A Phase 2 interventional study of Inhaled Nitric Oxide (iNO) and Nitrogen (placebo) in Bronchopulmonary Dysplasia, sponsored by University of Colorado, Denver. Completed at 6 sites in United States. Open to participants aged Up to 72 Hours. Per ClinicalTrials.gov, last updated 2017-06-15.
Sponsored by University of Colorado, Denver · Phase 2, Interventional, and Prevention
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.
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.
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This study's enrollment of 124 is above the median of 72 across 2,118 interventional studies indexed under Lung Diseases.
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Of its 139 completed or terminated interventional studies of FDA-regulated products, 89 (64%) have results posted.
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Exclusion Criteria:
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.
Drug: Inhaled Nitric Oxide (iNO)
Participants will receive nitrogen (placebo) while in the hospital.
Drug: Nitrogen (placebo)
iNO will be delivered using the iNOVent device to provide 10 ppm proximally (yielding approximately 5 ppm to the posterior pharynx).
Nitrogen will be delivered using the iNOVent device to provide 10 ppm proximally (yielding approximately 5 ppm to the posterior pharynx).
Combined Endpoint of Bronchopulmonary Dysplasia (BPD) or Mortality
Number of participants that developed bronchopulmonary dysplasia and/or that died
Time frame: Week 36 or earlier, if participants are discharged from the hospital
Combined Endpoint of Bronchopulmonary Dysplasia (BPD) or Mortality Stratified by Birth Weight
Number of participants that developed bronchopulmonary dysplasia and/or that died, stratified by birth weight (grams)
Time frame: Randomization to discharge
Severity of Bronchopulmonary Dysplasia (BPD)
Assessment of the severity of BPD as defined by the oxygen reduction test
Time frame: 36 weeks corrected gestational age
Need for Mechanical Ventilation
Number of participants who required endotracheal intubation and mechanical ventilation
Time frame: Anytime after randomization up to 36 weeks corrected gestational age
Total Ventilation Days
Of those participants who required mechanical ventilation, the total number of days receiving ventilation
Time frame: After randomization up until hospital discharge
Necrotizing Enterocolitis (NEC)
Number of participants diagnosed with necrotizing enterocolitis
Time frame: After randomization through hospital discharge
Symptomatic PDA Requiring Medical Treatment
Number of participants with a symptomatic PDA that required medical treatment
Time frame: From randomization until discharge
Symptomatic PDA Requiring Surgical Ligation
Number of participants with symptomatic PDA that required surgical ligation
Time frame: Randomization through discharge
Threshold Retinopathy of Prematurity (ROP)
Threshold ROP defined as requiring interventional therapy
Time frame: Randomization to discharge
Severe Intracranial Hemorrhage
Number of participants that developed severe intracranial hemorrhage (grade 3-4)
Time frame: Randomization to discharge
Sepsis
Number of participants that developed sepsis
Time frame: Randomization to discharge
Days in Hospital
Length of stay of participants
Time frame: From birth to hospital discharge
| Milestone | 500-749g Inhaled Nitric Oxide (iNO) | 500-749g Placebo (Nitrogen) | 750-999g Inhaled Nitric Oxide (iNO) | 750-999g Placebo (Nitrogen) | 1000-1250g Inhaled Nitric Oxide (iNO) | 1000-1250g Placebo (Nitrogen) |
|---|---|---|---|---|---|---|
| Started | 10 | 9 | 17 | 21 | 32 | 35 |
| Completed | 10 | 9 | 17 | 21 | 32 | 35 |
| Not completed | 0 | 0 | 0 | 0 | 0 | 0 |
Number of participants that developed bronchopulmonary dysplasia and/or that died
| Participants | Inhaled Nitric Oxide (iNO) | Placebo (Nitrogen) |
|---|---|---|
| Death | 1 | 2 |
| Bronchopulmonary Dysplasia (BPD) | 24 | 25 |
