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

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2016 by University of Florida
Sponsor:
Collaborator:
Mallinckrodt
Information provided by (Responsible Party):
University of Florida
ClinicalTrials.gov Identifier:
NCT01891500
First received: June 19, 2013
Last updated: September 6, 2016
Last verified: September 2016
History of Changes

June 19, 2013
September 6, 2016
May 2016
November 2017   (final data collection date for primary outcome measure)
Biomarkers of oxidative injury. [ Time Frame: 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. ] [ Designated as safety issue: No ]
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.
Same as current
Complete list of historical versions of study NCT01891500 on ClinicalTrials.gov Archive Site
  • Responsiveness to study treatment. [ Time Frame: 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. ] [ Designated as safety issue: No ]
    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. [ Time Frame: 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. ] [ Designated as safety issue: No ]
    Earlier treatment with iNO may potentiate pulmonary vasodilation by modulating endothelin-1 expression.
  • Markers of inflammation. [ Time Frame: 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. ] [ Designated as safety issue: No ]
    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. [ Time Frame: Participants will be followed for the duration of their hospital stay, with an expected average stay of 4 weeks. ] [ Designated as safety issue: No ]
    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). [ Time Frame: 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. ] [ Designated as safety issue: No ]
    Earlier treatment with iNO may potentiate pulmonary vasodilation by preventing hyperoxic down regulation of VEGF.
  • Responsiveness to study treatment. [ Time Frame: 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. ] [ Designated as safety issue: No ]
    Earlier administration of iNO to infants with HRF/PPHN 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. [ Time Frame: 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. ] [ Designated as safety issue: No ]
    Earlier treatment with iNO may potentiate pulmonary vasodilation by modulating endothelin-1 expression.
  • Markers of inflammation. [ Time Frame: 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. ] [ Designated as safety issue: No ]
    Early iNO may up-regulate production of endogenous anti-inflammatory eicosanoids such as PGE2. Additionally, avoidance of hyperoxia in these patients may mitigate pro-inflammatory cytokines known to potentiate lung injury.
  • Duration of oxygen treatment. [ Time Frame: Participants will be followed for the duration of their hospital stay, with an expected average stay of 4 weeks. ] [ Designated as safety issue: No ]
    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). [ Time Frame: 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. ] [ Designated as safety issue: No ]
    Earlier treatment with iNO may potentiate pulmonary vasodilation by preventing hyperoxic down regulation of VEGF.
Not Provided
Not Provided
 
Early iNO for Oxidative Stress, Vascular Tone and Inflammation in Babies With Hypoxic Respiratory Failure
Effect of Early iNO on Oxidative Stress, Vascular Tone and Inflammation in Term and Late-Preterm Infants With Hypoxic Respiratory Failure
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.
Not Provided
Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
  • Persistent Fetal Circulation Syndrome
  • Hypertension, Pulmonary, of Newborn, Persistent
  • Persistent Pulmonary Hypertension of Newborn
  • Drug: Inhaled nitric oxide
    Drug is initiated at 20ppm. Patients randomized to receive iNO at OI 10-15.
    Other Name: INOmax
  • Drug: Nitrogen Gas
    Placebo gas (bioinert), Patients randomized to bioinert inhaled gas at OI 10-15.
    Other Name: bioinert
  • Drug: 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.
    Other Names:
    • bioinert
    • INOmax
  • Experimental: Early inhaled nitric oxide
    Patients randomized to receive iNO at OI 10-15.
    Intervention: Drug: Inhaled nitric oxide
  • Placebo Comparator: Bioinert inhaled gas (nitrogen gas)
    Patients randomized to bioinert inhaled gas at OI 10-15.
    Intervention: Drug: Nitrogen Gas
  • Active Comparator: 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.
    Intervention: Drug: Crossover iNO
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
24
December 2017
November 2017   (final data collection date for primary outcome measure)

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.

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.
Both
up to 48 Hours   (Child)
No
Contact: Catalina Bazacliu, MD 352-273-8985 cbazacliu@peds.ufl.edu
Contact: Kelly D Curry, MSN 352 273 8979 hernack1@ufl.edu
United States
 
NCT01891500
IRB201400791, 00089105
Yes
Not Provided
Not Provided
University of Florida
University of Florida
Mallinckrodt
Principal Investigator: Catalina Bazacliu, MD University of Florida
University of Florida
September 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP