NO During CPB in Neonates to Reduce Risk of AKI

Efficacy of Nitric Oxide Administration During Cardiopulmonary Bypass in Neonates at Reducing the Risk of Acute Kidney Injury

Acute kidney injury (AKI) following cardiac surgery for congenital heart defects (CHD) in children affects up to 60% of high risk-patients and is a major cause of both short- and long-term morbidity and mortality. Despite effort, to date, no successful therapeutic agent has gained widespread success in preventing this postoperative decline in renal function. Nitric oxide is an intricate regulator of acute inflammation and coagulation and is a potent vasodilator. The investigators hypothesize that nitric oxide, administered during cardiopulmonary bypass (CPB), may reduce the incidence of AKI.

Study Overview

• Status: Recruiting
• Conditions: AKI; Surgery; CHD - Congenital Heart Disease
• Intervention / Treatment: Drug: Nitric Oxide; Drug: Oxygen

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: David S Cooepr, MD; Phone Number: 5138035448; Email: David.Cooper@cchmc.org

Study Locations

• United States
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Recruiting
      • Cincinnati Children's Hospital Medical Center
      • Contact: David S. Cooper, MD; Phone Number: 5138035448; Email: David.Cooper@cchmc.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 day to 1 month (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• All neonates (≤31 days) undergoing cardiac surgery with CPB for CHD will be deemed eligible for enrollment.

Exclusion Criteria:

1. Failure to obtain informed consent from parent/guardian
2. Clinical signs of preoperative persistent elevated pulmonary vascular resistance,
3. Emergency surgery,
4. Episode of cardiac arrest within 1 week before surgery,
5. Recent treatment with steroids and/or a condition that may require treatment with steroids (excluding steroid administration specifically for CPB),
6. Use of inhaled NO (iNO) immediately prior to surgery,
7. Structural renal abnormalities by ultrasound,
8. Preoperative AKI,
9. Use of other investigational drugs,
10. Weight less than <2 kg,
11. Gestational age <36 weeks,
12. Major extracardiac congenital anomalies,
13. Non-English speakers.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Nitric Oxide; Intraoperative NO entrained at 20 ppm into the oxygenator of the CPB circuit with standard care	Drug: Nitric Oxide; gNO will be entrained at 20 ppm into the oxygenator of the CPB circuit
Placebo Comparator: Oxygen; Standard CPB without NO administered at any point intraoperatively	Drug: Oxygen; Oxygen alone will be entrained for placebo arm

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AKI	Incidence of AKI in the first 72 hours postoperative as defined by the Kidney Disease Improving Global Outcomes (KDIGO) diagnostic classification	72 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biomarker evidence of AKI - NGAL	Incidence of structural AKI in the first 72 hours postoperative will be assessed by measurement of urine biomarker neutrophil gelatinase-associated lipocalin (NGAL)	72 hours
Biomarker evidence of AKI - KIM-1	Incidence of structural AKI in the first 72 hours postoperative will be assessed by measurement of urine biomarker kidney injury molecule-1 (KIM-1)	72 hours
Biomarker evidence of AKI - IL-18	Incidence of structural AKI in the first 72 hours postoperative will be assessed by measurement of urine biomarker interleukin-18 (IL-18)	72 hours
Biomarker evidence of AKI - L-FABP	Incidence of structural AKI in the first 72 hours postoperative will be assessed by measurement of urine biomarker liver-type fatty acid-binding protein (L-FABP)	72 hours
Biomarker evidence of AKI - urinary nitrite	Incidence of structural AKI in the first 72 hours postoperative will be assessed by measurement of urine biomarker urinary nitrate.	72 hours
Impact on GFR	Postoperative GFR measured using serum cystatin C.	72 hours
Low Cardiac Output	Incidence of low cardiac output syndrome (LCOS) during the first 48 hours postoperative	48 hours

Collaborators and Investigators

• Sponsor: Children's Hospital Medical Center, Cincinnati
• Collaborators: Indiana University; Mallinckrodt

Study record dates

Study Major Dates

• Study Start (Actual): January 10, 2023
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): June 30, 2026

Study Registration Dates

• First Submitted: December 4, 2019
• First Submitted That Met QC Criteria: December 31, 2019
• First Posted (Actual): January 3, 2020

Study Record Updates

• Last Update Posted (Actual): July 24, 2025
• Last Update Submitted That Met QC Criteria: July 21, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Congenital Abnormalities; Cardiovascular Abnormalities; Heart Diseases; Heart Defects, Congenital; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Neurotransmitter Agents; Antioxidants; Protective Agents; Respiratory System Agents; Free Radical Scavengers; Anti-Asthmatic Agents; Bronchodilator Agents; Vasodilator Agents; Endothelium-Dependent Relaxing Factors; Gasotransmitters; Nitric Oxide
• Other Study ID Numbers: MOD00004808

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes