Nitric Oxide Effect on Brain and Kidney in Pediatric Patients Undergoing Cardiopulmonary Bypass

NCT ID: NCT05101746

Last Updated: 2025-10-08

Basic Information

• Recruitment Status: ENROLLING_BY_INVITATION
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-04-25
• Study Completion Date: 2026-09-30

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.

Conditions

Congenital Heart Disease; Congenital Heart Defect; Congenital Heart Malformations

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Nitric oxide group

Participants in this group will receive Nitric Oxide (NO) while undergoing Cardiopulmonary bypass (CPB)

Group Type: EXPERIMENTAL

Nitric Oxide (NO) 20 part per million (ppm)

Intervention Type: 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 bypass procedure

Participants in this group will receive standard of care

Group Type: ACTIVE_COMPARATOR

Standard of care cardiopulmonary bypass

Intervention Type: OTHER

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).

Interventions

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).

Intervention Type: DRUG

Standard of care cardiopulmonary bypass

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).

Intervention Type: OTHER

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.

• Minimum Eligible Age: 0 Years
• Maximum Eligible Age: 1 Year
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Vanderbilt University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

David Bichell

Chief, Pediatric Cardiac Surgery

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

David P Bichell, MD

Role: PRINCIPAL_INVESTIGATOR

Vanderbilt University Medical Center

Locations

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Countries

United States

Other Identifiers

211416

Identifier Type: -

Identifier Source: org_study_id