Structured CPAP Weaning for Neonatal Respiratory Failure

(Flow&Grow Trial)

Recruiting at 4 trial locations

Overseen By Sarah Lazar, MPH

Age: < 18

Sex: Any

Trial Phase: Academic

Sponsor: University of California, San Diego

Disqualifiers: Congenital anomalies, NEC, SIP, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 9-11 weeks

130 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method to help very premature babies (born before 30 weeks) breathe better. It compares two approaches: a structured plan that maintains babies on breathing support (CPAP, or Continuous Positive Airway Pressure) until they reach 32-34 weeks, and the usual care determined by doctors. The researchers aim to determine if the structured plan enables babies to breathe independently more successfully and reduces the need for extra oxygen. Babies born before 30 weeks who are in the NICU and have no major health issues may be suitable for this trial. As an unphased trial, this study provides a unique opportunity to enhance understanding and improve care for very premature babies.

Do I have to stop my current medications for the trial?

The trial information does not specify whether participants need to stop taking their current medications.

What prior data suggests that this structured CPAP weaning protocol is safe for preterm neonates?

Research shows that Continuous Positive Airway Pressure (CPAP) often aids premature babies with breathing problems. Studies have found CPAP to be safe and effective in improving their breathing. For instance, one study tested a new method to gradually reduce CPAP use and found it both feasible and safe.

Another study discovered that switching from CPAP to another support method, such as nasal high flow (nHF), was as effective as stopping CPAP at a certain point. This indicates that CPAP and methods to reduce its use are generally well-tolerated by babies.

In summary, research supports the use of CPAP and planned reduction methods in premature infants, demonstrating safety and effectiveness in addressing breathing issues. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the structured CPAP weaning protocol for neonatal respiratory failure because it offers a more standardized approach to transitioning infants off respiratory support. Unlike current methods, which vary widely based on individual unit practices, this protocol uses clear algorithms and criteria to help healthcare professionals make more consistent and informed decisions. This could potentially lead to more predictable outcomes, reduce the likelihood of weaning failure, and improve overall care for newborns with respiratory challenges. By implementing stability and failure criteria, the protocol aims to tailor weaning to each infant's needs, potentially reducing the duration of respiratory support and the associated risks.

What evidence suggests that this structured CPAP weaning protocol is effective for neonatal respiratory failure?

Research shows that removing preterm infants from CPAP (a type of breathing support) too early, particularly before 32 weeks of corrected gestational age, results in a 76% chance of needing breathing assistance again. This trial will compare two approaches: a control group where infants are weaned based on unit-specific practices, and a treatment group following a structured CPAP weaning protocol. Studies have found that a structured plan, which includes keeping infants on CPAP until they reach at least 32-34 weeks, leads to better outcomes. These outcomes include fewer breathing problems like pauses in breathing, reduced need for additional breathing support, and a lower risk of developing long-term lung issues. Clear guidelines for when and how to reduce breathing support seem to help these tiny patients breathe better as they grow. ^{2 4 5 6 7}

Who Is on the Research Team?

Sandra Leibel, MD

Principal Investigator

University of California, San Diego

Are You a Good Fit for This Trial?

This trial is for preterm infants born at less than 30 weeks' gestational age who are in the NICU and have not been intubated for over 4 weeks. Infants with long-term support needs due to conditions like pulmonary hypoplasia or genetic syndromes cannot participate.

Inclusion Criteria

Informed parental consent obtained

Babies born at less than 30 weeks of pregnancy and admitted to specific hospitals' neonatal intensive care units.

Exclusion Criteria

Declined or unable to give informed consent

I have been on a breathing machine for more than 4 weeks.

My infant has a long-term health condition needing support, like breathing issues or genetic syndromes.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Infants receive non-invasive respiratory support (NIS) with a structured weaning protocol until 32-34 weeks corrected gestational age (CGA), depending on gestational age at birth.

9-11 weeks

Weaning

Infants are weaned off CPAP/NIS following a standardized protocol or unit-specific practices.

72 hours

Follow-up

Participants are monitored for safety and effectiveness after weaning off CPAP/NIS.

4 months

What Are the Treatments Tested in This Trial?

Interventions

• Standardized/structured CPAP weaning protocol

Trial Overview

The study tests a structured weaning protocol from CPAP, hypothesizing that maintaining it until at least 32-34 weeks corrected gestational age will reduce weaning failure compared to standard care.

