NO During CPB in Neonates to Reduce Risk of AKI

NCT04216927 | Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: MOD00004808
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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.

Conditions

AKI; CHD - Congenital Heart Disease; Surgery

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• Biomarker evidence of AKI - NGAL

  72 hours

• Biomarker evidence of AKI - KIM-1

  72 hours

• Biomarker evidence of AKI - IL-18

  72 hours

• Biomarker evidence of AKI - L-FABP

  72 hours

• Biomarker evidence of AKI - urinary nitrite

  72 hours

Study Arms (2)

Nitric Oxide

EXPERIMENTAL

Intraoperative NO entrained at 20 ppm into the oxygenator of the CPB circuit with standard care

Drug: Nitric Oxide

Oxygen

PLACEBO COMPARATOR

Standard CPB without NO administered at any point intraoperatively

Drug: Oxygen

Interventions

Nitric Oxide DRUG

gNO will be entrained at 20 ppm into the oxygenator of the CPB circuit

Nitric Oxide

Oxygen DRUG

Oxygen alone will be entrained for placebo arm

Oxygen

Eligibility Criteria

• Age: 1 Day - 31 Days
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• Children's Hospital Medical Center, Cincinnati: lead
• Mallinckrodt: collaborator
• Indiana University: collaborator

Study Sites (1)

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

RECRUITING

MeSH Terms

Conditions

Heart Defects, Congenital

Interventions

Nitric Oxide; Oxygen

Condition Hierarchy (Ancestors)

Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Reactive Nitrogen Species; Free Radicals; Inorganic Chemicals; Nitrogen Oxides; Nitrogen Compounds; Oxides; Oxygen Compounds; Organic Chemicals; Chalcogens; Elements; Gases

Central Study Contacts

David S Cooepr, MD

CONTACT

5138035448; David.Cooper@cchmc.org

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: • This pilot study is a single center, double-blind, randomized controlled trial.

Study Record Dates

• First Submitted: December 4, 2019
• First Posted: January 3, 2020
• Study Start: January 10, 2023
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): June 30, 2026
• Last Updated: July 24, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)