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

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified March 2014 by University of Florida
Sponsor:
Collaborator:
Ikaria
Information provided by (Responsible Party):
University of Florida
ClinicalTrials.gov Identifier:
NCT01891500
First received: June 19, 2013
Last updated: March 3, 2014
Last verified: March 2014
  Purpose

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.


Condition Intervention Phase
Persistent Fetal Circulation Syndrome
Hypertension, Pulmonary, of Newborn, Persistent
Persistent Pulmonary Hypertension of Newborn
Drug: Inhaled nitric oxide
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Effect of Early iNO on Oxidative Stress, Vascular Tone and Inflammation in Term and Late-Preterm Infants With Hypoxic Respiratory Failure

Resource links provided by NLM:


Further study details as provided by University of Florida:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Estimated Enrollment: 24
Study Start Date: July 2014
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: July 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Early inhaled nitric oxide
Patients randomized to receive iNO at OI 10-15.
Drug: Inhaled nitric oxide
Drug is initiated at 20ppm.
Other Name: INOmax
Placebo Comparator: Bioinert inhaled gas
Patients randomized to bioinert inhaled gas at OI 10-15.
Active Comparator: Crossover iNO
Patients who deteriorate on placebo gas and crossover to iNO at OI >20 on two consecutive blood gases.
Drug: Inhaled nitric oxide
Drug is initiated at 20ppm.
Other Name: INOmax

  Eligibility

Ages Eligible for Study:   up to 48 Hours
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01891500

Contacts
Contact: Julie S Baines, MD 352-273-8985 bainesj@peds.ufl.edu
Contact: Cindy K Miller, RN 352-273-8985 millek@peds.ufl.edu

Locations
United States, Florida
Shands Hospital at the University of Florida Not yet recruiting
Gainesville, Florida, United States, 32610
Contact: Julie S Baines, MD    352-273-8985    bainesj@peds.ufl.edu   
Principal Investigator: Julie S Baines, MD         
Sub-Investigator: Michael D Weiss, MD         
Sponsors and Collaborators
University of Florida
Ikaria
Investigators
Principal Investigator: Julie S Baines, MD University of Florida
  More Information

No publications provided

Responsible Party: University of Florida
ClinicalTrials.gov Identifier: NCT01891500     History of Changes
Other Study ID Numbers: 00089105
Study First Received: June 19, 2013
Last Updated: March 3, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Florida:
Persistent Fetal Circulation Syndrome
Infant, Newborn
Nitric Oxide
Oxidative Stress
Endothelin 1
Vascular Endothelial Growth Factor

Additional relevant MeSH terms:
Infant, Newborn, Diseases
Hypertension
Hypertension, Pulmonary
Inflammation
Persistent Fetal Circulation Syndrome
Respiratory Insufficiency
Syndrome
Cardiovascular Diseases
Disease
Lung Diseases
Pathologic Processes
Respiration Disorders
Respiratory Tract Diseases
Vascular Diseases
Nitric Oxide
Anti-Asthmatic Agents
Antioxidants
Autonomic Agents
Bronchodilator Agents
Cardiovascular Agents
Endothelium-Dependent Relaxing Factors
Free Radical Scavengers
Gasotransmitters
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Protective Agents
Respiratory System Agents

ClinicalTrials.gov processed this record on November 24, 2014