Clinical trial NCT05101746: Nitric Oxide Effect on Brain and Kidney in Pediatric Patients Undergoing Cardiopulmonary Bypass
Official title: Nitric Oxide Administration During Pediatric Cardiopulmonary Bypass Effects on End Organ Damage to the Brain and Kidney
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: PHASE2
PHASE3
Conditions: Congenital Heart Disease
Congenital Heart Defect
Congenital Heart Malformations
Keywords: pediatric heart surgery
congenital heart surgery
Lead sponsor: Vanderbilt University Medical Center
Sponsor class: OTHER
First posted: 2021-11-01
Enrollment: 50
Sex: ALL
Minimum age (years): 0
Maximum age (years): 1
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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. Patients will also be monitored post-operatively for delirium in the intensive care unit (ICU).
2. 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.
3. 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.

Eligibility criteria: Inclusion Criteria:

1. Neonates and infants with CHD undergoing CPB for corrective surgery
2. Age \<1 year old

Exclusion Criteria:

1. Requirement of inhaled NO immediately prior to surgery
2. Emergency surgery
3. 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
4. Pre-existing renal disease
5. 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.

Primary outcomes:
measure: Level of glial fibrillary acid protein (GFAP)
timeFrame: baseline to peak rewarming temperature of blood (approximately 3 hours)
measure: Level of neutrophil gelatinase-associated lipocalin (NGAL)
timeFrame: baseline to 2 hours after CPB initiation (approximately 2 hours)
Secondary outcomes:
measure: Daily prevalence of delirium as measured by preschool confusion assessment method for the ICU (psCAM-ICU)
timeFrame: date of admission to date of discharge from ICU (approximately 14 days)
measure: Length of ICU stay
timeFrame: date of admission to date of discharge from ICU (approximately 14 days)
measure: Duration of mechanical ventilation
timeFrame: postoperative day 0 to hospital discharge (approximately 30 days)
measure: Length of hospital stay
timeFrame: date of admission to date of hospital discharge (approximately 30 days)
measure: Mortality
timeFrame: date of admission to date of hospital discharge and/or 90 days post operation (approximately 90 days)
measure: Organ dysfunction as measured by the pediatric Sequential Organ Failure Assessment
timeFrame: date of admission up to 14 days
measure: Functional Status
timeFrame: date of admission to date of hospital discharge (approximately 30 days)
Other outcomes:
Locations:
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
Study officials:
affiliation: Vanderbilt University Medical Center
name: David P Bichell, MD
role: PRINCIPAL_INVESTIGATOR
References: