Congenital Heart DiseasePhase 2/3NCT05101746
Nitric Oxide Effect on Brain and Kidney in Pediatric Patients Undergoing Cardiopulmonary Bypass
A Phase 2/3 study testing Nitric Oxide (NO) 20 part per million (ppm) in people with Congenital Heart Disease and Congenital Heart Defect, run by Vanderbilt University Medical Center at 1 site in United States.
Trial summary
The goals of this study are: 1. To evaluate the neuroprotective effect of nitric oxide by measuring glial fibrillary acid protein (GFAP) before and after surgery. GFAP will be analyzed via an enzyme-linked immunosorbent assay (ELISA) kit. Read more about this study
- Who is it for?
- Ages 0 years to 1 year
- Conditions the study is for
- Congenital Heart Disease, Congenital Heart Defect, Congenital Heart Malformations
- What is being tested?
- Nitric Oxide (NO) 20 part per million (ppm)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteUnited States
- Study dates
- 25 Apr 2022to Sep 2026
- Phase
- Phase 2/3
- 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 0 years to 1 year
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Neonates and infants with CHD undergoing CPB for corrective surgery
- Age <1 year old
Who cannot join
- Requirement of inhaled NO immediately prior to surgery
- Emergency surgery
- Severe developmental delay at baseline defined as a score of ≥ 4 (severe disability) on the Pediatric Cerebral Performance Category (PCPC) Scale, referencing cognitive status prior to critical illness
- Pre-existing renal disease
- Inability to understand English or deafness that will preclude delirium evaluation. The inability to understand English in verbal participants will not result in exclusion when the research staff is proficient and/or translation services are actively available in that particular language.
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
Vanderbilt University Medical Center
Nashville, Tennessee, 37212
About this study
Official title: Nitric Oxide Administration During Pediatric Cardiopulmonary Bypass Effects on End Organ Damage to the Brain and Kidney
The goals of this study are:
- To evaluate the neuroprotective effect of nitric oxide by measuring glial fibrillary acid protein (GFAP) before and after surgery. GFAP will be analyzed via an enzyme-linked immunosorbent assay (ELISA) kit. Patients will also be monitored post-operatively for delirium in the intensive care unit (ICU).
- To evaluate the renal protective effect of nitric oxide by measuring neutrophil gelatinase-associated lipocalin (NGAL) before and after surgery. NGAL will also be analyzed via an ELISA kit. Patient creatinine will be monitored post-operatively.
- To evaluate effect of nitric oxide on other ICU outcomes (invasive mechanical ventilation, days to extubation, ICU and hospital length of stay, and blood product administration).
Read the detailed description
Corrective cardiac surgery for congenital heart disease (CHD) requiring cardiopulmonary bypass (CPB) is associated with numerous postoperative complications including neural tissue damage resulting in long-term neurocognitive deficits as well as acute kidney injury impacting renal function. Non-cardiac organ complications result in an increased mortality and length of hospital stay. Nitric oxide (NO) has been shown to play a protective role in a systemic inflammatory response, with administration of NO reducing damage to the liver, lungs, kidney, and brain in experimental models. Recent studies have demonstrated that for pediatric CHD patients undergoing corrective surgery administration of NO to the bypass circuit resulted in myocardial protection, reduced incidence of low cardiac output syndrome, and improved post-operative ICU course. NO in adult populations undergoing CPB has also been demonstrated to decrease the incidence of acute kidney injury.
Though prior studies have shown wide ranging protective effects from NO during CPB, these have not been fully characterized for neural and renal tissue for the pediatric population. Due to NO's promise in protective effects for other end organ damage the investigators are interested in investigating its potential to mitigate damage to neural and renal tissue. The investigators hypothesize that NO administration during CPB will be associated with reduced acute neurologic insult, reduced acute kidney injury postoperatively, and increased ventilator-free days.
To test these hypotheses the investigators propose a study where one group receives the current standard of care at Vanderbilt (standard surgery and CPB) and the other group receives NO administration during CPB in addition to standard surgery and CPB. The investigators propose using validated biomarkers to determine the effect of NO on the brain and kidney. GFAP is a biomarker for acute neurologic injury and NGAL is a biomarker of acute kidney injury. The biomarkers will be analyzed from blood drawn prior to and during surgery from existing lines in place as part of the procedure and will not necessitate additional needle sticks. No devices will be evaluated in this study; the investigators will only be measuring the effect of NO on neurological, renal and other ICU outcomes.
