Continued Pressure for Alveolar Protection (CPAP Trial) (CPAP)

Continued Pressure for Alveolar Protection: A Randomized Controlled Trial (CPAP Trial)

The objective of the CPAP Trial is to test whether extending CPAP until 34 weeks' PMA or for at least 2 additional weeks compared to weaning to a nasal canula will decrease the likelihood of bronchopulmonary dysplasia or death at 36 weeks' PMA.

Study Overview

• Status: Not yet recruiting
• Conditions: Bronchopulmonary Dysplasia (BPD)
• Intervention / Treatment: Device: CPAP; Device: Nasal Cannula

• Study Type: Interventional
• Enrollment (Estimated): 860
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Gestational age <29 weeks at birth
• PMA <32 weeks at study entry
• On treatment with CPAP without a rate in FiO2 <0.25 and PEEP of 4-5 cmH2O
• Meet stability criteria:
• If previously intubated must be extubated ≥ 72 hours
• <3 self-resolving apneas (≤ 20 s) and/or bradycardia (<100 bpm) in any hour over previous 6 hours
• No episodes of apnea or bradycardia requiring intervention (oxygen/stimulation/bag and mask) for 24 hours
• Parents/legal guardians consent for enrollment

Exclusion Criteria:

• Major malformation
• Neuromuscular condition that affects respiration
• Terminal illness
• Decision to withhold or limit support
• Too sick to participate in opinion of Attending physician
• Clinical shock, sepsis
• Planned surgery during study period

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Continuous Positive Airway Pressure; CPAP will be provided via mask or binasal prongs to maintain a relatively uniform CPAP delivery system among infants in the treatment group. Bubble CPAP will be preferred over other modes of CPAP delivery whenever available.	Device: CPAP; Prior to study entry, the CPAP interface (includes RAM cannula, Optiflow, large bore cannulas, mask, prongs) and mode (bubble, variable-flow, ventilator-derived) used is at the discretion of the provider and center. After study entry, CPAP will be provided via mask or binasal prongs to maintain a relatively uniform CPAP delivery system among infants in the treatment group. Bubble CPAP will be preferred over other modes of CPAP delivery whenever available.
Active Comparator: Nasal Cannula; HFNC at 4 L/min will be used initially in the control group. Flow should be titrated down by 1 L/min per day until ≤0.5 L/kg among infants in the nasal cannula group if not meeting pre-specified failure criteria to reduce the risk of inadvertent positive end-expiratory pressure (PEEP). Flow can also be increased (up to 6 L/min maximum) if needed among infants on NC who meet the pre-specified failure criteria. Infants in the control group placed back on CPAP may use an interface at provider discretion.	Device: Nasal Cannula; HFNC at 4 L/min will be used initially in the control group. Flow should be titrated down by 1 L/min per day until ≤0.5 L/kg among infants in the nasal cannula group if not meeting pre-specified failure criteria to reduce the risk of inadvertent positive end-expiratory pressure (PEEP). Flow can also be increased (up to 6 L/min maximum) if needed among infants on NC who meet the pre-specified failure criteria. Infants in the control group placed back on CPAP may use an interface at provider discretion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bronchopulmonary Dysplasia or Death	The likelihood of BPD or death at 36 weeks' Postmenstrual Age (PMA): a five-level ordinal outcome (death, survival with grade 3 BPD, survival with grade 2 BPD, survival with grade 1 BPD, and survival free of any BPD).	36 Weeks' PMA

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Days alive and off respiratory support	The number of days alive and off respiratory support from 34 weeks' to 40 weeks' PMA	34-40 weeks' PMA
Mortality at 36 Weeks	Mortality	36 Weeks' PMA
Death or Grade 2-3 BPD	Mortality at 36 weeks' PMA or grade 3 BPD	36 Weeks' PMA
Death or Grade 3 BPD	Mortality or grade 3 BPD	36 Weeks' PMA
Retinopathy of prematurity	Retinopathy of prematurity ≥ stage 3 or requiring treatment (laser/anti-VEGF)	52 weeks' PMA
Respiratory support, supplemental oxygen, and pulmonary medications	Use of supplemental oxygen, respiratory support (including low-flow nasal cannula), and pulmonary medications (methylxanthines, steroids, diuretics, albuterol) at discharge and 40 weeks' PMA	40 weeks' PMA
Full PO feedings	PMA at first full PO feeding (where full PO feeding is defined as intake of 120 mL/kg/day by mouth, even if an NG tube remains in situ)	52 weeks' PMA
Length of hospitalization	Length of hospitalization from 34 weeks' PMA	52 Weeks' PMA

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Post-prematurity respiratory disease at two years follow up	Post-prematurity respiratory disease (PPRD) or death at 22-26 months follow-up.	22-26 months
Pulmonary medications and respiratory support at two years follow up	Pulmonary medications (inhaled or oral steroids, bronchodilators, diuretics, and vasodilators), history of rehospitalizations for respiratory reasons, pulmonary clinic visits, respiratory support (including oxygen, CPAP, or ventilation), bronchoscopy, and respiratory-related surgeries such as tracheal surgeries, repairs, and dilatations; and wheezing or diagnosis of asthma using a modified ISAAC questionnaire at 22-26 months follow-up.	22-26 months
Long-term mortality	Mortality at 22-28 month follow up	22-26 months
Nasal/skin injury	Presence of nasal/skin injury during study intervention period	36 Weeks' PMA
Nebulized epinephrine to treat Stridor	Nebulized epinephrine for stridor during intervention period	36 Weeks' PMA
Tracheomalacia	Tracheomalacia diagnosed by bronchoscopy before discharge	52 Weeks' PMA
Intubation, chest compressions/epinephrine	Intubation and/or chest compressions/epinephrine during study intervention period	36 Weeks' PMA
Pneumothorax	Pneumothorax during study intervention period	36 Weeks' PMA

Collaborators and Investigators

• Sponsor: NICHD Neonatal Research Network
• Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Study record dates

Study Major Dates

• Study Start (Estimated): November 5, 2026
• Primary Completion (Estimated): November 5, 2028
• Study Completion (Estimated): January 30, 2029

Study Registration Dates

• First Submitted: January 16, 2026
• First Submitted That Met QC Criteria: February 10, 2026
• First Posted (Actual): February 18, 2026

Study Record Updates

• Last Update Posted (Actual): June 2, 2026
• Last Update Submitted That Met QC Criteria: June 1, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Continuous Positive Airway Pressure; CPAP
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Infant, Premature, Diseases; Infant, Newborn, Diseases; Lung Injury; Ventilator-Induced Lung Injury; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Bronchopulmonary Dysplasia; Equipment and Supplies; Catheters; Cannula
• Other Study ID Numbers: NICHD-NRN-0067; 1U01HD115553-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: NIH has had a long-standing policy to share and make available to the public the results and accomplishments of the activities that it funds. The NRN plans to share de-identified data after final publication in an NIH supported data repository such as the NICHD Data and Specimen Hub (https://dash.nichd.nih.gov).

Drug and device information, study documents

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