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 February 2017 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: February 2, 2017

Last verified: February 2017

History of Changes

Tracking Information

First Received Date ^ICMJE

June 19, 2013

Last Updated Date

February 2, 2017

Actual Start Date ^ICMJE

May 2016

Estimated Primary Completion Date

November 2017 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures ^ICMJE

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. ]

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.

Original Primary Outcome Measures ^ICMJE

Same as current

Change History

Complete list of historical versions of study NCT01891500 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures ^ICMJE

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. ]
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. ]
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. ]
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. ]
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. ]
Earlier treatment with iNO may potentiate pulmonary vasodilation by preventing hyperoxic down regulation of VEGF.

Original Secondary Outcome Measures ^ICMJE

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. ]
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. ]
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. ]
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. ]
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. ]
Earlier treatment with iNO may potentiate pulmonary vasodilation by preventing hyperoxic down regulation of VEGF.

Current Other Outcome Measures ^ICMJE

Not Provided

Original Other Outcome Measures ^ICMJE

Not Provided

Descriptive Information

Brief Title ^ICMJE

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

Official Title ^ICMJE

Effect of Early iNO on Oxidative Stress, Vascular Tone and Inflammation in Term and Late-Preterm Infants With Hypoxic Respiratory Failure

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 Provided

Study Type ^ICMJE

Interventional

Study Phase

Phase 4

Study Design ^ICMJE

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Participant, Care Provider, Investigator
Primary Purpose: Treatment

Condition ^ICMJE

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

Intervention ^ICMJE

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

Study Arms

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

Publications *

Not Provided

* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.

Recruitment Information

Recruitment Status ^ICMJE

Recruiting

Estimated Enrollment ^ICMJE

Estimated Completion Date

December 2017

Estimated Primary Completion Date

November 2017 (Final data collection date for primary outcome measure)

Eligibility Criteria ^ICMJE

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.

Sex/Gender

Sexes Eligible for Study:

All

Ages

up to 48 Hours (Child)

Accepts Healthy Volunteers

Contacts ^ICMJE

Contact: Catalina Bazacliu, MD	352-273-8985	cbazacliu@peds.ufl.edu
Contact: Kelly D Curry, MSN	352 273 8979	hernack1@ufl.edu

Listed Location Countries ^ICMJE

United States

Removed Location Countries

Administrative Information

NCT Number ^ICMJE

NCT01891500

Other Study ID Numbers ^ICMJE

IRB201400791
00089105 ( Other Identifier: RAC )

Has Data Monitoring Committee

Yes

U.S. FDA-regulated Product

Studies a U.S. FDA-regulated Drug Product:	Yes
Studies a U.S. FDA-regulated Device Product:	No

Plan to Share Data

Not Provided

IPD Description

Not Provided

Responsible Party

University of Florida

Study Sponsor ^ICMJE

University of Florida

Collaborators ^ICMJE

Mallinckrodt

Investigators ^ICMJE

Principal Investigator:

Catalina Bazacliu, MD

University of Florida

Information Provided By

University of Florida

Verification Date

February 2017

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

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