- Being tested
- Nitric Oxide (NO) 20 part per million (ppm), Standard of care cardiopulmonary bypass
- Keywords
- pediatric heart surgery, congenital heart surgery
- 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 Oxide (NO) 20 part per million (ppm)Drug
Nitric oxide will be mixed into the gas flow of the cardiopulmonary bypass (CPB) oxygenator, which will be kept at 1-3 L/min to allow for the desired NO delivery rate. NO levels will be maintained at 20ppm using a NO delivery system (INOmax, Mallinckrodt).
Standard of care cardiopulmonary bypassOther
Cardiopulmonary bypass (CPB) will be performed using the departmental guidelines and standards. CPB will be performed using in a nonpulsatile flow with the System 1 Heart Lung Machine (Terumo Cardiovascular Systems, Ann Arbor, Mich). The maximum perfusion flow will be 200 ml/kg/minute. Blood pressure management will be selected based on the patient age and procedure. Temperature management will be to cool the patient 32 celsius (C).
| Study group | Role | What they receive |
|---|---|---|
| Nitric oxide group | Experimental | Participants in this group will receive Nitric Oxide (NO) while undergoing Cardiopulmonary bypass (CPB) Receives: Drug: Nitric Oxide (NO) 20 part per million (ppm) |
| Standard of care cardiopulmonary bypass procedure | Active comparator | Participants in this group will receive standard of care Receives: Other: Standard of care cardiopulmonary bypass |
What is being measured
The primary outcome is the main question the study is designed to answer.
Level of glial fibrillary acid protein (GFAP)
GFAP will be measured via blood sample
Measured: baseline to peak rewarming temperature of blood (approximately 3 hours)
Level of neutrophil gelatinase-associated lipocalin (NGAL)
NGAL will be measured via blood sample
Measured: baseline to 2 hours after CPB initiation (approximately 2 hours)
Secondary outcomes (7)
Daily prevalence of delirium as measured by preschool confusion assessment method for the ICU (psCAM-ICU)
Daily prevalence of delirium will be monitored using the psCAM-ICU which is currently monitored daily in the pediatric ICU. The psCAM-ICU is designed to assess for delirium in critically ill children, with or without mechanical ventilation. The psCAM-ICU was designed with cognitive testing that is developmentally appropriate for infants-5 year olds.
Patients are first assessed for arousal from -5 to +4 with -5 being unarousable to physical stimuli and +4 being combative. If arousal is greater than or equal to -3 than the patient is evaluated for the presence 4 features: 1) Acute change or fluctuating course of mental status, 2) Inattention, 3) Altered level of consciousness, 4) Disorganized thinking. Presence of 1 AND 2 AND either 3 OR 4 constitutes a positive result. The test results in the patient either being positive or negative for the presence of delirium.
Measured: date of admission to date of discharge from ICU (approximately 14 days)
Length of ICU stay
intensive care unit (ICU) length of stay measured in days
Measured: date of admission to date of discharge from ICU (approximately 14 days)
Duration of mechanical ventilation
time spent on ventilator measured in days
Measured: postoperative day 0 to hospital discharge (approximately 30 days)
Length of hospital stay
hospital length of stay measured in days
Measured: date of admission to date of hospital discharge (approximately 30 days)
Mortality
In-hospital, 90-day mortality will be tracked and recorded
Measured: date of admission to date of hospital discharge and/or 90 days post operation (approximately 90 days)
Organ dysfunction as measured by the pediatric Sequential Organ Failure Assessment
Organ dysfunctions will be tracked for up to 14 days during the Intervention Phase using the daily pediatric Sequential Organ Failure Assessment (pSOFA) scoring tool that is based on continuous as well as established predefined age appropriate cut offs for each organ failure. The following measurements are included: a. Creatinine (kidney), b. arterial oxygen saturation or arterial oxygen partial pressure over the fraction of inspired oxygen (lung), c. Total bilirubin (hepatic), d. Platelet count (coagulation), e. Glasgow coma score (neurologic), and f. Hemodynamic indices with +/-need for vasopressor (cardiovascular). These each receive a score of 0 to 4 based on the severity of the lab findings abnormality, with 0 being normal and 4 being the most severe. These are used to calculate a total score of 0 to 24, with 24 indicating a high risk of poor outcomes.
