Bronchopulmonary Dysplasia, Respiratory Distress Syndrome
Conditions
Keywords
Continuous positive airway pressure, Prematurity, Respiratory distress syndrome, Bronchopulmonary dysplasia
Brief summary
The primary aim of this study is to quantify and compare changes in lung volumes (as measured by functional residual capacity) in premature infants stable on continuous positive airway pressure (CPAP), and then randomized to two additional weeks of CPAP and room air versus room air alone. We hypothesize that infants randomized to additional CPAP will demonstrate an increased functional residual capacity (at the end of the two week study period and prior to discharge) compared to those randomized to room air.
Interventions
DEVICECPAP and room air
Stable premature infants on CPAP and room air and meeting specific stability criteria will be randomized to stay on continuous positive airway pressure and room air for an additional two weeks or will be transitioned to room air alone.
Sponsors
Oregon Health and Science University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
No minimum to 1 Years
Healthy volunteers
No
Inclusion criteria
* Gestational age at birth \<33 weeks * Required CPAP for a minimum of 24 hours for respiratory distress * Patient on CPAP and room air at time of randomization
Exclusion criteria
* Complex congenital heart disease other than patent ductus arteriosus or atrial septal defect * Major malformations or chromosomal anomalies * Multiple gestation greater than twins * Culture proven sepsis or unstable at time of randomization
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes in the Measurements of Functional Residual Capacity (FRC) in Randomized Premature Infants | Just prior to randomization, two weeks later and at discharge (an average of 34 to 37 weeks of corrected gestational age). | Functional residual capacity (FRC) was measured with the nitrogen washout technique. For the nitrogen washout technique, calibration is done with 2 known volumes, and a calibration line was constructed for the system at the specific flow rate and used to correlate the nitrogen washed out to the infant's FRC. The system corrected for dead space and corrected the FRC to body temperature, pressure, and water-saturated conditions. Acceptance criteria included: 1) infant supine and quietly asleep; 2) test initiated at end expiration; 3) no evidence of leak on tracing of the washout; 4) consistent tracings; 5) at least 2-3 measurements with a coefficient of variation \<10%. These are testing and acceptance criteria outlined by the American Thoracic Society and European Respiratory Society. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Measurements of Passive Respiratory Compliance in Randomized Premature Infants | Just before randomization, two weeks later, and at discharge at about 35-37 weeks of corrected gestational age | Measurements of passive respiratory compliance will be done with the single breath occlusion technique. |
| Passive Respiratory Resistance in Randomized Premature Infants | Just prior to randomization, two weeks after randomization, and at discharge at about 35-37 weeks of corrected gestational age. | Measurements of passive respiratory resistance will be done with the single breath occlusion technique. |
| Measurements of Tidal Flow Volume Loops Will be Done in the Randomized Premature Infants. | Just before randomization, two weeks later, and at discharge at about 35-37 weeks of corrected gestational age. | Characteristics of tidal flow volume loops will be measured. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Cost Comparison Between Randomized Groups | Through 12 months of corrected age | Cost comparison through 12 months of corrected gestational age between the randomized groups per percent improvement in FRC measured at discharge between the groups. |
| Changes in the Growth Parameters Between the Randomized Premature Infants | From randomization through discharge at about 35-37 weeks of corrected gestational age. | Changes in growth parameters will be compared between randomized groups. |
| Days in the Hospital | Delivery through discharge at about 35-37 weeks of corrected gestational age | The days in the hospital will be compared between the randomized groups. |
| Days on Oxygen Between the Randomized Groups | Through discharge at about 35-37 weeks of corrected gestational age | The days of oxygen supplementation will be compared between the groups of randomized patients. |
| The Number of Participants With Adverse Events and Serious Adverse Events in the Randomized Groups of Premature Infants. | From randomization through discharge from the neonatal intensive care unit (an average of 35 to 37 weeks of corrected gestational age). | Adverse events and serious adverse events occurring in the randomized groups will be documented carefully |
| Corrected Gestational Age at Which Full Nipple Feeds Are Achieved | Randomization through discharge at about 35-37 weeks of corrected gestational age. | The corrected gestational age at which full nipple feeds are achieved will be compared between the randomized groups. |
| Incidence of Wheezing Through One Year of Age | Discharge through one year of corrected age | Incidence of wheezing will be compared through one year of corrected gestational age between the randomized groups. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Active Comparator: CPAP and Room Air CPAP and room air: Stable premature infants on CPAP and room air and meeting specific stability criteria will be randomized to stay on continuous positive airway pressure and room air for an additional two weeks or will be transitioned to room air alone. | 22 |
| No Intervention: Room Air Premature stable infants on CPAP and room air will be randomized to transition to room air alone. | 22 |
| Total | 44 |
Baseline characteristics
| Characteristic | Total | Active Comparator: CPAP and Room Air | No Intervention: Room Air |
|---|---|---|---|
| Age, Categorical <=18 years | 44 Participants | 22 Participants | 22 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment United States | 44 Participants | 22 Participants | 22 Participants |
| Sex: Female, Male Female | 21 Participants | 13 Participants | 8 Participants |
| Sex: Female, Male Male | 23 Participants | 9 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 24 | 0 / 26 |
| other Total, other adverse events | 0 / 24 | 0 / 26 |
| serious Total, serious adverse events | 0 / 24 | 0 / 26 |
Outcome results
Primary
Changes in the Measurements of Functional Residual Capacity (FRC) in Randomized Premature Infants
Functional residual capacity (FRC) was measured with the nitrogen washout technique. For the nitrogen washout technique, calibration is done with 2 known volumes, and a calibration line was constructed for the system at the specific flow rate and used to correlate the nitrogen washed out to the infant's FRC. The system corrected for dead space and corrected the FRC to body temperature, pressure, and water-saturated conditions. Acceptance criteria included: 1) infant supine and quietly asleep; 2) test initiated at end expiration; 3) no evidence of leak on tracing of the washout; 4) consistent tracings; 5) at least 2-3 measurements with a coefficient of variation \<10%. These are testing and acceptance criteria outlined by the American Thoracic Society and European Respiratory Society.
