AKIPhase 3NCT04216927
NO During CPB in Neonates to Reduce Risk of AKI
A Phase 3 study testing Nitric Oxide and Oxygen in people with AKI and CHD - Congenital Heart Disease, run by Children's Hospital Medical Center, Cincinnati at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 1 day to 31 days
- Conditions the study is for
- AKI, CHD - Congenital Heart Disease, Surgery
- What is being tested?
- Nitric Oxide and Oxygen
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 40 participants
- Where
- 1 siteUnited States
- Study dates
- 10 Jan 2023to 30 Jun 2027
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 day to 31 days
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- All neonates (≤31 days) undergoing cardiac surgery with CPB for CHD will be deemed eligible for enrollment.
Who cannot join
- 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,
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- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
David S. Cooper, MD, 5138035448, David.Cooper@cchmc.org
About this study
Official title: 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.
- Conditions
- AKI, CHD - Congenital Heart Disease, Surgery
- Being tested
- Nitric Oxide, Oxygen
- Medical subject headings
- Heart Defects, Congenital
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nitric OxideDrug
gNO will be entrained at 20 ppm into the oxygenator of the CPB circuit
OxygenDrug
Oxygen alone will be entrained for placebo arm
| Study group | Role | What they receive |
|---|---|---|
| Nitric Oxide | Experimental | Intraoperative NO entrained at 20 ppm into the oxygenator of the CPB circuit with standard care Receives: Drug: Nitric Oxide |
| Oxygen | Placebo comparator | Standard CPB without NO administered at any point intraoperatively Receives: Drug: Oxygen |
What is being measured
The primary outcome is the main question the study is designed to answer.
AKI
Incidence of AKI in the first 72 hours postoperative as defined by the Kidney Disease Improving Global Outcomes (KDIGO) diagnostic classification
Measured: 72 hours
Secondary outcomes (7)
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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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.
Measured: 72 hours
Impact on GFR
Postoperative GFR measured using serum cystatin C.
Measured: 72 hours
Low Cardiac Output
Incidence of low cardiac output syndrome (LCOS) during the first 48 hours postoperative
Measured: 48 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Jan 2020
- Study start10 Jan 2023
- Primary completion30 Jun 2027 (estimated)
- Study completion30 Jun 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for AKIStudies of the same condition, open and under way.
- More trials run by Children's Hospital Medical Center, CincinnatiThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Sequential
- Model description
- • This pilot study is a single center, double-blind, randomized controlled trial.
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Children's Hospital Medical Center, Cincinnati
- Sponsor type
- University, hospital or other
- Collaborators
- Mallinckrodt, Indiana University
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04216927
- Sponsor's protocol ID
- MOD00004808
- Status last verified
- Aug 2026
- First submitted
- 4 Dec 2019
- Last updated
- 5 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy of Nitric Oxide Administration During Cardiopulmonary Bypass in Neonates at Reducing the Risk of Acute Kidney Injury
- ClinicalTrials.gov ID
- NCT04216927
- Acronym / sponsor ID
- MOD00004808
- Conditions
- AKI, CHD - Congenital Heart Disease, Surgery
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Children's Hospital Medical Center, CincinnatiUniversity, hospital or other
- Collaborators
- Mallinckrodt, Indiana University
- Study start
- 10 Jan 2023 (actual)
- Primary completion
- 30 Jun 2027 (estimated)
- Study completion
- 30 Jun 2027 (estimated)
- First posted
- 3 Jan 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
- Model description
- • This pilot study is a single center, double-blind, randomized controlled trial.
| Arm | Type | Receives |
|---|---|---|
| Nitric Oxide | Experimental | Drug: Nitric OxideIntraoperative NO entrained at 20 ppm into the oxygenator of the CPB circuit with standard care |
| Oxygen | Placebo comparator | Drug: OxygenStandard CPB without NO administered at any point intraoperatively |
Who may qualify
- Ages
- 1 day to 31 days
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (1 listed)
- All neonates (≤31 days) undergoing cardiac surgery with CPB for CHD will be deemed eligible for enrollment.
Key exclusion criteria (13 listed)
- 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),
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Nitric OxidegNO will be entrained at 20 ppm into the oxygenator of the CPB circuit | Drug | Nitric Oxide |
| OxygenOxygen alone will be entrained for placebo arm | Drug | Oxygen |
Primary outcome
AKI
Time frame: 72 hours
Incidence of AKI in the first 72 hours postoperative as defined by the Kidney Disease Improving Global Outcomes (KDIGO) diagnostic classification
7 secondary outcomes
Biomarker evidence of AKI - NGAL
Time frame: 72 hours
Biomarker evidence of AKI - KIM-1
Time frame: 72 hours
Biomarker evidence of AKI - IL-18
Time frame: 72 hours
Biomarker evidence of AKI - L-FABP
Time frame: 72 hours
Biomarker evidence of AKI - urinary nitrite
Time frame: 72 hours
Impact on GFR
Time frame: 72 hours
Low Cardiac Output
Time frame: 48 hours
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Aug 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Nitric Oxide and Oxygen in people with AKI and CHD - Congenital Heart Disease, run by Children's Hospital Medical Center, Cincinnati at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 5 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact David S Cooepr, MD (5138035448, David.Cooper@cchmc.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
AKI (time frame: 72 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Aug 2026.