Bronchopulmonary Dysplasia, Chronic Lung Disease, Chronic Lung Disease of Prematurity
Conditions
Keywords
BPD, Prematurity, Supplemental Oxygen, Oximetry, Infants
Brief summary
Bronchopulmonary dysplasia (BPD), or chronic lung disease of prematurity, affects nearly half of extremely preterm infants.This study evaluates the use of supplemental oxygen to manage infants with established BPD. Participants will be randomly placed in either a higher oxygen saturation group or a lower oxygen saturation target group.
Detailed description
Bronchopulmonary Dysplasia is diagnosed only in babies who are born prematurely, and affects about half of extremely preterm infants. The incidence of BPD has increased over time. It is most commonly defined as oxygen dependence at 36 weeks postmenstrual age (PMA). Infants with BPD face more than doubled odds of death after 36 weeks PMA or disability at 5 years compared to preterm infants without BPD. BPD is associated with abnormal lung function throughout childhood and significantly increases health care costs. Cognitive and respiratory outcomes are closely linked throughout the life course; thus, optimal long--term management of BPD during infancy may ultimately improve cognitive outcomes of this high--risk population. Supplemental oxygen is a lifesaving therapy for premature infants; yet, there is limited evidence about the safety or efficacy of using supplemental oxygen to target higher versus lower oxygen saturations in infants with established BPD. Infants between the ages of 34-44 weeks post-menstrual age with moderate or severe BPD will be randomly assigned to higher or lower oxygen saturation target ranges. The study intervention will begin in the hospital and will continue at home until 6 months corrected age. When infants are discharged with supplemental oxygen, this will be titrated according to a study algorithm in order to ensure that the target saturations are maintained throughout the study period.
Interventions
OTHERLOWER oxygen saturation target group
We will randomize infants with moderate or severe BPD to lower SpO2 target ranges. The study team will then use novel technology to monitor infants starting at randomization, continuing after discharge and until 6 months corrected age, titrating supplemental oxygen to achieve these target SpO2 ranges.
OTHERHIGHER oxygen saturation target group
We will randomize infants with moderate or severe BPD to higher SpO2 target ranges. The study team will then use novel technology to monitor infants starting at randomization, continuing after discharge and until 6 months corrected age, titrating supplemental oxygen to achieve these target SpO2 ranges.
Sponsors
Thrasher Research Fund
Children's Hospital of Philadelphia
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
34 Weeks to 44 Weeks
Healthy volunteers
No
Inclusion criteria
* Pre-term males or females infants born at \<30 0/7 weeks gestation at birth * Current age 34 0/7 to 43 6/7 weeks postmenstrual age * Diagnosis of moderate or severe Bronchopulmonary Dysplasia based on the NIH consensus definition * Infant has never been discharged to home from the hospital
Exclusion criteria
* Congenital anomaly or oncologic process likely to affect growth or respiratory status * Hemoglobinopathy or other blood disorder likely to affect oxygen saturations * Contraindication to nasal cannula use (for example, severe nasal septal breakdown). * Pulmonary hypertension requiring pharmacotherapy at the time of screening/enrollment. * Tracheostomy * Intubated during entire eligibility period
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Intermittent Hypoxemia (IH) Events Per 8 Hours of Monitoring Time | Between discharge and 6 months corrected age | Incidence of intermittent hypoxia (IH, defined as SpO2 \<80% for \>=30 seconds), reported as median number of events per 8 hours of monitoring time. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Weight Z-score | Between randomization and 6 months corrected age | Change in weight Z-score. A Z-score of 0 represents average weight. Positive change in Z score indicates increasing weight relative to the population average weight. Negative change in Z score indicates decreasing weight relative to the population average weight. |
| Change in Length Z-score | Between randomization and 6 months corrected age | Change in length Z-score. A Z-score of 0 represents average length. Positive change in Z score indicates increasing length relative to the population average length. Negative change in Z score indicates decreasing length relative to the population average length. |
| Change in Head Circumference Z-score | Between randomization and 6 months corrected age | Change in head circumference (HC) Z-score. A Z-score of 0 represents average HC. Positive change in Z score indicates increasing HC relative to the population average HC. Negative change in Z score indicates decreasing HC relative to the population average HC. |
