measure	Concentrations of proinflammatory (TNF-a, IL-1ß, -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
Secondary	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