Bronchopulmonary Dysplasia
Conditions
Keywords
Inhaled Nitric Oxide, Bronchopulmonary Dysplasia, Late Prematurity, Chronic Respiratory Morbidity
Brief summary
The aim of this study is to determine if inhaled nitric oxide will improve short and long term respiratory outcomes in preterm infants. Infants born at a gestational age of 30-36 weeks and who require breathing support with high flow nasal cannula, nasal continuous positive airway pressure, or nasal intermittent positive pressure will be randomized to receive either inhaled nitric oxide or placebo. The dose will then be decreased per protocol until all respiratory support has been discontinued. Infants will be followed to evaluate safety and efficacy of non-invasive iNO delivery, up to 12 months corrected gestational age.
Interventions
DRUGinhaled nitric oxide
DRUGPlacebo Comparator - nitrogen gas
Sponsors
Mallinckrodt
Tufts Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
30 Weeks to 36 Weeks
Healthy volunteers
No
Inclusion criteria
* \<48 hours of age, * 30 - 36 weeks gestational age at birth based on best estimate using obstetrical sonography (first or second trimester), solid dating criteria, or Ballard examination, * Birth weight of ≥ 1,000 g, * 5 minute Apgar score ≥5, * Requiring nasal cannula O2 \> 1 liter per minute (LPM), continuous positive pressure (CPAP), or non invasive positive pressure ventilation (NIPPV) for treatment of respiratory failure, * Requiring a fraction of inspired oxygen (FIO2) of at least 0.25 to maintain arterial oxygen saturation (SaO2) 88-94%, * Parent or guardian has signed informed consent and agrees to all study- related procedures, including those required after hospital discharge.
Exclusion criteria
* Major congenital anomaly * Intubation and surfactant in the delivery room or prior to enrollment in the Neonatal Intensive Care Unit (NICU). Excludes intubation for suctioning. * Known congenital infection (bacterial, viral), * Perinatal asphyxia (5 minute Apgar \<5, umbilical artery pH \< 7.0 or evidence of neonatal encephalopathy), * Mother and/or infant is enrolled in another clinical trial (excluding observational) or has received an investigational drug, * Has undergone or is anticipated to require a major surgical procedure within the first 48 h of life, * Any condition which could preclude receiving study drug or performing any study-related procedures, * Use of postnatal corticosteroids, * Parent or guardian is unable or unwilling to complete study procedures after hospital discharge.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Participants Who Were Alive Without the Need for Intubation or Mechanical Ventilation Within the First Week of Life | 7 days |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Total Length of Hospital Stay | From hospital admission through discharge | participants who were followed for the duration of hospital stay |
| Total Duration of Supplemental Oxygen | From Hospital Admission through discharge | Participants were followed for the duration of hospital stay for use of supplemental oxygen |
| Number of Participants Who Had the Need for Exogenous Surfactant | 7 days | — |
| Evidence of Chronic Respiratory Morbidity at 12 Months Corrected Gestational Age (CGA) | 12 months corrected gestational age | defined by a validated system of parental diaries and pulmonary questionnaires, as well as review of medical records (medical visits, respiratory medication use, emergency room visits, and hospital re-admissions) |
| Total Duration of Respiratory Support | From hospital admission through discharge | participants were followed for the duration of hospital stay for respiratory support |
| Diagnosis of Bronchopulmonary Dysplasia (BPD) | At 36 weeks postmenstrual age or 1-2month of age | Diagnosis of BPD by oxygen challenge test at 36 weeks post menstrual age (PMA) for infants born between 30 and 32 weeks gestational age (GA). For those born 32 1/7 - 36 weeks, an oxygen challenge test was performed at 1-2 months of age. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Inhaled Nitric Oxide iNO to start at 20ppm for the first three days of life. The dose will then be decreased to 10 ppm for three days, 5 ppm for 3 days and then 2 ppm until all high flow respiratory support has been discontinued.
inhaled nitric oxide | 2 |
| Nitrogen Gas Placebo gas will be adjusted the same as study gas: to start at 20ppm for the first three days of life. The dose will then be decreased to 10 ppm for three days, 5 ppm for 3 days and then 2 ppm until all high flow respiratory support has been discontinued.
