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

Respiratory Distress Syndrome in Premature Infants Clinical Trial

— iNO  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01220687
• Other study ID #: 1976
• Status: Completed
• Phase: N/A
• Start date: April 2011
• Est. completion date: May 1, 2017

Study information

• Verified date: August 2020
• Source: University of Oklahoma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 33
• Est. completion date: May 1, 2017
• Est. primary completion date: January 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 2 Minutes

Eligibility

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

Related Conditions & MeSH terms

• Birth Weight
• Respiratory Distress Syndrome in Premature Infants
• Respiratory Distress Syndrome, Adult
• Respiratory Distress Syndrome, Newborn
• Very Low Birth Weight Baby

Intervention

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:
• 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.

Locations

Country	Name	City	State
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	University of Oklahoma, Childrens Hospital	Oklahoma City	Oklahoma

Sponsors (2)

Lead Sponsor	Collaborator
University of Oklahoma	Mallinckrodt

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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)
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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