Hypertension, Pulmonary, of Newborn, Persistent, Persistent Fetal Circulation Syndrome, Persistent Pulmonary Hypertension of Newborn
Conditions
Keywords
Persistent Fetal Circulation Syndrome, Infant, Newborn, Nitric Oxide, Oxidative Stress, Endothelin 1, Vascular Endothelial Growth Factor
Brief summary
The investigators in this study are concerned about the harmful effects of oxygen exposure in newborn infants, particularly at high concentrations. Inhaled nitric oxide (iNO) is an FDA approved drug for the treatment of hypoxic respiratory failure (HRF) in term and late-preterm babies greater than 34 weeks gestation. Hypoxic respiratory failure occurs when a patient's lungs cannot get enough oxygen into their bloodstream. This condition is traditionally treated with high concentrations of oxygen and most often requires the patient be placed on a ventilator (breathing machine). The administration of inhaled nitric oxygen directly into the lungs often improves blood oxygen levels and allows caretakers to reduce the amount of oxygen given to the baby. The purpose of this research study is to evaluate if giving the inhaled nitric oxide earlier in the course of disease improves the effectiveness of the drug, reduces the amount of cellular injury from oxygen exposure, and decreases the total amount of time a patient requires supplemental oxygen. This study uses an FDA approved drug in a new manner.
Interventions
DRUGInhaled nitric oxide
Drug is initiated at 20ppm. Patients randomized to receive iNO at OI 10-15.
DRUGNitrogen Gas
Placebo gas (bioinert), Patients randomized to bioinert inhaled gas at OI 10-15.
DRUGCrossover iNO
Patients who deteriorate (OI \>20 on two consecutive blood gases) will be unblinded. If they are receiving placebo gas, they will be started on iNO and make up the crossover cohort.
Sponsors
Mallinckrodt
University of Florida
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
30 Minutes to 48 Hours
Healthy volunteers
No
Inclusion criteria
* Gestational age ≥ 35 weeks gestation * Age of life ≤ 48 hours * Diagnosis of hypoxic respiratory failure (HRF) as defined by a post-ductal SaO2 ≤90% in ≥50% oxygen with a PEEP of ≥ 6cm or an oxygenation index (OI) ≥ 10 but ≤ 15 when mean airway pressure and PaO2 are known. * Mothers (ages 18 - 65) of eligible subjects for additional data collection
Exclusion criteria
* Gestational age \< 35 weeks gestation. * Post-natal age \> 48 hours. * Previous treatment with 100% oxygen for longer than 4 hours. * Confirmed congenital diaphragmatic hernia. * Suspected or confirmed congenital airway or pulmonary anomaly. * Suspected or confirmed chromosomal anomaly or genetic aberration, with the exception of patients with trisomy 21 who do not have complex congenital heart disease. * Infants with pneumothorax as the primary cause of their HRF. * Infants with confirmed complex congenital heart disease.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Biomarkers of oxidative injury. | Urine samples will be collected upon enrollment and then at specific time points within the first 48 hours of study intervention to compare the change in biomarker concentrations from baseline up to hour 48. | Early administration of iNO to infants with HRF will result in reduced hyperoxia-mediated oxidative injury as measured by known biomarkers of oxygen free radical injury, including malondialdehyde and 8-hydroxy-2'-deoxyguanosine. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Responsiveness to study treatment. | Arterial oxygen concentration will be measured upon enrollment and at specific time points in the first 36 hours of study intervention to compare the change in arterial oxygen concentration from baseline up to hour 36. | Earlier administration of iNO to infants with HRF/PPHN (persistent pulmonary hypertension of the newborn) will lessen reactive oxygen species formation resulting in improved responsiveness to the drug as measured by the initial changes in arterial oxygen concentration after administration of the drug. |
| Expression of endothelin-1. | Concentration of endothelin-1 will be measured upon enrollment and at specific time points in the first 36 hours of study intervention to compare the change in concentration from baseline up to hour 36. | Earlier treatment with iNO may potentiate pulmonary vasodilation by modulating endothelin-1 expression. |
| Markers of inflammation. | Concentrations of pro and anti-inflammatory markers will be measured upon enrollment and at specific time points in the first 36 hours of study intervention to compare the change in concentrations from baseline up to hour 36. | Early iNO may up-regulate production of endogenous anti-inflammatory eicosanoids such as PGE2 (prostaglandin E2). Additionally, avoidance of hyperoxia in these patients may mitigate pro-inflammatory cytokines known to potentiate lung injury. |
| Duration of oxygen treatment. | Participants will be followed for the duration of their hospital stay, with an expected average stay of 4 weeks. | Early administration of iNO to infants with HRF will result in at least a 15% reduction in total days of oxygen therapy. |
| Expression of VEGF (vascular endothelial growth factor). | Concentration of VEGF will be measured upon enrollment and at specific time points in the first 36 hours of study intervention to compare the change in concentration from baseline up to hour 36. | Earlier treatment with iNO may potentiate pulmonary vasodilation by preventing hyperoxic down regulation of VEGF. |
Countries
United States
Outcome results
None listed