Nitric Oxide for Congenital Heart Defects

Overseen By Alistair Hilton, BA

Age: < 18

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Vanderbilt University Medical Center

Disqualifiers: Emergency surgery, Severe developmental delay, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

Duration: 1 day

50 Participants Needed

Trial Summary

What is the purpose of this trial?

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).

Will I have to stop taking my current medications?

The trial information does not specify whether participants need to stop taking their current medications.

What data supports the effectiveness of the drug Nitric Oxide (NO) for treating congenital heart defects?

Research shows that inhaled nitric oxide can help improve heart and lung function in infants after heart surgery by reducing inflammation and improving oxygen levels. It has been used to treat pulmonary hypertension (high blood pressure in the lungs) in children with congenital heart disease, showing benefits like better blood flow and reduced pressure in the lungs. ^{1 2 3 4 5}

Is inhaled nitric oxide generally safe for humans?

Inhaled nitric oxide is generally considered safe for use in humans, especially at lower doses like 10 ppm, as it is used to treat pulmonary hypertension (high blood pressure in the lungs) in patients with congenital heart disease. It has been used safely in newborns and children, and studies have shown it can improve pulmonary circulation after heart surgery. ^{1 2 3 6 7}

How does the drug nitric oxide differ from other treatments for congenital heart defects?

Nitric oxide is unique because it is inhaled and acts as a selective pulmonary vasodilator, which means it helps open up blood vessels in the lungs to improve blood flow and oxygenation. This is particularly beneficial for patients with congenital heart defects and pulmonary hypertension, as it can help manage these conditions during and after surgery. ^{1 3 4 6 8}

Research Team

David P Bichell, MD

Principal Investigator

Vanderbilt University Medical Center

Eligibility Criteria

This trial is for babies under 1 year old with congenital heart defects (CHD) who are scheduled for corrective surgery using cardiopulmonary bypass. It's not open to those needing emergency surgery, with severe developmental delays, pre-existing kidney disease, or a need for nitric oxide before surgery.

Inclusion Criteria

I am under 1 year old.

My baby is having heart surgery with a heart-lung machine.

Exclusion Criteria

I need inhaled nitric oxide right before surgery.

You have a severe developmental delay, as determined by a specific scale that measures cognitive abilities before a serious illness.

I require emergency surgery.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo cardiopulmonary bypass with or without nitric oxide administration

1 day

1 visit (in-person)

ICU Monitoring

Participants are monitored in the ICU for delirium and organ dysfunction

14 days

Daily monitoring in ICU

Follow-up

Participants are monitored for safety and effectiveness after treatment

30 days

Treatment Details

Interventions

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

Trial Overview The study tests if inhaling low doses of Nitric Oxide (NO) can protect the brain and kidneys during heart surgery. Researchers will measure specific proteins and monitor patients' recovery in the ICU to see if NO makes a difference.

Participant Groups

Group I: Nitric oxide group Experimental Treatment 1 Intervention

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

Group II: Standard of care cardiopulmonary bypass procedure Active Control 1 Intervention

Participants in this group will receive standard of care

Who Is Running the Clinical Trial?

Vanderbilt University Medical Center

Lead Sponsor

Trials

922

Recruited

939,000+

Findings from Research

Inhaled nitric oxide is an effective treatment for pulmonary hypertension in patients with congenital heart disease, particularly benefiting newborns, who made up 37% of the 400 patients treated at the center.

While it helps in diagnosing and managing conditions like total anomalous pulmonary venous connection and congenital mitral stenosis, the efficacy of inhaled nitric oxide has not been rigorously tested in randomized, placebo-controlled trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhaled nitric oxide in the neonate with cardiac disease. Atz, AM., Wessel, DL.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Study protocol: NITric oxide during cardiopulmonary bypass to improve Recovery in Infants with Congenital heart defects (NITRIC trial): a randomised controlled trial. [2020]

2. England pubmed.ncbi.nlm.nih.gov

Effect of inhaled nitric oxide on raised pulmonary vascular resistance in children with congenital heart disease. [2019]

3. United States pubmed.ncbi.nlm.nih.gov

Inhaled nitric oxide in the neonate with cardiac disease. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Effect of nitric oxide on oxygenation and hemodynamics in infants after cardiac surgery. [2019]

5. United States pubmed.ncbi.nlm.nih.gov

Very-low-dose inhaled nitric oxide: a selective pulmonary vasodilator after operations for congenital heart disease. [2017]

6. Netherlands pubmed.ncbi.nlm.nih.gov

A phase I clinical study of inhaled nitric oxide in healthy adults. [2013]

7. United States pubmed.ncbi.nlm.nih.gov

Effects of inhaled nitric oxide on postoperative pulmonary circulation in patients with congenital heart disease. [2019]

8. Australia pubmed.ncbi.nlm.nih.gov

Nitric oxide-related compounds in patients with congenital heart defects and pulmonary hypertension. [2019]