Neonatal, Premature Birth, Respiratory Distress Syndrome
Conditions
Brief summary
This is a study to see if an extra 2 weeks of continuous positive airway pressure (CPAP) in stable preterm infants in the neonatal intensive care unit (NICU) can cause increased lung growth and lung function in the infants as measured at 6 months of age by pulmonary function testing.
Detailed description
This is a study to see if an extra 2 weeks of continuous positive airway pressure (CPAP) in stable preterm infants in the neonatal intensive care unit (NICU) can cause increased lung growth and lung function in the infants as measured at 6 months of age by pulmonary function testing. CPAP is a treatment widely used in the NICU in preterm infants right after they are born to help keep their lungs open/inflated. Although the benefit of CPAP after birth has been well studied, no one knows how long a stable preterm infant should stay on CPAP. The primary outcome of this study is to compare the lung volumes in the infants at 6 months of age by pulmonary function testing who were randomized to 2 extra weeks of CPAP in the NICU versus CPAP discontinuation, usual care. During the same pulmonary function test the investigators will also measure and compare how the infant's lungs diffuse gas.
Interventions
OTHERAdditional 2 weeks of CPAP
Subjects will be randomized to an additional 2 weeks of CPAP vs. discontinuing CPAP per usual care.
Sponsors
Indiana University
National Heart, Lung, and Blood Institute (NHLBI)
Cynthia McEvoy
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
1 Days to 12 Weeks
Healthy volunteers
No
Inclusion criteria
1. Infants born at \>24 to ≤ 32 weeks gestation 2. Treated with CPAP for ≥ 24 hours for respiratory distress (either as initial therapy or following extubation)
Exclusion criteria
1. Significant congenital heart disease 2. Major malformations 3. Chromosomal anomalies 4. Culture proven sepsis at consent 5. Complex maternal medical conditions 6. Clinical instability 7. Multiple gestations \> twins 8. \<3rd or \>97th percentile for weight85 9. Participating in another neonatal randomized clinical trial with a competing outcome 10. Mother/legal guardian without stable method of communication
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Alveolar Volume | 4 - 8 months of age | Establish that 2 additional weeks of CPAP in the NICU for stable preterm infants changes alveolar volume at approximately 6 months of age compared to infants who have CPAP discontinued, usual care. Measurements of alveolar volume were obtained at the same time as measurements of lung diffusion using an induced respiratory pause technique at an elevated lung volume of 30 cmH2O. During the passive expiration following the 4 second induced respiratory pause for gas exchange, carbon monoxide (CO) and helium (He) concentrations are used to calculate alveolar volume and lung diffusion. Results were expressed as averages of 2-3 measurements within 10%, adjusting for hemoglobin. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Lung Diffusion | 4 - 8 months of age | Establish that 2 extra weeks of CPAP in stable preterm infants increases lung diffusion at approximately 6 months of age versus infants who have CPAP discontinued, usual care. Measurements of lung diffusion were obtained at the same time as measurements of alveolar volume using an induced respiratory pause technique at an elevated lung volume of 30 cmH2O. During the passive expiration following the 4 second induced respiratory pause for gas exchange, carbon monoxide (CO) and helium (He) concentrations are used to calculate alveolar volume and lung diffusion. Results were expressed as averages of 2-3 measurements within 10%, adjusting for hemoglobin. |
| Forced Expiratory Flows at 50% of the Expired Volume (FEF50) | 4 - 8 months of age | Establish that 2 extra weeks of CPAP in stable preterm infants increases forced expiratory flows at approximately 6 months of age versus infants who have CPAP discontinued, usual care. Forced expiratory flows were measured using the raised volume rapid thoracic compression technique following specific American Thoracic Society and European Respiratory Society criteria for acceptance. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With the Occurrence of Wheeze | through 12 months of age (+/- 2 months) | Evaluate whether 2 extra weeks of CPAP in stable preterm infants results in lower respiratory morbidity through 12 months of age compared to infants who had CPAP discontinued, usual care. A standardized respiratory questionnaire was administered monthly through 12 months of age to ascertain this information on wheeze which was defined a priori. |
| Bayley III Gross Motor Scores | through 12 months of age (+/- 2 months) | Evaluate whether 2 extra weeks of CPAP in stable preterm infants results in improved neurodevelopmental outcomes (Bayley III Gross Motor Scores) through 12 months of age compared to infants who had CPAP discontinued, usual care. These exams were performed by a licensed psychologist in the neurodevelopmental clinic. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| eCPAP Participants randomized to stay on CPAP for 2 additional weeks once CPAP stability criteria were met. | 54 |
| dCPAP Participants randomized to discontinue CPAP once CPAP stability criteria were met. | 46 |
| Total | 100 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawn by PI after discharge due to diagnosis of a rare chromosomal mutation. | 1 | 0 |
Baseline characteristics
| Characteristic | eCPAP | Total | dCPAP |
|---|---|---|---|
| Age, Continuous | 32.4 weeks of postmenstrual age STANDARD_DEVIATION 0.9 | 32.4 weeks of postmenstrual age STANDARD_DEVIATION 0.9 | 32.4 weeks of postmenstrual age STANDARD_DEVIATION 0.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 19 Participants | 28 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 34 Participants | 71 Participants | 37 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 5 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 3 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 6 Participants | 13 Participants | 7 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) White | 42 Participants | 75 Participants | 33 Participants |
| Region of Enrollment United States | 54 participants | 100 participants | 46 participants |
| Sex: Female, Male Female | 19 Participants | 43 Participants | 24 Participants |
| Sex: Female, Male Male | 35 Participants | 57 Participants | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 54 | 0 / 46 |
| other Total, other adverse events | 37 / 54 | 29 / 46 |
| serious Total, serious adverse events | 1 / 54 | 1 / 46 |
Outcome results
Primary
Alveolar Volume
Establish that 2 additional weeks of CPAP in the NICU for stable preterm infants changes alveolar volume at approximately 6 months of age compared to infants who have CPAP discontinued, usual care. Measurements of alveolar volume were obtained at the same time as measurements of lung diffusion using an induced respiratory pause technique at an elevated lung volume of 30 cmH2O. During the passive expiration following the 4 second induced respiratory pause for gas exchange, carbon monoxide (CO) and helium (He) concentrations are used to calculate alveolar volume and lung diffusion. Results were expressed as averages of 2-3 measurements within 10%, adjusting for hemoglobin.
