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

NCT01891500 | Withdrawn Phase 4 DMC FDA Drug

• 3 other identifiers: IRB20140079100089105OCR17867
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Persistent Fetal Circulation Syndrome; Hypertension, Pulmonary, of Newborn, Persistent; Persistent Pulmonary Hypertension of Newborn

Keywords

Persistent Fetal Circulation Syndrome; Infant, Newborn; Nitric Oxide; Oxidative Stress; Endothelin 1; Vascular Endothelial Growth Factor

Outcome Measures

Primary Outcomes (1)

• Biomarkers of oxidative injury.

  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.

  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.

Secondary Outcomes (5)

• 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.

• 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.

• 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.

• Duration of oxygen treatment.

  Participants will be followed for the duration of their hospital stay, with an expected average stay of 4 weeks.

• 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.

Study Arms (3)

Early inhaled nitric oxide

EXPERIMENTAL

Patients randomized to receive iNO at OI 10-15.

Drug: Inhaled nitric oxide

Bioinert inhaled gas (nitrogen gas)

PLACEBO COMPARATOR

Patients randomized to bioinert inhaled gas at OI 10-15.

Drug: Nitrogen Gas

Crossover iNO

ACTIVE COMPARATOR

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.

Drug: Crossover iNO

Interventions

Inhaled nitric oxide DRUG

Drug is initiated at 20ppm. Patients randomized to receive iNO at OI 10-15.

Also known as: INOmax

Early inhaled nitric oxide

Nitrogen Gas DRUG

Placebo gas (bioinert), Patients randomized to bioinert inhaled gas at OI 10-15.

Also known as: bioinert

Bioinert inhaled gas (nitrogen gas)

Crossover iNO DRUG

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.

Also known as: bioinert, INOmax

Crossover iNO

Eligibility Criteria

• Age: 30 Minutes - 48 Hours
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Florida: lead
• Mallinckrodt: collaborator

Study Sites (1)

Shands Hospital at the University of Florida

Gainesville, Florida, 32610, United States

Location

MeSH Terms

Conditions

Persistent Fetal Circulation Syndrome

Interventions

Endothelium-Dependent Relaxing Factors; Nitrogen

Condition Hierarchy (Ancestors)

Hypertension, Pulmonary; Lung Diseases; Respiratory Tract Diseases; Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Vasodilator Agents; Cardiovascular Agents; Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses; Elements; Inorganic Chemicals; Gases

Study Officials

• Catalina Bazacliu, MD

  University of Florida

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 19, 2013
• First Posted: July 3, 2013
• Study Start: May 1, 2016
• Primary Completion: September 18, 2019
• Study Completion: September 19, 2019
• Last Updated: January 7, 2020

Record last verified: 2020-01

Locations

US (1)