| Number of Participants With Re-hospitalization | Between discharge and 6 months corrected age | Any re-hospitalization |
| Duration of Hypoxia - Proportion of Monitored Time With Oxygen Saturation <80% | Between discharge and 6 months corrected age | Total exposure to hypoxia - proportion of monitored time with SpO2 \<80% |
| Number of Participants With Visits to Emergency Room or Urgent Care for Respiratory Reasons | Between discharge and 6 months corrected age | Any visits to ER or urgent care for respiratory health-related problems |
| Feeding | At 6 months corrected age | Quality of infant oral feeding skills, parent reports that the child's feeding times are stressful or very stressful for themselves |
| Development | At 6 months corrected age | Bayley Scales of Infant Development screening test, which is a standardized assessment of cognitive, motor, and language development in infancy and early childhood. Outcome will be reported as number of children considered at risk in any domain. |
| Number of Participants With Respiratory Medication Use | At 6 months corrected age | Number of patients with inhaled respiratory medication use |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| LOWER Oxygen Saturation Target Group Oxygen saturation (SpO2) target range 90--94%. The study intervention will begin in the hospital and will continue at home until 6 months corrected age (CA). Overnight continuous oximetry will be transmitted wirelessly to the study team. In hospital, inspired oxygen will be adjusted as needed to maintain target SpO2. Monitoring will continue after discharge, and oxygen flow will be titrated monthly according to a standardized algorithm.
LOWER oxygen saturation target group: We will randomize infants with moderate or severe BPD to lower SpO2 target ranges. The study team will then use novel technology to monitor infants starting at randomization, continuing after discharge and until 6 months corrected age, titrating supplemental oxygen to achieve these target SpO2 ranges. | 28 |
| HIGHER Oxygen Saturation Target Group Oxygen saturation target range greater than or equal to 96%.The study intervention will begin in the hospital and will continue at home until 6 months CA. Overnight continuous oximetry will be transmitted wirelessly to the study team. In hospital, inspired oxygen will be adjusted as needed to maintain target SpO2. Monitoring will continue after discharge, and oxygen flow will be titrated monthly according to a standardized algorithm.
HIGHER oxygen saturation target group: We will randomize infants with moderate or severe BPD to higher SpO2 target ranges. The study team will then use novel technology to monitor infants starting at randomization, continuing after discharge and until 6 months corrected age, titrating supplemental oxygen to achieve these target SpO2 ranges. | 22 |
| Total | 50 |
Baseline characteristics
| Characteristic | HIGHER Oxygen Saturation Target Group | Total | LOWER Oxygen Saturation Target Group |
|---|---|---|---|
| Age, Continuous | 40.5 post-menstrual age (PMA) in weeks STANDARD_DEVIATION 2.2 | 40.2 post-menstrual age (PMA) in weeks STANDARD_DEVIATION 2.3 | 39.9 post-menstrual age (PMA) in weeks STANDARD_DEVIATION 2.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 5 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 20 Participants | 45 Participants | 25 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 15 Participants | 34 Participants | 19 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 2 Participants | 1 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 | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 5 Participants | 12 Participants | 7 Participants |
| Sex: Female, Male Female | 9 Participants | 23 Participants | 14 Participants |
| Sex: Female, Male Male | 13 Participants | 27 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 28 | 0 / 22 |
| other Total, other adverse events | 0 / 28 | 0 / 22 |
| serious Total, serious adverse events | 0 / 28 | 0 / 22 |
Outcome results
Primary
Intermittent Hypoxemia (IH) Events Per 8 Hours of Monitoring Time
Incidence of intermittent hypoxia (IH, defined as SpO2 \<80% for \>=30 seconds), reported as median number of events per 8 hours of monitoring time.
Time frame: Between discharge and 6 months corrected age
Population: Infants with sufficient oximetry data were included in primary outcome analyses.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| LOWER Oxygen Saturation Target Group | Intermittent Hypoxemia (IH) Events Per 8 Hours of Monitoring Time | 2.2 IH events per 8 hours of monitoring time |
| HIGHER Oxygen Saturation Target Group | Intermittent Hypoxemia (IH) Events Per 8 Hours of Monitoring Time | 1.2 IH events per 8 hours of monitoring time |
Secondary
Change in Head Circumference Z-score
Change in head circumference (HC) Z-score. A Z-score of 0 represents average HC. Positive change in Z score indicates increasing HC relative to the population average HC. Negative change in Z score indicates decreasing HC relative to the population average HC.
