Clinical trial NCT00955487: Examining the Use of Non-Invasive Inhaled Nitric Oxide to Reduce Chronic Lung Disease in Premature Newborns
Official title: Examining the Use of Non-Invasive Inhaled Nitric Oxide to Reduce Chronic Lung Disease in Premature Newborns
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Bronchopulmonary Dysplasia
Keywords: Premature Newborns
Inhaled Nitric Oxide
Lead sponsor: University of Colorado, Denver
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2009-08-10
Enrollment: 124
Sex: ALL
Maximum age (years): 72
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility criteria: 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

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)

Primary outcomes:
measure: Combined Endpoint of Bronchopulmonary Dysplasia (BPD) or Mortality
timeFrame: Week 36 or earlier, if participants are discharged from the hospital
measure: Combined Endpoint of Bronchopulmonary Dysplasia (BPD) or Mortality Stratified by Birth Weight
timeFrame: Randomization to discharge
Secondary outcomes:
measure: Severity of Bronchopulmonary Dysplasia (BPD)
timeFrame: 36 weeks corrected gestational age
measure: Need for Mechanical Ventilation
timeFrame: Anytime after randomization up to 36 weeks corrected gestational age
measure: Total Ventilation Days
timeFrame: After randomization up until hospital discharge
measure: Necrotizing Enterocolitis (NEC)
timeFrame: After randomization through hospital discharge
measure: Symptomatic PDA Requiring Medical Treatment
timeFrame: From randomization until discharge
measure: Symptomatic PDA Requiring Surgical Ligation
timeFrame: Randomization through discharge
measure: Threshold Retinopathy of Prematurity (ROP)
timeFrame: Randomization to discharge
measure: Severe Intracranial Hemorrhage
timeFrame: Randomization to discharge
measure: Sepsis
timeFrame: Randomization to discharge
Other outcomes:
measure: Days in Hospital
timeFrame: From birth to hospital discharge
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: San Diego
country: United States
facility: University of California San Diego
state: California
city: Aurora
country: United States
facility: Children's Hospital and University Colorado Hospital
state: Colorado
city: Chicago
country: United States
facility: Anne and Robert H. Lurie Children's Hospital of Chicago and Northwestern Memorial Hospital
state: Illinois
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Nashville
country: United States
facility: Vanderbilt Children's Hospital
state: Tennessee
Study officials:
affiliation: Chidlren's Hospital and University of Colorado Hospital
name: John Kinsella, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kinsella JP, Cutter GR, Steinhorn RH, Nelin LD, Walsh WF, Finer NN, Abman SH. Noninvasive inhaled nitric oxide does not prevent bronchopulmonary dysplasia in premature newborns. J Pediatr. 2014 Dec;165(6):1104-1108.e1. doi: 10.1016/j.jpeds.2014.06.018. Epub 2014 Jul 22.