Extending CPAP Therapy in Stable Preterm Infants to Increase Lung Growth and Function

Extending CPAP Therapy in Stable Preterm Infants to Increase Lung Growth and Function: A Randomized Controlled Trial

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.

Study Overview

• Status: Completed
• Conditions: Premature Birth; Respiratory Distress Syndrome; Neonatal
• Intervention / Treatment: Other: Additional 2 weeks of CPAP

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.

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Oregon
    • Portland, Oregon, United States, 97239
      • Doernbecher Neonatal Care Center at Oregon Health & Science University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 day to 2 months (Child)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: eCPAP; Participants will remain on CPAP for 2 additional weeks once CPAP stability criteria is met.	Other: Additional 2 weeks of CPAP; Subjects will be randomized to an additional 2 weeks of CPAP vs. discontinuing CPAP per usual care.
No Intervention: dCPAP; Participants will discontinue CPAP as per usual care once CPAP stability criteria is met.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	4 - 8 months of age

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	4 - 8 months of age
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.	4 - 8 months of age

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	through 12 months of age (+/- 2 months)
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.	through 12 months of age (+/- 2 months)

Collaborators and Investigators

• Sponsor: Cynthia McEvoy
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI); Indiana University
• Investigators: Principal Investigator: Cindy McEvoy, MD, Oregon Health and Science University

Publications and helpful links

General Publications

• Lam R, Schilling D, Scottoline B, Platteau A, Niederhausen M, Lund KC, Schelonka RL, MacDonald KD, McEvoy CT. The Effect of Extended Continuous Positive Airway Pressure on Changes in Lung Volumes in Stable Premature Infants: A Randomized Controlled Trial. J Pediatr. 2020 Feb;217:66-72.e1. doi: 10.1016/j.jpeds.2019.07.074. Epub 2019 Sep 10.
• Praca ELL, Tiller CJ, Kisling JA, Tepper RS. An alternative method to measure the diffusing capacity of the lung for carbon monoxide in infants. Pediatr Pulmonol. 2018 Mar;53(3):332-336. doi: 10.1002/ppul.23926. Epub 2017 Dec 19.
• McEvoy CT, MacDonald KD, Go MA, Milner K, Harris J, Schilling D, Olson M, Tiller C, Slaven JE, Bjerregaard J, Vu A, Martin A, Mamidi R, Schelonka RL, Morris CD, Tepper RS. Extended Continuous Positive Airway Pressure in Preterm Infants Increases Lung Growth at 6 Months: A Randomized Controlled Trial. Am J Respir Crit Care Med. 2025 Apr;211(4):610-618. doi: 10.1164/rccm.202411-2169OC.

Study record dates

Study Major Dates

• Study Start (Actual): January 10, 2020
• Primary Completion (Actual): September 18, 2023
• Study Completion (Actual): March 15, 2024

Study Registration Dates

• First Submitted: December 31, 2019
• First Submitted That Met QC Criteria: March 2, 2020
• First Posted (Actual): March 4, 2020

Study Record Updates

• Last Update Posted (Actual): August 17, 2025
• Last Update Submitted That Met QC Criteria: July 30, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Respiratory Tract Diseases; Lung Diseases; Respiration Disorders; Infant, Premature, Diseases; Infant, Newborn, Diseases; Premature Birth; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn
• Other Study ID Numbers: eCPAP; R33HL147906 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Deidentified individual patient data related to primary outcome
• IPD Sharing Time Frame: One year after publication of primary paper, lasting for 5 years.
• IPD Sharing Access Criteria: Signed data access agreement
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No