NO During CPB in Neonates to Reduce Risk of AKI

Sponsor

Children's Hospital Medical Center, Cincinnati (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT04216927

Collaborator

Mallinckrodt (Industry), Indiana University (Other)

Enrollment

Location

Arms

Anticipated Duration (Months)

1.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
AKI CHD - Congenital Heart Disease Surgery	Drug: Nitric Oxide Drug: Oxygen	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

40 participants

Allocation:

Randomized

Intervention Model:

Sequential Assignment

Intervention Model Description:

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

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Prevention

Official Title:

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

Anticipated Study Start Date :

Sep 30, 2022

Anticipated Primary Completion Date :

Dec 31, 2024

Anticipated Study Completion Date :

Jun 1, 2025

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

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

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 - 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 - 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 - 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 - 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

Eligibility Criteria

Criteria

Ages Eligible for Study:

1 Day to 31 Days

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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

Exclusion Criteria:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio	United States	45229

Sponsors and Collaborators

Children's Hospital Medical Center, Cincinnati
Mallinckrodt
Indiana University

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Children's Hospital Medical Center, Cincinnati

ClinicalTrials.gov Identifier:

NCT04216927

Other Study ID Numbers:

MOD00004808

First Posted:

Jan 3, 2020

Last Update Posted:

Aug 24, 2022

Last Verified:

Aug 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Product Manufactured in and Exported from the U.S.:

Yes

Additional relevant MeSH terms:

Heart Diseases

Heart Defects, Congenital

Nitric Oxide

Study Results

No Results Posted as of Aug 24, 2022