CPAP Or Nasal Cannula Oxygen for Preterm Infants: A Randomized Controlled Trial (COCO)

The purpose of this study is to determine if in preterm infants < 34 weeks' gestation at birth receiving respiratory support with continuous positive airway pressure (CPAP) or nasal cannula (NC), CPAP compared with NC will decrease the number of episodes with oxygen saturations less than 85% of ≥10 seconds in a 24-hour randomized controlled trial. This will be a randomized controlled trial with a 1:1 parallel allocation of infants to CPAP or NC oxygen using stratified permuted block design.

Study Overview

• Status: Completed
• Conditions: Hypoxia; Respiratory Distress Syndrome; Bronchopulmonary Dysplasia; Infant, Newborn, Disease
• Intervention / Treatment: Procedure: Continuous positive airway pressure; Procedure: Nasal Cannula

Detailed Description

We hope to determine whether in preterm infants < 34 weeks' gestation at birth receiving respiratory support with continuous positive airway pressure (CPAP) or nasal cannula (NC), CPAP compared with NC will decrease the number of episodes with oxygen saturations less than 85% of ≥10 seconds in a 24-hour randomized controlled trial.

This study will include preterm infants < 34 weeks' gestation on respiratory support via CPAP with a PEEP ≤ 5 and FiO2 ≤ 30%. There will be two randomization strata [≥ 22+0/7 to ≤ 27+0/7 weeks, and ≥ 27+1/7 to ≤ 33+6/7 weeks. The purpose of stratification is to ensure an appropriate distribution of risk between study arms. This study will not be powered to detect outcome differences within or between strata.

Following informed consent, randomization, stratified by gestational age at delivery, will be performed using sequentially numbered sealed opaque envelopes. Each envelope will indicate either Treatment group (CPAP group) or Control group (NC group). The envelope will only be opened after informed consent has been obtained and just before starting the study on each infant.

This will be a single center randomized controlled trial with a 1:1 parallel allocation of infants to CPAP or NC oxygen using stratified permuted block design. 15-30 minutes will be provided as a washout period at the beginning of the intervention, followed by 24 hours on the intervention. Infants enrolled must meet CPAP stability criteria that are based on prior randomized clinical trials of weaning from CPAP to NC.

All infants enrolled in the study will have routine monitoring, uniform target saturation ranges of 91-95% with alarm limits set at 88-95%, and standard care for the duration of the study. The high alarm limit will be increased to 100% if an infant is weaned to 21% FiO2. Supplemental FiO2 will be titrated per unit routine to achieve goal target saturations. Pulse oximetry recordings will be downloaded using ixTrend (iexcellence, Wildau, Germany) software to a secure computer system or via Bedmaster software for later data analysis. The target oxygen saturations (91 to 95%) are based on data from the meta-analysis of randomized controlled trials of oxygen saturation targets which included data on 4911 infants from the SUPPORT, COT, and BOOST II trials.

Primary and secondary outcomes are described below. Other safety outcomes include recordings of episodes of bradycardia and circumstances surrounding the event. Pulse oximetry recordings will be downloaded using ixTrend software to a secure computer system for later data analysis. Abdominal and cerebral NIRS will also be performed with subsequent data analysis..

• Study Type: Interventional
• Enrollment (Actual): 38
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • UAB Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Infants must be currently utilizing CPAP (without a rate) with a PEEP ≤ 5 and FiO2 ≤ 30%
• Infants must meet CPAP stability criteria as follow:
• 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)
• Gestational age < 34 weeks' gestation at birth
• Informed consent by parents/legal guardians

Exclusion Criteria:

• presence of a major malformation
• a neuromuscular condition that affects respiration
• a terminal illness or decision to withhold or limit support
• currently being treated for sepsis
• enrollment in a competing trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• 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; Continuous positive airway pressure (CPAP) with blended oxygen delivered by binasal prongs or nasal mask.	Procedure: Continuous positive airway pressure; After study entry, CPAP will be provided via mask or binasal prongs in order to have a relatively uniform CPAP delivery system among infants in the treatment group. Bubble CPAP will be preferred over other modes of CPAP delivery. A PEEP of 5 will be used for uniformity.; Other Names: CPAP
Active Comparator: Nasal Cannula; Blended oxygen delivered by nasal cannula (NC).	Procedure: Nasal Cannula; After study entry, flow will be set to 0.5 L/kg with 1L maximum while on NC during the study period to reduce the risk of inadvertent PEEP with higher flows. Initial FiO2 can be titrated to achieve target saturations, and may be increased up to 100% while on NC.; Other Names: NC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The number of episodes with oxygen saturations less than 85% for ≥ 10 seconds	24 hours of intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The coefficient of variability of oxygen saturations (relative standard deviation)	The coefficient of variation is a standardized measure of dispersion of a frequency distribution defined as the ratio of the standard deviation to the mean. It will be used in this study to assess the stability of oxygen saturations.	24 hours of intervention
The proportion of time with oxygen saturations > 95 % among infants requiring supplemental oxygen		24 hours of intervention
The proportion of time spent outside oxygen saturation target ranges (91-95%) among infants requiring supplemental oxygen		24 hours of intervention
The proportion of time with oxygen saturations less than 85%		24 hours of intervention
The median supplemental oxygen concentration		24 hours of intervention
The median transcutaneous carbon dioxide value		24 hours of intervention
The number of episodes (≥ 10 seconds) with oxygen saturations less than 80 %		24 hours of intervention
The number of recorded episodes (≥ 10 seconds) of bradycardia < 100/min		24 hours of intervention
The median cNIRS value	Median cerebral near-infrared spectroscopy value during the 24 hour intervention period	24 hours of intervention
The median aNIRS value	Median abdominal near-infrared spectroscopy value during the 24 hour intervention period	24 hours of intervention

Collaborators and Investigators

• Sponsor: University of Alabama at Birmingham
• Investigators: Study Director: Waldemar A Carlo, MD, University of Alabama at Birmingham

Study record dates

Study Major Dates

• Study Start (Actual): August 16, 2021
• Primary Completion (Actual): March 29, 2023
• Study Completion (Actual): March 29, 2023

Study Registration Dates

• First Submitted: March 5, 2021
• First Submitted That Met QC Criteria: March 8, 2021
• First Posted (Actual): March 10, 2021

Study Record Updates

• Last Update Posted (Actual): January 26, 2024
• Last Update Submitted That Met QC Criteria: January 24, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Signs and Symptoms, Respiratory; Lung Injury; Infant, Premature, Diseases; Ventilator-Induced Lung Injury; Hypoxia; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Bronchopulmonary Dysplasia; Infant, Newborn, Diseases
• Other Study ID Numbers: UAB Neo ZY 2021

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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