Duration of Continuous Positive Airway Pressure and Pulmonary Function Testing in Preterm Infants

• Sponsor: Oregon Health and Science University (Other)
• Overall Status: Completed
• CT.gov ID: NCT02249143
• Collaborator: (none)
• Enrollment: 50
• Location: 1
• Arms: 2
• Actual Duration (Months): 36
• Patients Per Site Per Month: 1.4

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Respiratory Distress Syndrome; Bronchopulmonary Dysplasia	Device: CPAP and room air	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 50 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Duration of Continuous Positive Airway Pressure and Pulmonary Function Testing in Preterm Infants
• Actual Study Start Date: Sep 1, 2014
• Actual Primary Completion Date: May 1, 2016
• Actual Study Completion Date: Sep 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: CPAP and room air Stable premature infants on CPAP and room air will be randomized to stay on CPAP for an additional two weeks.	Device: 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.; Other Names: continuous positive airway pressure
No Intervention: Room air Premature stable infants on CPAP and room air will be randomized to transition to room air alone.

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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.

2. 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.

3. 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 Outcome Measures

1. 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.

2. 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

3. 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.

4. 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.

5. 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.

6. 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.

7. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A to 1 Year
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Oregon Health & Science University	Portland	Oregon	United States	97239

Sponsors and Collaborators

• Oregon Health and Science University

Investigators

• Principal Investigator: Cindy T McEvoy, MD, MCR, Oregon Health and Science University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Cynthia McEvoy, Professor of Pediatrics, Oregon Health and Science University
• ClinicalTrials.gov Identifier: NCT02249143
• Other Study ID Numbers: eIRB00010607
• First Posted: Sep 25, 2014
• Last Update Posted: Aug 29, 2019
• Last Verified: Aug 1, 2019

• Keywords provided by Cynthia McEvoy, Professor of Pediatrics, Oregon Health and Science University: Continuous positive airway pressure; Prematurity; Respiratory distress syndrome; Bronchopulmonary dysplasia
• Additional relevant MeSH terms: Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Bronchopulmonary Dysplasia

Study Results

Participant Flow

Arm/Group Title	CPAP and Room Air	Room Air
Arm/Group Description	Stable premature infants on CPAP and room air will be randomized to stay on CPAP for an additional two weeks. 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.	Premature stable infants on CPAP and room air will be randomized to transition to room air alone.
Period Title: Overall Study
STARTED	24	26
COMPLETED	22	22
NOT COMPLETED	2	4

Baseline Characteristics

Arm/Group Title	Active Comparator: CPAP and Room Air	No Intervention: Room Air	Total
Arm/Group Description	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.	Premature stable infants on CPAP and room air will be randomized to transition to room air alone.	Total of all reporting groups
Overall Participants	22	22	44
Age (Count of Participants)
<=18 years	22 100%	22 100%	44 100%
Between 18 and 65 years	0 0%	0 0%	0 0%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	13 59.1%	8 36.4%	21 47.7%
Male	9 40.9%	14 63.6%	23 52.3%
Region of Enrollment (Count of Participants)
United States	22 100%	22 100%	44 100%

Outcome Measures

1. Primary Outcome

Title	Changes in the Measurements of Functional Residual Capacity (FRC) in Randomized Premature Infants
Description	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).

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	CPAP and Room Air	Room Air
Arm/Group Description	Stable premature infants on CPAP and room air will be randomized to stay on CPAP for an additional two weeks. 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.	Premature stable infants on CPAP and room air will be randomized to transition to room air alone.
Measure Participants	22	22
FRC change from baseline to two weeks	12.6 (11.4)	6.4 (10.1)
FRC change from baseline to discharge	27.2 (12.5)	17.1 (11.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CPAP and Room Air, Room Air
	Comments	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.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	6.62
	Confidence Interval	(2-Sided) 95%; 0.02 to 13.22
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Measurements of Passive Respiratory Compliance in Randomized Premature Infants
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	CPAP and Room Air	Room Air
Arm/Group Description	Stable premature infants on CPAP and room air will be randomized to stay on CPAP for an additional two weeks. 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.	Premature stable infants on CPAP and room air will be randomized to transition to room air alone.
Measure Participants	22	22
At Randomization	1.37 (0.28)	1.32 (0.28)
At End of 2 Weeks of Treatment	1.28 (0.28)	1.17 (0.18)
At Discharge	1.08 (0.18)	1.12 (0.21)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CPAP and Room Air, Room Air
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	>0.05
	Comments
	Method	t-test, 2 sided
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	CPAP and Room Air, Room Air
	Comments	Group differences in the secondary outcomes were tested at randomization, two weeks, and discharge using independent samples t-tests.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