Placebo Comparator - nitrogen gas | 1 |
| Total | 3 |
Baseline characteristics
| Characteristic | Nitrogen Gas | Total | Inhaled Nitric Oxide |
|---|---|---|---|
| Age, Continuous | 1 days STANDARD_DEVIATION 0 | 1 days STANDARD_DEVIATION 0 | 1 days STANDARD_DEVIATION 0 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants | 1 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 1 Participants | 3 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 1 / 2 | 0 / 1 |
| serious Total, serious adverse events | 0 / 2 | 0 / 1 |
Outcome results
Primary
Number of Participants Who Were Alive Without the Need for Intubation or Mechanical Ventilation Within the First Week of Life
Time frame: 7 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Inhaled Nitric Oxide | Number of Participants Who Were Alive Without the Need for Intubation or Mechanical Ventilation Within the First Week of Life | 2 Participants |
| Nitrogen Gas | Number of Participants Who Were Alive Without the Need for Intubation or Mechanical Ventilation Within the First Week of Life | 1 Participants |
Secondary
Diagnosis of Bronchopulmonary Dysplasia (BPD)
Diagnosis of BPD by oxygen challenge test at 36 weeks post menstrual age (PMA) for infants born between 30 and 32 weeks gestational age (GA). For those born 32 1/7 - 36 weeks, an oxygen challenge test was performed at 1-2 months of age.
Time frame: At 36 weeks postmenstrual age or 1-2month of age
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Inhaled Nitric Oxide | Diagnosis of Bronchopulmonary Dysplasia (BPD) | 0 Participants |
| Nitrogen Gas | Diagnosis of Bronchopulmonary Dysplasia (BPD) | 0 Participants |
Secondary
Evidence of Chronic Respiratory Morbidity at 12 Months Corrected Gestational Age (CGA)
defined by a validated system of parental diaries and pulmonary questionnaires, as well as review of medical records (medical visits, respiratory medication use, emergency room visits, and hospital re-admissions)
Time frame: 12 months corrected gestational age
Population: Analysis not performed at one year corrected age, since study closed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Inhaled Nitric Oxide | Evidence of Chronic Respiratory Morbidity at 12 Months Corrected Gestational Age (CGA) | 0 Participants |
| Nitrogen Gas | Evidence of Chronic Respiratory Morbidity at 12 Months Corrected Gestational Age (CGA) | 0 Participants |
Secondary
Number of Participants Who Had the Need for Exogenous Surfactant
Time frame: 7 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Inhaled Nitric Oxide | Number of Participants Who Had the Need for Exogenous Surfactant | 0 Participants |
| Nitrogen Gas | Number of Participants Who Had the Need for Exogenous Surfactant | 0 Participants |
Secondary
Total Duration of Respiratory Support
participants were followed for the duration of hospital stay for respiratory support
Time frame: From hospital admission through discharge
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Inhaled Nitric Oxide | Total Duration of Respiratory Support | 5.5 days | Standard Deviation 1.5 |
| Nitrogen Gas | Total Duration of Respiratory Support | 4 days | Standard Deviation 0 |
Secondary
Total Duration of Supplemental Oxygen
Participants were followed for the duration of hospital stay for use of supplemental oxygen
Time frame: From Hospital Admission through discharge
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Inhaled Nitric Oxide | Total Duration of Supplemental Oxygen | 5 days | Standard Deviation 1 |
| Nitrogen Gas | Total Duration of Supplemental Oxygen | 3 days | Standard Deviation 0 |
Secondary
Total Length of Hospital Stay
participants who were followed for the duration of hospital stay
Time frame: From hospital admission through discharge
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Inhaled Nitric Oxide | Total Length of Hospital Stay | 17.5 days | Standard Deviation 2.5 |
| Nitrogen Gas | Total Length of Hospital Stay | 11 days | Standard Deviation 0 |