NO During CPB in Neonates to Reduce Risk of AKI

Phase 3

Recruiting

• Conditions: AKI; CHD - Congenital Heart Disease; Surgery
• Interventions: Drug: Oxygen; Drug: Nitric Oxide

• Registration Number: NCT04216927
• Lead Sponsor: Children's Hospital Medical Center, Cincinnati

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-12-04
• Study First Submitted QC: 2019-12-31
• Study First Posted: 2020-01-03
• Study Start: 2023-01-10
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-01
• Last Update Posted: 2025-04-03
• Primary Completion: 2025-06-30
• Study Completion: 2025-06-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 40

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Oxygen	Oxygen	Standard CPB without NO administered at any point intraoperatively
Nitric Oxide	Nitric Oxide	Intraoperative NO entrained at 20 ppm into the oxygenator of the CPB circuit with standard care

Primary Outcome Measures

Name	Time	Method
AKI	72 hours	Incidence of AKI in the first 72 hours postoperative as defined by the Kidney Disease Improving Global Outcomes (KDIGO) diagnostic classification

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Cincinnati Children's Hospital Medical Center; 🇺🇸 Cincinnati, Ohio, United States