Early iNO for Oxidative Stress, Vascular Tone and Inflammation in Babies With Hypoxic Respiratory Failure

Phase 4

Withdrawn

• Conditions: Hypertension, Pulmonary, of Newborn, Persistent; Persistent Fetal Circulation Syndrome; Persistent Pulmonary Hypertension of Newborn
• Interventions: Drug: Crossover iNO; Drug: Nitrogen Gas; Drug: Inhaled nitric oxide

• Registration Number: NCT01891500
• Lead Sponsor: University of Florida

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.

Detailed Description

Not available

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2013-06-19
• Study First Submitted QC: 2013-06-28
• Study First Posted: 2013-07-03
• Study Start: 2016-05
• Primary Completion: 2019-09-18
• Study Completion: 2019-09-19
• Status Verified: 2020-01
• Last Update Submitted: 2020-01-05
• Last Update Posted: 2020-01-07

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Crossover iNO	Crossover 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.
Bioinert inhaled gas (nitrogen gas)	Nitrogen Gas	Patients randomized to bioinert inhaled gas at OI 10-15.
Early inhaled nitric oxide	Inhaled nitric oxide	Patients randomized to receive iNO at OI 10-15.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.
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 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.
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.

Trial Locations

Locations (1)

Shands Hospital at the University of Florida; 🇺🇸 Gainesville, Florida, United States