Time frame: Between randomization and 6 months corrected age
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| LOWER Oxygen Saturation Target Group | Change in Head Circumference Z-score | 0.5 delta Z-score | Standard Deviation 1.3 |
| HIGHER Oxygen Saturation Target Group | Change in Head Circumference Z-score | 0.4 delta Z-score | Standard Deviation 1.7 |
Secondary
Change in Length Z-score
Change in length Z-score. A Z-score of 0 represents average length. Positive change in Z score indicates increasing length relative to the population average length. Negative change in Z score indicates decreasing length relative to the population average length.
Time frame: Between randomization and 6 months corrected age
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| LOWER Oxygen Saturation Target Group | Change in Length Z-score | 1.7 delta Z-score | Standard Deviation 1.3 |
| HIGHER Oxygen Saturation Target Group | Change in Length Z-score | 1.2 delta Z-score | Standard Deviation 1.4 |
Secondary
Change in Weight Z-score
Change in weight Z-score. A Z-score of 0 represents average weight. Positive change in Z score indicates increasing weight relative to the population average weight. Negative change in Z score indicates decreasing weight relative to the population average weight.
Time frame: Between randomization and 6 months corrected age
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| LOWER Oxygen Saturation Target Group | Change in Weight Z-score | 0.6 delta Z-score | Standard Deviation 1.4 |
| HIGHER Oxygen Saturation Target Group | Change in Weight Z-score | 0.5 delta Z-score | Standard Deviation 1.2 |
Secondary
Development
Bayley Scales of Infant Development screening test, which is a standardized assessment of cognitive, motor, and language development in infancy and early childhood. Outcome will be reported as number of children considered at risk in any domain.
Time frame: At 6 months corrected age
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| LOWER Oxygen Saturation Target Group | Development | 8 Participants |
| HIGHER Oxygen Saturation Target Group | Development | 3 Participants |
Secondary
Duration of Hypoxia - Proportion of Monitored Time With Oxygen Saturation <80%
Total exposure to hypoxia - proportion of monitored time with SpO2 \<80%
Time frame: Between discharge and 6 months corrected age
Population: Analysis includes infant with sufficient oximetry data
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| LOWER Oxygen Saturation Target Group | Duration of Hypoxia - Proportion of Monitored Time With Oxygen Saturation <80% | 0.005 proportion of monitored time |
| HIGHER Oxygen Saturation Target Group | Duration of Hypoxia - Proportion of Monitored Time With Oxygen Saturation <80% | 0.004 proportion of monitored time |
Secondary
Feeding
Quality of infant oral feeding skills, parent reports that the child's feeding times are stressful or very stressful for themselves
Time frame: At 6 months corrected age
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| LOWER Oxygen Saturation Target Group | Feeding | 1 Participants |
| HIGHER Oxygen Saturation Target Group | Feeding | 0 Participants |
Secondary
Number of Participants With Re-hospitalization
Any re-hospitalization
Time frame: Between discharge and 6 months corrected age
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| LOWER Oxygen Saturation Target Group | Number of Participants With Re-hospitalization | 9 Participants |
| HIGHER Oxygen Saturation Target Group | Number of Participants With Re-hospitalization | 6 Participants |
Secondary
Number of Participants With Respiratory Medication Use
Number of patients with inhaled respiratory medication use
Time frame: At 6 months corrected age
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| LOWER Oxygen Saturation Target Group | Number of Participants With Respiratory Medication Use | 6 Participants |
| HIGHER Oxygen Saturation Target Group | Number of Participants With Respiratory Medication Use | 6 Participants |
Secondary
Number of Participants With Visits to Emergency Room or Urgent Care for Respiratory Reasons
Any visits to ER or urgent care for respiratory health-related problems
Time frame: Between discharge and 6 months corrected age
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| LOWER Oxygen Saturation Target Group | Number of Participants With Visits to Emergency Room or Urgent Care for Respiratory Reasons | 5 Participants |
| HIGHER Oxygen Saturation Target Group | Number of Participants With Visits to Emergency Room or Urgent Care for Respiratory Reasons | 2 Participants |