| Death/BPD | 25 | 26 |
| No Death or BPD | 9 | 12 |
Number of participants that developed bronchopulmonary dysplasia and/or that died, stratified by birth weight (grams)
| Participants | 500-749g Inhaled Nitric Oxide (iNO) | 500-749g Placebo (Nitrogen) | 750-999g Inhaled Nitric Oxide (iNO) | 750-999g Placebo (Nitrogen) | 1000-1250g Inhaled Nitric Oxide (iNO) | 1000-1250g Placebo (Nitrogen) |
|---|---|---|---|---|---|---|
| Death | 0 | 2 | 1 | 0 | 0 | 0 |
| BPD | 3 | 4 | 8 | 6 | 13 | 15 |
| Death/BPD | 3 | 5 | 9 | 6 | 13 | 15 |
Assessment of the severity of BPD as defined by the oxygen reduction test
| Participants | Inhaled Nitric Oxide (iNO) | Placebo (Nitrogen) |
|---|---|---|
| None | 35 | 37 |
| Mild | 2 | 9 |
| Moderate | 20 | 12 |
| Severe | 2 | 4 |
Number of participants who required endotracheal intubation and mechanical ventilation
| Participants | Inhaled Nitric Oxide (iNO) | Placebo (Nitrogen) |
|---|---|---|
| Required Mechanical Ventilation | 13 | 15 |
| Did not require mechanical ventilation | 46 | 50 |
Of those participants who required mechanical ventilation, the total number of days receiving ventilation
| Days | Inhaled Nitric Oxide (iNO) | Placebo (Nitrogen) |
|---|---|---|
| Total Ventilation Days | 9.7 ± 29 | 8.4 ± 12 |
Number of participants diagnosed with necrotizing enterocolitis
| Participants | Inhaled Nitric Oxide (iNO) | Placebo (Nitrogen) |
|---|---|---|
| Necrotizing Enterocolitis (NEC) | 5 | 10 |
Number of participants with a symptomatic PDA that required medical treatment
| Participants | Inhaled Nitric Oxide (iNO) | Placebo (Nitrogen) |
|---|---|---|
| Symptomatic PDA Requiring Medical Treatment | 1 | 2 |
Number of participants with symptomatic PDA that required surgical ligation
| Participants | Inhaled Nitric Oxide (iNO) | Placebo (Nitrogen) |
|---|---|---|
| Symptomatic PDA Requiring Surgical Ligation | 3 | 8 |
Threshold ROP defined as requiring interventional therapy
| Participants | Inhaled Nitric Oxide (iNO) | Placebo (Nitrogen) |
|---|---|---|
| Threshold Retinopathy of Prematurity (ROP) | 3 | 4 |
Number of participants that developed severe intracranial hemorrhage (grade 3-4)
| Participants | Inhaled Nitric Oxide (iNO) | Placebo (Nitrogen) |
|---|---|---|
| Severe Intracranial Hemorrhage | 2 | 4 |
Number of participants that developed sepsis
| Participants | Inhaled Nitric Oxide (iNO) | Placebo (Nitrogen) |
|---|---|---|
| Sepsis | 13 | 14 |
Length of stay of participants
| Days | Inhaled Nitric Oxide (iNO) | Placebo (Nitrogen) |
|---|---|---|
| Days in Hospital | 75 ± 32 | 75 ± 29 |
Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Inhaled Nitric Oxide (iNO) | 2/59 (3.4%) | 27/59 (45.8%) | 0/59 (0%) |
| Placebo (Nitrogen) | 4/65 (6.2%) | 42/65 (64.6%) | 0/65 (0%) |
| Event | Inhaled Nitric Oxide (iNO) | Placebo (Nitrogen) |
|---|---|---|
| SepsisInfections and infestations | 13/59 | 14/65 |
| Necrotizing enterocolitisGastrointestinal disorders | 5/59 | 10/65 |
| Symptomatic PDACardiac disorders | 3/59 | 8/65 |
| Threshold ROPEye disorders | 3/59 | 4/65 |
| Severe ICHNervous system disorders | 2/59 | 4/65 |
| Symptomatic PDACardiac disorders | 1/59 | 2/65 |
| Age, Customized(Weeks) | Inhaled Nitric Oxide (iNO) | Placebo (Nitrogen) | Total |
|---|---|---|---|
| Gestational Age at Baseline | 27.5 ± 1.6 | 27.3 ± 1.8 | 27.4 ± 1.7 |
| Sex: Female, Male(Participants) | Inhaled Nitric Oxide (iNO) | Placebo (Nitrogen) | Total |
|---|---|---|---|
| Female | 35 | 34 | 69 |
| Male | 24 | 31 | 55 |
| Race/Ethnicity, Customized(Participants) | Inhaled Nitric Oxide (iNO) | Placebo (Nitrogen) | Total |
|---|---|---|---|
| White | 48 | 48 | 96 |
| Black | 8 | 11 | 19 |
| Other | 3 | 6 | 9 |
| Region of Enrollment(Participants) | Inhaled Nitric Oxide (iNO) | Placebo (Nitrogen) | Total |
|---|---|---|---|
| United States | 59 | 65 | 124 |
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University of Colorado, Denver