Structured CPAP Weaning for Neonatal Respiratory Failure

(Flow&Grow Trial)

Recruiting at 3 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

Trial Summary

What is the purpose of this trial?

Preterm neonates born at less than 30 weeks' gestation are commonly maintained on invasive or non-invasive respiratory support to facilitate gas exchange. While non-invasive respiratory support (NIS) can be gradually reduced over time as the infant grows, most weaning strategies often lead to weaning failure. This failure is evidenced by an increase in significant events such as apneas, desaturations, and/or bradycardias, increased work of breathing, or an inability to oxygenate or ventilate, resulting in escalated respiratory support. Although the optimal approach to weaning NIS remains uncertain, neonatal units that delay Continuous Positive Airway Pressure (CPAP) weaning until 32-34 weeks corrected gestational age exhibit lower rates of chronic lung disease. Therefore, the investigators aim to compare the duration on respiratory support and oxygen exposure in infants born at less than 30 weeks' gestational age who undergo a structured weaning protocol that includes remaining on CPAP until at least 32-34 weeks corrected gestational age (CGA). The hypothesis posits that preterm infants following a structured weaning protocol, including maintaining CPAP until a specific gestational age, will demonstrate lower rates of weaning failure off CPAP (defined as requiring more support and/or experiencing increased stimulation events 72 hours after CPAP weaning) than those managed according to the medical team's discretion.

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 data supports the effectiveness of the treatment Structured CPAP Weaning for Neonatal Respiratory Failure?

Research shows that using a structured approach to wean premature infants from CPAP (a breathing support machine) is feasible, but there were no significant differences in short-term breathing outcomes compared to non-standardized methods. More research is needed to determine the best weaning strategy. ^{1 2 3 4 5}

Is structured CPAP weaning safe for humans?

The research articles focus on methods for weaning preterm infants from CPAP, but they do not provide specific safety data. However, CPAP is widely used in preterm infants, suggesting it is generally considered safe in this population. ^{2 4 6 7 8}

How is the Structured CPAP Weaning treatment different from other treatments for neonatal respiratory failure?

The Structured CPAP Weaning treatment is unique because it uses a standardized protocol to gradually reduce the use of continuous positive airway pressure (CPAP) in infants, unlike other methods that may not follow a specific plan. This approach aims to provide a more consistent and potentially more effective way to help infants transition off CPAP support. ^{1 4 7 8 9}

Research Team

Sandra Leibel, MD

Principal Investigator

University of California, San Diego

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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 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 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]

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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Standardized weaning of infants [2019]

2. Singapore 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. [2019]

3. Iran pubmed.ncbi.nlm.nih.gov

High flow nasal cannula as a method for rapid weaning from nasal continuous positive airway pressure. [2020]

4. United States pubmed.ncbi.nlm.nih.gov

Comparison of sprinting vs non-sprinting to wean nasal continuous positive airway pressure off in very preterm infants. [2019]

5. England pubmed.ncbi.nlm.nih.gov

Randomised controlled trial of weaning strategies for preterm infants on nasal continuous positive airway pressure. [2018]

6. United States pubmed.ncbi.nlm.nih.gov

Oxygen saturation histograms predict nasal continuous positive airway pressure-weaning success in preterm infants. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

Implementation of a protocol-based strategy for weaning nasal high flow therapy in preterm infants. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

Gradual versus sudden weaning from nasal CPAP in preterm infants: a pilot randomized controlled trial. [2013]

9. Poland pubmed.ncbi.nlm.nih.gov

[Weaning newborns from noninvasive ventilation]. [2014]