How Is the Trial Designed?

Group I: Standardized NIS Wean Experimental Treatment 1 Intervention

A standardized maintenance/weaning protocol will be implemented for the treatment group (standardized NIS wean). All infants in the treatment group will remain on NIS until either 32 or 34 weeks CGA, depending on their gestational age at birth. Infants born at 27 6/7 weeks or less will continue on NIS until at least 34 weeks if they are in the treatment group, whereas infants born between 28 0/7 and 29 6/7 weeks will stay on NIS until at least 32 weeks if they are in the treatment group. The weaning protocol in the treatment group will incorporate algorithms outlining stability criteria, failure criteria, and algorithms for registered nurses (RNs) and respiratory therapists (RTs), including steps to take in such situations. The control group will be weaned according to the unit's or medical team's practices.

Group II: Control Active Control 1 Intervention

Babies in the control group (non-standardized wean) will be weaned based on unit specific practices.

Standardized/structured CPAP weaning protocol is already approved in United States for the following indications:

Approved in United States as Standardized CPAP weaning protocol for:

• Prevention of chronic lung disease in preterm infants
• Reduction of weaning failure in preterm infants

Who Is Running the Clinical Trial?

University of California, San Diego

Lead Sponsor

Trials

1,215

Recruited

1,593,000+

Rady Children's Hospital, San Diego

Collaborator

Trials

42

Recruited

14,300+

Published Research Related to This Trial

In a study of 36 preterm infants receiving CPAP, those who successfully transitioned off CPAP had significantly higher oxygen saturation levels prior to weaning compared to those who were placed back on CPAP.

Infants who maintained oxygen saturations of 95-100% for longer durations were more likely to remain off CPAP for at least 7 days, indicating that monitoring oxygen levels can help identify readiness for weaning from CPAP.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oxygen saturation histograms predict nasal continuous positive airway pressure-weaning success in preterm infants. Gentle, SJ., Ambalavanan, N., Carlo, WA.[2021]

The study aims to provide specific recommendations for weaning infants off nasal continuous positive airway pressure (nCPAP) and nasal intermittent positive pressure ventilation (NIPPV), which are commonly used for treating respiratory insufficiency in infants.

These recommendations are based on existing data and a comprehensive survey of Polish neonatologists and pediatric intensive care specialists, addressing a gap in the current clinical guidelines for weaning from these respiratory support methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Weaning newborns from noninvasive ventilation]. Bober, K., Swietliński, J., Musialik-Swietlińska, E., et al.[2014]

A standardized approach to weaning premature infants from continuous positive airway pressure (CPAP) was found to be feasible in a study comparing 41 infants post-intervention to 36 pre-intervention infants.

However, the study did not show significant differences in short-term respiratory outcomes between the two groups, indicating that more extensive clinical trials are needed to establish effective weaning protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Standardized weaning of infants Kidszun, A., Plate, M., Arnold, C., et al.[2019]

In a study of 88 stable preterm infants, weaning from nasal continuous positive airway pressure (NCPAP) to high flow nasal cannula (HFNC) significantly reduced the duration of oxygen therapy (20.6 hours vs. 49.6 hours) and length of hospital stay (11.3 days vs. 14.8 days).

Both weaning methods showed similar rates of successful weaning, indicating that while HFNC may offer logistical benefits, it does not compromise the effectiveness of transitioning off respiratory support.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High flow nasal cannula as a method for rapid weaning from nasal continuous positive airway pressure. Badiee, Z., Eshghi, A., Mohammadizadeh, M.[2020]

In a study involving 86 infants born before 31 weeks gestational age, both sprinting (gradually increasing spontaneous breathing time) and non-sprinting (weaning pressure down) protocols for weaning from nasal continuous positive airway pressure (NCPAP) were found to be equally effective, with similar success rates of 77% and 75%, respectively.

There were no significant differences in the occurrence of common neonatal complications, such as bronchopulmonary dysplasia or severe retinopathy of prematurity, between the two weaning methods, suggesting that either approach is safe for premature infants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of sprinting vs non-sprinting to wean nasal continuous positive airway pressure off in very preterm infants. Eze, N., Murphy, D., Dhar, V., et al.[2019]

In a study of 181 very low birth weight preterm infants, using low oxygen flow for weaning from nasal continuous positive airway pressure (NCPAP) significantly reduced the time needed to wean off respiratory support to 11.6 days compared to 16.0 days for CPAP and 15.0 days for air flow methods.