Time frame: 4 - 8 months of age
Population: Decrease in the number of participants analyzed versus those initially randomized due to: Seven infants in the eCPAP arm did not complete VA testing due to the following reasons: 1 diagnosed with ARID1B mutation diagnosed after discharge and discontinued from study by the principal investigator; 1 with seizure disorder so could not be sedated; 3 mothers (one with a set of twins) refused sedation for the outpatient test; 1 infant with a technically unacceptable test.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| eCPAP | Alveolar Volume | 500.2 mL | Standard Error 24.9 |
| dCPAP | Alveolar Volume | 418.1 mL | Standard Error 23.4 |
p-value: <0.0595% CI: [8.3, 155.9]Mixed Models Analysis
Secondary
Forced Expiratory Flows at 50% of the Expired Volume (FEF50)
Establish that 2 extra weeks of CPAP in stable preterm infants increases forced expiratory flows at approximately 6 months of age versus infants who have CPAP discontinued, usual care. Forced expiratory flows were measured using the raised volume rapid thoracic compression technique following specific American Thoracic Society and European Respiratory Society criteria for acceptance.
Time frame: 4 - 8 months of age
Population: Decrease in the number of participants analyzed versus those initially randomized due to: Infants in the eCPAP arm did not complete VA testing due to the following reasons: 1 diagnosed with ARID1B mutation diagnosed after discharge and discontinued from study by the principal investigator; 1 with seizure disorder so could not be sedated; 3 mothers (one with a set of twins) refused sedation for the outpatient test; and remainder with technically unacceptable test.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| eCPAP | Forced Expiratory Flows at 50% of the Expired Volume (FEF50) | 500.6 mL/sec | Standard Error 18.2 |
| dCPAP | Forced Expiratory Flows at 50% of the Expired Volume (FEF50) | 437.9 mL/sec | Standard Error 17.9 |
p-value: <0.0595% CI: [4.5, 121]Mixed Models Analysis
Secondary
Lung Diffusion
Establish that 2 extra weeks of CPAP in stable preterm infants increases lung diffusion at approximately 6 months of age versus infants who have CPAP discontinued, usual care. Measurements of lung diffusion were obtained at the same time as measurements of alveolar volume using an induced respiratory pause technique at an elevated lung volume of 30 cmH2O. During the passive expiration following the 4 second induced respiratory pause for gas exchange, carbon monoxide (CO) and helium (He) concentrations are used to calculate alveolar volume and lung diffusion. Results were expressed as averages of 2-3 measurements within 10%, adjusting for hemoglobin.
Time frame: 4 - 8 months of age
Population: Decrease in the number of participants analyzed versus those initially randomized due to: Seven infants in the eCPAP arm did not complete VA testing due to the following reasons: 1 diagnosed with ARID1B mutation diagnosed after discharge and discontinued from study by the principal investigator; 1 with seizure disorder so could not be sedated; 3 mothers (one with a set of twins) refused sedation for the outpatient test; 1 infant with a technically unacceptable test.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| eCPAP | Lung Diffusion | 3.4 mL/min/mmHg | Standard Error 0.2 |
| dCPAP | Lung Diffusion | 2.8 mL/min/mmHg | Standard Error 0.1 |
p-value: <0.0295% CI: [0.1, 1.1]Mixed Models Analysis
Other Pre-specified
Bayley III Gross Motor Scores
Evaluate whether 2 extra weeks of CPAP in stable preterm infants results in improved neurodevelopmental outcomes (Bayley III Gross Motor Scores) through 12 months of age compared to infants who had CPAP discontinued, usual care. These exams were performed by a licensed psychologist in the neurodevelopmental clinic.
Time frame: through 12 months of age (+/- 2 months)
Other Pre-specified
Number of Participants With the Occurrence of Wheeze
Evaluate whether 2 extra weeks of CPAP in stable preterm infants results in lower respiratory morbidity through 12 months of age compared to infants who had CPAP discontinued, usual care. A standardized respiratory questionnaire was administered monthly through 12 months of age to ascertain this information on wheeze which was defined a priori.
Time frame: through 12 months of age (+/- 2 months)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| eCPAP | Number of Participants With the Occurrence of Wheeze | 23 Participants |
| dCPAP | Number of Participants With the Occurrence of Wheeze | 26 Participants |
p-value: >0.0595% CI: [0.27, 1.31]Regression, Logistic
p-value: >0.0595% CI: [0.27, 1.31]Regression, Logistic