Time frame: Just prior to randomization, two weeks later and at discharge (an average of 34 to 37 weeks of corrected gestational age).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CPAP and Room Air | Changes in the Measurements of Functional Residual Capacity (FRC) in Randomized Premature Infants | FRC change from baseline to two weeks | 12.6 mL | Standard Deviation 11.4 |
| CPAP and Room Air | Changes in the Measurements of Functional Residual Capacity (FRC) in Randomized Premature Infants | FRC change from baseline to discharge | 27.2 mL | Standard Deviation 12.5 |
| Room Air | Changes in the Measurements of Functional Residual Capacity (FRC) in Randomized Premature Infants | FRC change from baseline to two weeks | 6.4 mL | Standard Deviation 10.1 |
| Room Air | Changes in the Measurements of Functional Residual Capacity (FRC) in Randomized Premature Infants | FRC change from baseline to discharge | 17.1 mL | Standard Deviation 11.7 |
Comparison: FRC values over time were modeled using linear mixed effects regression with treatment group vs. time interaction and repeated measures for the randomization, 2 week, and discharge time points. Compound symmetric covariance structures were used to account for the correlation of FRC values within each patient. We compared outcomes between the two treatment groups and included adjustments for gender, twin gestation, and weight at randomization.p-value: <0.0595% CI: [0.02, 13.22]Regression, Linear
Secondary
Measurements of Passive Respiratory Compliance in Randomized Premature Infants
Measurements of passive respiratory compliance will be done with the single breath occlusion technique.
Time frame: Just before randomization, two weeks later, and at discharge at about 35-37 weeks of corrected gestational age
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CPAP and Room Air | Measurements of Passive Respiratory Compliance in Randomized Premature Infants | At Randomization | 1.37 mL/Kg | Standard Deviation 0.28 |
| CPAP and Room Air | Measurements of Passive Respiratory Compliance in Randomized Premature Infants | At End of 2 Weeks of Treatment | 1.28 mL/Kg | Standard Deviation 0.28 |
| CPAP and Room Air | Measurements of Passive Respiratory Compliance in Randomized Premature Infants | At Discharge | 1.08 mL/Kg | Standard Deviation 0.18 |
| Room Air | Measurements of Passive Respiratory Compliance in Randomized Premature Infants | At Randomization | 1.32 mL/Kg | Standard Deviation 0.28 |
| Room Air | Measurements of Passive Respiratory Compliance in Randomized Premature Infants | At End of 2 Weeks of Treatment | 1.17 mL/Kg | Standard Deviation 0.18 |
| Room Air | Measurements of Passive Respiratory Compliance in Randomized Premature Infants | At Discharge | 1.12 mL/Kg | Standard Deviation 0.21 |
p-value: >0.05t-test, 2 sided
Comparison: Group differences in the secondary outcomes were tested at randomization, two weeks, and discharge using independent samples t-tests.
Secondary
Measurements of Tidal Flow Volume Loops Will be Done in the Randomized Premature Infants.
Characteristics of tidal flow volume loops will be measured.
Time frame: Just before randomization, two weeks later, and at discharge at about 35-37 weeks of corrected gestational age.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CPAP and Room Air | Measurements of Tidal Flow Volume Loops Will be Done in the Randomized Premature Infants. | At Randomization | 7.1 mL | Standard Deviation 1.1 |
| CPAP and Room Air | Measurements of Tidal Flow Volume Loops Will be Done in the Randomized Premature Infants. | At End of 2 Weeks of Treatment | 7.6 mL | Standard Deviation 1.1 |
| CPAP and Room Air | Measurements of Tidal Flow Volume Loops Will be Done in the Randomized Premature Infants. | At Discharge | 7.3 mL | Standard Deviation 1.1 |
| Room Air | Measurements of Tidal Flow Volume Loops Will be Done in the Randomized Premature Infants. | At Randomization | 7.8 mL | Standard Deviation 0.97 |
| Room Air | Measurements of Tidal Flow Volume Loops Will be Done in the Randomized Premature Infants. | At End of 2 Weeks of Treatment | 7.4 mL | Standard Deviation 0.9 |
| Room Air | Measurements of Tidal Flow Volume Loops Will be Done in the Randomized Premature Infants. | At Discharge | 7.3 mL | Standard Deviation 0.56 |
Secondary
Passive Respiratory Resistance in Randomized Premature Infants
Measurements of passive respiratory resistance will be done with the single breath occlusion technique.