3. Secondary Outcome

Title	Passive Respiratory Resistance in Randomized Premature Infants
Description	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.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	CPAP and Room Air	Room Air
Arm/Group Description	Stable premature infants on CPAP and room air will be randomized to stay on CPAP for an additional two weeks. 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.	Premature stable infants on CPAP and room air will be randomized to transition to room air alone.
Measure Participants	22	22
At Randomization	0.054 (0.014)	0.053 (0.009)
At End of 2 Weeks of Treatment	0.061 (0.014)	0.074 (0.021)
At Discharge	0.073 (0.02)	0.082 (0.022)

4. Secondary Outcome

Title	Measurements of Tidal Flow Volume Loops Will be Done in the Randomized Premature Infants.
Description	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.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	CPAP and Room Air	Room Air
Arm/Group Description	Stable premature infants on CPAP and room air will be randomized to stay on CPAP for an additional two weeks. 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.	Premature stable infants on CPAP and room air will be randomized to transition to room air alone.
Measure Participants	22	22
At Randomization	7.1 (1.1)	7.8 (0.97)
At End of 2 Weeks of Treatment	7.6 (1.1)	7.4 (0.9)
At Discharge	7.3 (1.1)	7.3 (0.56)

5. Other Pre-specified Outcome

Title	Changes in the Growth Parameters Between the Randomized Premature Infants
Description	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.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	CPAP and Room Air	Room Air
Arm/Group Description	Stable premature infants on CPAP and room air will be randomized to stay on CPAP for an additional two weeks. 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.	Premature stable infants on CPAP and room air will be randomized to transition to room air alone.
Measure Participants	22	22
At Randomization	1567 (293)	1482 (323)
At Discharge	2282 (354)	2253 (413)

6. Other Pre-specified Outcome

Title	The Number of Participants With Adverse Events and Serious Adverse Events in the Randomized Groups of Premature Infants.
Description	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).

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	CPAP and Room Air	Room Air
Arm/Group Description	Stable premature infants on CPAP and room air will be randomized to stay on CPAP for an additional two weeks. 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.	Premature stable infants on CPAP and room air will be randomized to transition to room air alone.
Measure Participants	22	22
Number [participants]	0 0%	0 0%

7. Other Pre-specified Outcome

Title	Corrected Gestational Age at Which Full Nipple Feeds Are Achieved
Description	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.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	CPAP and Room Air	Room Air
Arm/Group Description	Stable premature infants on CPAP and room air will be randomized to stay on CPAP for an additional two weeks. 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.	Premature stable infants on CPAP and room air will be randomized to transition to room air alone.
Measure Participants	22	22
Median (Inter-Quartile Range) [weeks]	35.9	35.5

8. Other Pre-specified Outcome

Title	Incidence of Wheezing Through One Year of Age
Description	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

Outcome Measure Data

Analysis Population Description

Number of participants analyzed is lower here as we were not able to follow all infants through 1 year of corrected age.

Arm/Group Title	CPAP and Room Air	Room Air
Arm/Group Description	Stable premature infants on CPAP and room air will be randomized to stay on CPAP for an additional two weeks. 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.	Premature stable infants on CPAP and room air will be randomized to transition to room air alone.
Measure Participants	18	21
Count of Participants [Participants]	7 31.8%	6 27.3%

9. Other Pre-specified Outcome

Title	Cost Comparison Between Randomized Groups
Description	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

Outcome Measure Data

Analysis Population Description

Data not collected

Arm/Group Title	CPAP and Room Air	Room Air
Arm/Group Description	Stable premature infants on CPAP and room air will be randomized to stay on CPAP for an additional two weeks. 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.	Premature stable infants on CPAP and room air will be randomized to transition to room air alone.
Measure Participants	0	0

10. Other Pre-specified Outcome

Title	Days on Oxygen Between the Randomized Groups
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	CPAP and Room Air	Room Air
Arm/Group Description	Stable premature infants on CPAP and room air will be randomized to stay on CPAP for an additional two weeks. 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.	Premature stable infants on CPAP and room air will be randomized to transition to room air alone.
Measure Participants	22	22
Mean (Inter-Quartile Range) [days]	0	0

11. Other Pre-specified Outcome

Title	Days in the Hospital
Description	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

Outcome Measure Data

Analysis Population Description

Data not collected

Arm/Group Title	CPAP and Room Air	Room Air
Arm/Group Description	Stable premature infants on CPAP and room air will be randomized to stay on CPAP for an additional two weeks. 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.	Premature stable infants on CPAP and room air will be randomized to transition to room air alone.
Measure Participants	0	0

Adverse Events

Arm/Group Title	CPAP and Room Air		Room Air
Arm/Group Description	Stable premature infants on CPAP and room air will be randomized to stay on CPAP for an additional two weeks. 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.		Premature stable infants on CPAP and room air will be randomized to transition to room air alone.
All Cause Mortality
	CPAP and Room Air		Room Air
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/24 (0%)		0/26 (0%)
Serious Adverse Events
	CPAP and Room Air		Room Air
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/24 (0%)		0/26 (0%)
Other (Not Including Serious) Adverse Events
	CPAP and Room Air		Room Air
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/24 (0%)		0/26 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.