Measured: date of admission up to 14 days
Functional Status
Functional Status Scale (FSS) will be measured at admission for baseline and again at hospital discharge. The FSS is a survey that tracks 6 domains (mental status, sensory, communication, motor function, feeding, respiratory) with a scoring from 1 to 5 each, with 1 being normal function and 5 being very severe dysfunction. Total scores will range from 6 to 30, with 6 being normal function and 30 being very severe dysfunction.
Measured: date of admission to date of hospital discharge (approximately 30 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Nov 2021
- Study start25 Apr 2022
- Primary completionSep 2026 (estimated)
- Study completionSep 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Congenital Heart DiseaseStudies of the same condition, open and under way.
- More trials run by Vanderbilt University Medical CenterThe 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Vanderbilt University Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, David Bichell, Vanderbilt University Medical Center
- Investigators
- David P Bichell, MD, Principal investigator, Vanderbilt University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05101746
- Sponsor's protocol ID
- 211416
- Status last verified
- Sep 2025
- First submitted
- 17 Sep 2021
- Last updated
- 8 Oct 2025
- Results posted
- No
- Data monitoring committee
- No
- 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 8 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Nitric Oxide Administration During Pediatric Cardiopulmonary Bypass Effects on End Organ Damage to the Brain and Kidney
- ClinicalTrials.gov ID
- NCT05101746
- Acronym / sponsor ID
- 211416
- Keywords
- pediatric heart surgery, congenital heart surgery
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Enrolling by invitation
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Vanderbilt University Medical CenterUniversity, hospital or other
- Study start
- 25 Apr 2022 (actual)
- Primary completion
- Sep 2026 (estimated)
- Study completion
- Sep 2026 (estimated)
- First posted
- 1 Nov 2021 (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.
The goals of this study are:
- To evaluate the neuroprotective effect of nitric oxide by measuring glial fibrillary acid protein (GFAP) before and after surgery. GFAP will be analyzed via an enzyme-linked immunosorbent assay (ELISA) kit. Patients will also be monitored post-operatively for delirium in the intensive care unit (ICU).
- To evaluate the renal protective effect of nitric oxide by measuring neutrophil gelatinase-associated lipocalin (NGAL) before and after surgery. NGAL will also be analyzed via an ELISA kit. Patient creatinine will be monitored post-operatively.
- To evaluate effect of nitric oxide on other ICU outcomes (invasive mechanical ventilation, days to extubation, ICU and hospital length of stay, and blood product administration).
Detailed description
Corrective cardiac surgery for congenital heart disease (CHD) requiring cardiopulmonary bypass (CPB) is associated with numerous postoperative complications including neural tissue damage resulting in long-term neurocognitive deficits as well as acute kidney injury impacting renal function. Non-cardiac organ complications result in an increased mortality and length of hospital stay. Nitric oxide (NO) has been shown to play a protective role in a systemic inflammatory response, with administration of NO reducing damage to the liver, lungs, kidney, and brain in experimental models. Recent studies have demonstrated that for pediatric CHD patients undergoing corrective surgery administration of NO to the bypass circuit resulted in myocardial protection, reduced incidence of low cardiac output syndrome, and improved post-operative ICU course. NO in adult populations undergoing CPB has also been demonstrated to decrease the incidence of acute kidney injury.
Though prior studies have shown wide ranging protective effects from NO during CPB, these have not been fully characterized for neural and renal tissue for the pediatric population. Due to NO's promise in protective effects for other end organ damage the investigators are interested in investigating its potential to mitigate damage to neural and renal tissue. The investigators hypothesize that NO administration during CPB will be associated with reduced acute neurologic insult, reduced acute kidney injury postoperatively, and increased ventilator-free days.
