Inhaled Nitric Oxide (iNO) as an Adjunct to Neonatal Resuscitation (iNO)

Administration of Inhaled Nitric Oxide (iNO) as an Adjunct to Neonatal Resuscitation Protocol: A Pilot Trial

This study hopes to determine whether nitric oxide along with oxygen during the first 20 minutes of life in infants needing help with breathing will reduce the percentage and total exposure to oxygen during that time frame. Although the use of oxygen in management of breathing is an important part of supporting baby immediately after delivery, there is more evidence that too much exposure to oxygen may lead to potential problems for your baby later. Oxygen exposure can be harmful to premature babies developing lungs.

Study Overview

• Status: Completed
• Conditions: Very Low Birth Weight Baby; Respiratory Distress Syndrome in Premature Infants
• Intervention / Treatment: Other: Nitrogen; Drug: iNO

Detailed Description

Current Neonatal Resuscitation Program (NRP) guidelines suggest the use of supplemental oxygen up to fraction of inspired oxygen of 1.0 during neonatal resuscitation for both term and preterm newborns. Exposure to supplemental oxygen in preterm babies has been shown to have significant toxicity. Even minimal exposure in the first hours of life has been shown to be associated with morbidity including later onset of cancer. The transition from fetal circulation to neonatal circulation is a complex process requiring lung inflation and decrease in pulmonary vascular resistance. Endogenous nitric oxide, along with oxygen, plays a major role in facilitating this transition by decreasing pulmonary vascular resistance. It is not known whether exogenous nitric oxide would facilitate this transition. In this study, we propose a novel approach to resuscitation of preterm infants where inhaled nitric oxide (iNO) will be used as an adjunct to oxygen with the primary goal of reducing supplemental oxygen exposure. This study is designed to be a double-blind, randomized, -placebo- controlled pilot trial with strict monitoring of parameters during transition in the delivery room.

• Study Type: Interventional
• Enrollment (Actual): 33
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma Health Sciences Center
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma, Childrens Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 minute to 2 minutes (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Infants that are 25 0/7 - 31 6/7 weeks gestation
• Infants who require Continuous Positive Airway Pressure (CPAP) or Positive Pressure Ventilation ( PPV) during delivery room resuscitation.

Exclusion Criteria:

• Refusal of consent
• Known complex congenital anomalies of the heart or lungs
• Known major genetic defects
• Hydrops fetalis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo 20ppm; Nitrogen at 20 ppm at the beginning of study start with gradual taper at 10 minutes of the study and completely off by 17 minutes of the study	Other: Nitrogen; Subjects will be randomized to receive iNO (20ppm) or nitrogen (placebo gas) with blended oxygen (starting with 0.3). Fraction of inspired oxygen will be adjusted by 0.1 increments every 15 seconds targeting pre-ductal oxygen saturation of 70-85% in the first 2 minutes of life, and then 85-93% until the end of the study period while requiring supplemental oxygen.
Experimental: Inhaled Nitric Oxide (iNO) 20 ppm; Inhaled Nitric Oxide 20 ppm at the beginning of study start with gradual taper at 10 minutes of the study and completely off by 17 minutes of the study	Drug: iNO; Immediately after birth, subjects will be randomized to receive iNO (20ppm) or nitrogen (placebo gas) with blended oxygen (starting with 0.3). Fraction of inspired oxygen will be adjusted by 0.1 increments every 15 seconds targeting pre-ductal oxygen saturation of 70-85% in the first 2 minutes of life, and then 85-93% until the end of the study period while requiring supplemental oxygen.; Other Names: Inhaled Nitric Oxide

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Factional Inspired Oxygen Percent (FiO2)	To investigate whether iNO decreases the supplemental oxygen exposure in the preterm infants who require continuous positive airway pressure (CPAP) or positive pressure ventilation (PPV) during resuscitation as per Neonatal Resuscitation Program (NRP) protocol.	20 minutes
Rate of Hyperoxia	FiO2 >60% at any 5 second increment during the study period of 20 minutes for each infant in each arm.	20 minutes
Pre and Postductal Saturation Levels	Oxygen saturations as described as preductal (right hand) as well as post ductal (either foot) and measured as percent of saturated hemoglobin by pulse oximetry.	at 20 minutes (end of study)
Heart Rate During Resuscitation	Measured and recorded heart rates every 5 seconds on study as described as beats per minute (BPM)	5, 10 and 20 minutes on study
Need for Intubation	Infants requiring placement of endotracheal tube as part of the Neonatal Resuscitation Program algorithm for airway management.	by end of study, 20 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intraventricular Hemorrhage > Grade 2	Intraventricular Hemorrhage (IVH) > Gr 2 as described by radiographic scale as described in "Incidence and evolution of subependymal and intraventricular hemorrhage: a study of infants with birth weights less than 1,500 gm.", Papile L A; Burstein J; Burstein R; Koffler H, The Journal of pediatrics, (1978 Apr) Vol. 92, No. 4, pp. 529-34. Journal code: 0375410. ISSN: 0022-3476. L-ISSN: 0022-3476. IVH classification systems Papile system Grade I Subependymal hemorrhage Grade II IVH without ventricular dilation Grade III IVH with ventricular dilation Grade IV Extensive IVH with parenchymal involvement	Hospital Discharge
Infants With Patent Ductus Arteriosus (PDA) Requiring Treatment	Count of patients requiring either pharmacologic or surgical treatment for persistent PDA	Prior to infant discharge from the hospital
Retinopathy of Prematurity (ROP)> Stage 2	Staging of any retinal disease as described by the standard screening by the American Association for Pediatric Ophthalmology and Strabismus. Only infants who survived to obtain retinal imaging are included (12 in Placebo arm and 11 in INO arm)	Prior to infant discharge from the hospital
Mechanical Ventilation, Non-invasive Ventilation (NIV), and Length of Stay in Days (LOS)	endotracheal or other airway placement and mechanical ventilation in days, days of non-invasive ventilation as described as nasal ventilation, CPAP, high flow and low flow oxygen as counted in days. Only infants who survived to discharge were included in this analysis.	Prior to infant discharge from the hospital
Bronchopulmonary Dysplasia	Bronchopulmonary Dysplasia as described as oxygen need at 36 weeks adjusted gestational age. Only infants who survived to 36 weeks gestation were included in this analysis.	at 36 weeks adjusted gestational age of participant
Late Onset Sepsis	Late Onset Sepsis as described as infection after day 5 of life. This would include all patients who survived to day of life 5.	at any time during study period

Collaborators and Investigators

• Sponsor: University of Oklahoma
• Collaborators: Mallinckrodt
• Investigators: Principal Investigator: Kris Sekar, M.D., University of Oklahoma

Study record dates

Study Major Dates

• Study Start: April 1, 2011
• Primary Completion (Actual): January 1, 2017
• Study Completion (Actual): May 1, 2017

Study Registration Dates

• First Submitted: October 7, 2010
• First Submitted That Met QC Criteria: October 12, 2010
• First Posted (Estimate): October 14, 2010

Study Record Updates

• Last Update Posted (Actual): August 19, 2020
• Last Update Submitted That Met QC Criteria: August 7, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Keywords: Prematurity; Nitric Oxide; Oxygen exposure
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Infant, Newborn, Diseases; Body Weight; Infant, Premature, Diseases; Birth Weight; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Protective Agents; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Antioxidants; Free Radical Scavengers; Endothelium-Dependent Relaxing Factors; Gasotransmitters; Nitric Oxide
• Other Study ID Numbers: 1976

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Abstract presented to The Pediatric Academic Society Meeting, May 9, 2017