Time frame: Just prior to randomization, two weeks after randomization, and at discharge at about 35-37 weeks of corrected gestational age.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CPAP and Room Air | Passive Respiratory Resistance in Randomized Premature Infants | At Randomization | 0.054 cmH2O/mL/sec | Standard Deviation 0.014 |
| CPAP and Room Air | Passive Respiratory Resistance in Randomized Premature Infants | At End of 2 Weeks of Treatment | 0.061 cmH2O/mL/sec | Standard Deviation 0.014 |
| CPAP and Room Air | Passive Respiratory Resistance in Randomized Premature Infants | At Discharge | 0.073 cmH2O/mL/sec | Standard Deviation 0.02 |
| Room Air | Passive Respiratory Resistance in Randomized Premature Infants | At Randomization | 0.053 cmH2O/mL/sec | Standard Deviation 0.009 |
| Room Air | Passive Respiratory Resistance in Randomized Premature Infants | At End of 2 Weeks of Treatment | 0.074 cmH2O/mL/sec | Standard Deviation 0.021 |
| Room Air | Passive Respiratory Resistance in Randomized Premature Infants | At Discharge | 0.082 cmH2O/mL/sec | Standard Deviation 0.022 |
Other Pre-specified
Changes in the Growth Parameters Between the Randomized Premature Infants
Changes in growth parameters will be compared between randomized groups.
Time frame: From randomization through discharge at about 35-37 weeks of corrected gestational age.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CPAP and Room Air | Changes in the Growth Parameters Between the Randomized Premature Infants | At Discharge | 2282 g | Standard Deviation 354 |
| CPAP and Room Air | Changes in the Growth Parameters Between the Randomized Premature Infants | At Randomization | 1567 g | Standard Deviation 293 |
| Room Air | Changes in the Growth Parameters Between the Randomized Premature Infants | At Randomization | 1482 g | Standard Deviation 323 |
| Room Air | Changes in the Growth Parameters Between the Randomized Premature Infants | At Discharge | 2253 g | Standard Deviation 413 |
Other Pre-specified
Corrected Gestational Age at Which Full Nipple Feeds Are Achieved
The corrected gestational age at which full nipple feeds are achieved will be compared between the randomized groups.
Time frame: Randomization through discharge at about 35-37 weeks of corrected gestational age.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| CPAP and Room Air | Corrected Gestational Age at Which Full Nipple Feeds Are Achieved | 35.9 weeks |
| Room Air | Corrected Gestational Age at Which Full Nipple Feeds Are Achieved | 35.5 weeks |
Other Pre-specified
Cost Comparison Between Randomized Groups
Cost comparison through 12 months of corrected gestational age between the randomized groups per percent improvement in FRC measured at discharge between the groups.
Time frame: Through 12 months of corrected age
Population: Data not collected
Other Pre-specified
Days in the Hospital
The days in the hospital will be compared between the randomized groups.
Time frame: Delivery through discharge at about 35-37 weeks of corrected gestational age
Population: Data not collected
Other Pre-specified
Days on Oxygen Between the Randomized Groups
The days of oxygen supplementation will be compared between the groups of randomized patients.
Time frame: Through discharge at about 35-37 weeks of corrected gestational age
| Arm | Measure | Value (MEAN) |
|---|---|---|
| CPAP and Room Air | Days on Oxygen Between the Randomized Groups | 0 days |
| Room Air | Days on Oxygen Between the Randomized Groups | 0 days |
Other Pre-specified
Incidence of Wheezing Through One Year of Age
Incidence of wheezing will be compared through one year of corrected gestational age between the randomized groups.
Time frame: Discharge through one year of corrected age
Population: Number of participants analyzed is lower here as we were not able to follow all infants through 1 year of corrected age.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CPAP and Room Air | Incidence of Wheezing Through One Year of Age | 7 Participants |
| Room Air | Incidence of Wheezing Through One Year of Age | 6 Participants |
Other Pre-specified
The Number of Participants With Adverse Events and Serious Adverse Events in the Randomized Groups of Premature Infants.
Adverse events and serious adverse events occurring in the randomized groups will be documented carefully
Time frame: From randomization through discharge from the neonatal intensive care unit (an average of 35 to 37 weeks of corrected gestational age).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CPAP and Room Air | The Number of Participants With Adverse Events and Serious Adverse Events in the Randomized Groups of Premature Infants. | 0 participants |
| Room Air | The Number of Participants With Adverse Events and Serious Adverse Events in the Randomized Groups of Premature Infants. | 0 participants |