To test these hypotheses the investigators propose a study where one group receives the current standard of care at Vanderbilt (standard surgery and CPB) and the other group receives NO administration during CPB in addition to standard surgery and CPB. The investigators propose using validated biomarkers to determine the effect of NO on the brain and kidney. GFAP is a biomarker for acute neurologic injury and NGAL is a biomarker of acute kidney injury. The biomarkers will be analyzed from blood drawn prior to and during surgery from existing lines in place as part of the procedure and will not necessitate additional needle sticks. No devices will be evaluated in this study; the investigators will only be measuring the effect of NO on neurological, renal and other ICU outcomes.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Nitric oxide group | Experimental | Drug: Nitric Oxide (NO) 20 part per million (ppm)Participants in this group will receive Nitric Oxide (NO) while undergoing Cardiopulmonary bypass (CPB) |
| Standard of care cardiopulmonary bypass procedure | Active comparator | Other: Standard of care cardiopulmonary bypassParticipants in this group will receive standard of care |
Who may qualify
- Ages
- 0 years to 1 year
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (2 listed)
- Neonates and infants with CHD undergoing CPB for corrective surgery
- Age <1 year old
Key exclusion criteria (5 listed)
- Requirement of inhaled NO immediately prior to surgery
- Emergency surgery
- Severe developmental delay at baseline defined as a score of ≥ 4 (severe disability) on the Pediatric Cerebral Performance Category (PCPC) Scale, referencing cognitive status prior to critical illness
- Pre-existing renal disease
- Inability to understand English or deafness that will preclude delirium evaluation. The inability to understand English in verbal participants will not result in exclusion when the research staff is proficient and/or translation services are actively available in that particular language.
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 Oxide (NO) 20 part per million (ppm)Nitric oxide will be mixed into the gas flow of the cardiopulmonary bypass (CPB) oxygenator, which will be kept at 1-3 L/min to allow for the desired NO delivery rate. NO levels will be maintained at 20ppm using a NO delivery system (INOmax, Mallinckrodt). | Drug | Nitric oxide group |
| Standard of care cardiopulmonary bypassCardiopulmonary bypass (CPB) will be performed using the departmental guidelines and standards. CPB will be performed using in a nonpulsatile flow with the System 1 Heart Lung Machine (Terumo Cardiovascular Systems, Ann Arbor, Mich). The maximum perfusion flow will be 200 ml/kg/minute. Blood pressure management will be selected based on the patient age and procedure. Temperature management will be to cool the patient 32 celsius (C). | Other | Standard of care cardiopulmonary bypass procedure |
Primary outcome
Level of glial fibrillary acid protein (GFAP)
Time frame: baseline to peak rewarming temperature of blood (approximately 3 hours)
GFAP will be measured via blood sample
Level of neutrophil gelatinase-associated lipocalin (NGAL)
Time frame: baseline to 2 hours after CPB initiation (approximately 2 hours)
NGAL will be measured via blood sample
7 secondary outcomes
Daily prevalence of delirium as measured by preschool confusion assessment method for the ICU (psCAM-ICU)
Time frame: date of admission to date of discharge from ICU (approximately 14 days)
Length of ICU stay
Time frame: date of admission to date of discharge from ICU (approximately 14 days)
Duration of mechanical ventilation
Time frame: postoperative day 0 to hospital discharge (approximately 30 days)
Length of hospital stay
Time frame: date of admission to date of hospital discharge (approximately 30 days)
Mortality
Time frame: date of admission to date of hospital discharge and/or 90 days post operation (approximately 90 days)
Organ dysfunction as measured by the pediatric Sequential Organ Failure Assessment
Time frame: date of admission up to 14 days
Functional Status
Time frame: date of admission to date of hospital discharge (approximately 30 days)
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 8 Oct 2025.
- 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.
David P Bichell, MD principal investigator
Vanderbilt University Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Nitric Oxide (NO) 20 part per million (ppm) in people with Congenital Heart Disease and Congenital Heart Defect, run by Vanderbilt University Medical Center 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 2 inclusion and 5 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: enrolling by invitation, as of the sponsor's last update on 8 Oct 2025. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Level of glial fibrillary acid protein (GFAP) (time frame: baseline to peak rewarming temperature of blood (approximately 3 hours)). The study lists 2 primary outcomes in all. 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 8 Oct 2025.