However, the low oxygen flow method was associated with a higher incidence of retinopathy of prematurity (ROP) and bronchopulmonary dysplasia (BPD), suggesting that while it may speed up weaning, it also increases risks related to oxygen toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized pilot study comparing the role of PEEP, O2 flow, and high-flow air for weaning of ventilatory support in very low birth weight infants. Yang, CY., Yang, MC., Chu, SM., et al.[2019]

In a study of 56 preterm infants born at or before 32 weeks, both sudden and gradual methods of weaning from nasal CPAP (NCPAP) showed no significant difference in success rates, indicating that either method can be effective.

The timing of successful weaning and the infants' weight at that time were also similar between the two groups, suggesting that factors like pulmonary maturity may play a more critical role in the weaning process than the method used.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gradual versus sudden weaning from nasal CPAP in preterm infants: a pilot randomized controlled trial. Rastogi, S., Wong, W., Gupta, A., et al.[2013]

In a study of 60 very preterm infants, the abrupt weaning from NCPAP using high flow nasal cannula (HFNC) significantly reduced the duration of NCPAP to just 1 day compared to 24 days in other groups, indicating a potential benefit of this approach.

However, while HFNC may assist in weaning, it did not lead to a reduction in overall respiratory support duration or time to full suck feeds, and the abrupt wean without HFNC resulted in a higher rate of parental withdrawal from the study.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomised controlled trial of weaning strategies for preterm infants on nasal continuous positive airway pressure. Tang, J., Reid, S., Lutz, T., et al.[2018]

A standardized protocol for weaning preterm infants from nasal high flow therapy (nHFT) significantly reduced the failure rate of weaning, with only 7.8% of infants failing compared to 28.3% in the nonprotocolized group.

The protocol group also achieved full enteral feeding faster than the nonprotocol group, indicating that a structured approach to weaning can improve feeding outcomes without increasing risks of respiratory support or neonatal complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Implementation of a protocol-based strategy for weaning nasal high flow therapy in preterm infants. Abobakr, M., Abdalla, A., Barakat, T., et al.[2021]

Citations

1.

clinicaltrials.ucsd.edu

clinicaltrials.ucsd.edu/trial/NCT06123143

The Ideal Time to Wean CPAP Off In Extremely Low Birth ...

For infants > 28 weeks, the retrospective review demonstrated a 76% failure rate if weaned off CPAP before 32 weeks, while those who remained on ...

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC9763181/

A randomised trial comparing weaning from CPAP alone with ...

This trial shows that - when using strict weaning and failure criteria - weaning from nCPAP using nasal high flow was non-inferior to weaning from nCPAP alone.

3.

researchgate.net

researchgate.net/publication/283720546_Standardized_weaning_of_infants_32_weeks_of_gestation_from_Continuous_Positive_Airway_Pressure_-_a_feasibility_study

Standardized weaning of infants <32 weeks of gestation ...

Standardized weaning was feasible but no significant differences in short term respiratory outcomes were observed. Weaning from CPAP was ...

4.

bmcpediatr.biomedcentral.com

bmcpediatr.biomedcentral.com/articles/10.1186/s12887-024-05167-2

Feasibility and safety of weaning premature infants from nasal ...

This study evaluated the feasibility and safety of a newly designed protocol for NCPAP weaning with cyclic HFNC use for premature infants.

5.

nature.com

nature.com/articles/s41372-021-01200-9

A comparison of methods of discontinuing nasal CPAP in ...

The objective of this study was to determine whether abrupt discontinuation vs gradual wean of nasal CPAP (NCPAP) in infants <30 weeks gestation results in a ...

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC8094155/

Continuous positive airway pressure (CPAP) for respiratory ...

CPAP has been used for the prevention and treatment of respiratory distress, as well as for the prevention of apnoea, and in weaning from IPPV.

7.

fn.bmj.com

fn.bmj.com/content/108/1/63

A randomised trial comparing weaning from CPAP alone with ...

For infants ready to wean from nCPAP, the CHiPS study found that nHF was non-inferior to discontinuing nCPAP at 5 cm water.