Examining the Use of Non-Invasive Inhaled Nitric Oxide to Reduce Chronic Lung Disease in Premature Newborns

Phase 2

Completed

• Conditions: Bronchopulmonary Dysplasia
• Interventions: Drug: Inhaled Nitric Oxide (iNO); Drug: Nitrogen (placebo)

• Registration Number: NCT00955487
• Lead Sponsor: University of Colorado, Denver

Brief Summary

Bronchopulmonary dysplasia (BPD) is a serious lung condition that affects premature newborns. The condition involves abnormal development of lung tissue and is characterized by inflammation and scarring in the lungs. Treatment with inhaled nitric oxide (iNO) may reduce the incidence of BPD and another commonly associated condition called pulmonary hypertension, which is high blood pressure in the vessels carrying blood to the lungs.. This study will determine if early treatment with low-dose iNO reduces the incidence of BPD, pulmonary hypertension, and death in premature newborns.

Detailed Description

BPD is a serious lung condition that primarily affects premature newborns and newborns with low birth weights. iNO has been proven to be a safe and effective treatment for pulmonary hypertension and hypoxemic respiratory failure-both of which are abnormal lung conditions-in full-term newborns. However, in babies born prematurely, the effects of iNO on lung function are not well defined. Also, previous studies have mainly examined whether iNO reduces the incidence of BPD in newborns who are on mechanical ventilation. However, intubation and mechanical ventilation of premature newborns is now increasingly being avoided, and non-invasive support, including the use of nasal continuous positive airway pressure (NCPAP), is being used. Early treatment with low-dose iNO may reduce the incidence of BPD in premature newborns who do not require mechanical ventilation and intubation after delivery. The purpose of this study is to determine if low-dose, non-invasive iNO reduces the risk of BPD, pulmonary hypertension, and death in premature newborns who do not require mechanical ventilation.

This study will enroll premature newborns who require extra oxygen but do not require intubation or mechanical ventilation for respiratory failure in the first 72 hours of life. Participants will be randomly assigned to receive low-dose, non-invasive iNO or nitrogen (placebo) during their hospital stay. While hospitalized, participants' heart rate, blood oxygen level breathing rate, blood pressure, and medications will be monitored, and blood collection will occur at various times. Monitoring will continue until participants are 30 weeks corrected gestational age or for at least 14 days if participants are born at 29 weeks or more. All participants will undergo an ultrasound of the head when they are 7 days, 28 days, and 36 weeks of age. They will undergo an echocardiogram, which is an ultrasound of the heart, at 7 and 21 days of age and 4 weeks before the original expected due date. A chest x-ray will be performed before hospital discharge, and a breathing status test will be performed either 4 weeks before participants' original expected due date or before hospital discharge. Follow-up study visits will occur at Years 1 and 2, and will include a physical examination and developmental and behavioral testing. Another echocardiogram will also be performed at the Year 1 visit.

Study Timeline

• Study Start: 2007-01
• Study First Submitted: 2009-08-06
• Study First Submitted QC: 2009-08-06
• Study First Posted: 2009-08-10
• Primary Completion: 2014-07
• Study Completion: 2014-12
• Results First Submitted: 2017-04-14
• Results First Submitted QC: 2017-04-14
• Status Verified: 2017-05
• Last Update Submitted: 2017-05-22
• Results First Posted: 2017-05-23
• Last Update Posted: 2017-06-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 124

Inclusion Criteria

• Birth weight of 500-1250 grams and gestational age of less than 34 weeks
• Age at enrollment is less than 72 hours
• Supplemental oxygen or 21% requirement by nasal cannula or NCPAP only

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Exclusion Criteria

• Presence of structural heart disease (other than patent ductus arteriosus, atrial septal defect less than 1 cm, or muscular ventricular septal defect less than 2 mm)
• Presence of lethal congenital anomaly
• Participating in another concurrent experimental study
• Requires mechanical ventilation in the first 72 hours of life (patients are not excluded if they are intubated briefly but they must be extubated at the time of consent and study entry prior to 72 hours of life)

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Inhaled Nitric Oxide (iNO)	Inhaled Nitric Oxide (iNO)	Participants will receive a low concentration of iNO until they are 30 weeks corrected gestational age or for 14 days if they were born at 29 weeks or more.
Nitrogen (placebo)	Nitrogen (placebo)	Participants will receive nitrogen (placebo) while in the hospital.

Primary Outcome Measures

Name	Time	Method
Combined Endpoint of Bronchopulmonary Dysplasia (BPD) or Mortality	Week 36 or earlier, if participants are discharged from the hospital	Number of participants that developed bronchopulmonary dysplasia and/or that died
Combined Endpoint of Bronchopulmonary Dysplasia (BPD) or Mortality Stratified by Birth Weight	Randomization to discharge	Number of participants that developed bronchopulmonary dysplasia and/or that died, stratified by birth weight (grams)

Secondary Outcome Measures

Name	Time	Method
Symptomatic PDA Requiring Surgical Ligation	Randomization through discharge	Number of participants with symptomatic PDA that required surgical ligation
Total Ventilation Days	After randomization up until hospital discharge	Of those participants who required mechanical ventilation, the total number of days receiving ventilation
Severe Intracranial Hemorrhage	Randomization to discharge	Number of participants that developed severe intracranial hemorrhage (grade 3-4)
Sepsis	Randomization to discharge	Number of participants that developed sepsis
Severity of Bronchopulmonary Dysplasia (BPD)	36 weeks corrected gestational age	Assessment of the severity of BPD as defined by the oxygen reduction test
Need for Mechanical Ventilation	Anytime after randomization up to 36 weeks corrected gestational age	Number of participants who required endotracheal intubation and mechanical ventilation
Necrotizing Enterocolitis (NEC)	After randomization through hospital discharge	Number of participants diagnosed with necrotizing enterocolitis
Symptomatic PDA Requiring Medical Treatment	From randomization until discharge	Number of participants with a symptomatic PDA that required medical treatment
Threshold Retinopathy of Prematurity (ROP)	Randomization to discharge	Threshold ROP defined as requiring interventional therapy

Trial Locations

Locations (6)

University of Alabama at Birmingham; 🇺🇸 Birmingham, Alabama, United States

Children's Hospital and University Colorado Hospital; 🇺🇸 Aurora, Colorado, United States

Anne and Robert H. Lurie Children's Hospital of Chicago and Northwestern Memorial Hospital; 🇺🇸 Chicago, Illinois, United States

Nationwide Children's Hospital; 🇺🇸 Columbus, Ohio, United States

Vanderbilt Children's Hospital; 🇺🇸 Nashville, Tennessee, United States

University of California San Diego; 🇺🇸 San Diego, California, United States