NO During CPB in Neonates to Reduce Risk of AKI
Primary Purpose
AKI, CHD - Congenital Heart Disease, Surgery
Status
Recruiting
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Nitric Oxide
Oxygen
Sponsored by
About this trial
This is an interventional prevention trial for AKI
Eligibility Criteria
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.
Sites / Locations
- Cincinnati Children's Hospital Medical CenterRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Nitric Oxide
Oxygen
Arm Description
Intraoperative NO entrained at 20 ppm into the oxygenator of the CPB circuit with standard care
Standard CPB without NO administered at any point intraoperatively
Outcomes
Primary Outcome Measures
AKI
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
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
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
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
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
Incidence of structural AKI in the first 72 hours postoperative will be assessed by measurement of urine biomarker urinary nitrate.
Impact on GFR
Postoperative GFR measured using serum cystatin C.
Low Cardiac Output
Incidence of low cardiac output syndrome (LCOS) during the first 48 hours postoperative
Full Information
NCT ID
NCT04216927
First Posted
December 4, 2019
Last Updated
March 8, 2023
Sponsor
Children's Hospital Medical Center, Cincinnati
Collaborators
Mallinckrodt, Indiana University
1. Study Identification
Unique Protocol Identification Number
NCT04216927
Brief Title
NO During CPB in Neonates to Reduce Risk of AKI
Official Title
Efficacy of Nitric Oxide Administration During Cardiopulmonary Bypass in Neonates at Reducing the Risk of Acute Kidney Injury
Study Type
Interventional
2. Study Status
Record Verification Date
March 2023
Overall Recruitment Status
Recruiting
Study Start Date
January 10, 2023 (Actual)
Primary Completion Date
December 31, 2024 (Anticipated)
Study Completion Date
June 1, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Children's Hospital Medical Center, Cincinnati
Collaborators
Mallinckrodt, Indiana University
4. Oversight
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
Data Monitoring Committee
Yes
5. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
AKI, CHD - Congenital Heart Disease, Surgery
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Sequential Assignment
Model Description
• This pilot study is a single center, double-blind, randomized controlled trial.
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
40 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Nitric Oxide
Arm Type
Experimental
Arm Description
Intraoperative NO entrained at 20 ppm into the oxygenator of the CPB circuit with standard care
Arm Title
Oxygen
Arm Type
Placebo Comparator
Arm Description
Standard CPB without NO administered at any point intraoperatively
Intervention Type
Drug
Intervention Name(s)
Nitric Oxide
Intervention Description
gNO will be entrained at 20 ppm into the oxygenator of the CPB circuit
Intervention Type
Drug
Intervention Name(s)
Oxygen
Intervention Description
Oxygen alone will be entrained for placebo arm
Primary Outcome Measure Information:
Title
AKI
Description
Incidence of AKI in the first 72 hours postoperative as defined by the Kidney Disease Improving Global Outcomes (KDIGO) diagnostic classification
Time Frame
72 hours
Secondary Outcome Measure Information:
Title
Biomarker evidence of AKI - NGAL
Description
Incidence of structural AKI in the first 72 hours postoperative will be assessed by measurement of urine biomarker neutrophil gelatinase-associated lipocalin (NGAL)
Time Frame
72 hours
Title
Biomarker evidence of AKI - KIM-1
Description
Incidence of structural AKI in the first 72 hours postoperative will be assessed by measurement of urine biomarker kidney injury molecule-1 (KIM-1)
Time Frame
72 hours
Title
Biomarker evidence of AKI - IL-18
Description
Incidence of structural AKI in the first 72 hours postoperative will be assessed by measurement of urine biomarker interleukin-18 (IL-18)
Time Frame
72 hours
Title
Biomarker evidence of AKI - L-FABP
Description
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)
Time Frame
72 hours
Title
Biomarker evidence of AKI - urinary nitrite
Description
Incidence of structural AKI in the first 72 hours postoperative will be assessed by measurement of urine biomarker urinary nitrate.
Time Frame
72 hours
Title
Impact on GFR
Description
Postoperative GFR measured using serum cystatin C.
Time Frame
72 hours
Title
Low Cardiac Output
Description
Incidence of low cardiac output syndrome (LCOS) during the first 48 hours postoperative
Time Frame
48 hours
10. Eligibility
Sex
All
Minimum Age & Unit of Time
1 Day
Maximum Age & Unit of Time
31 Days
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
David S Cooepr, MD
Phone
5138035448
Email
David.Cooper@cchmc.org
Facility Information:
Facility Name
Cincinnati Children's Hospital Medical Center
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45229
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
David S. Cooper, MD
Phone
513-803-5448
Email
David.Cooper@cchmc.org
12. IPD Sharing Statement
Plan to Share IPD
No
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NO During CPB in Neonates to Reduce Risk of AKI
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