CPAP vs NIPPV for Premature Infants

Age: < 18

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: Sunnybrook Health Sciences Centre

Must not be taking: Narcotic analgesics, Gastric motility agents

Disqualifiers: Congenital anomalies, Sepsis, NEC, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

Background: In premature babies, many organ systems are not fully grown and developed, including the lungs and respiratory muscles, so they will need breathing support to help them to breathe by preventing their tiny air sacs to collapse. This support commonly done by CPAP and Non-Invasive Positive Pressure Ventilation (NIPPV) therapy by giving some pressure and oxygen to their lungs through an interface placed on their noses. Both (CPAP and NIPPV) can be used as a support modality for respiratory distress syndrome, apnea of prematurity, and providing breathing support after extubation from the full mechanical breathing support. The CPAP supports the baby's immature lungs by delivering constant pressure to keep their lungs and breathing well supported. Whereas the NIPPV will use constant pressure in the background (similar to CPAP), and on top, it will give extra intermittent puffs at regular intervals to support the baby's breathing. The NIPPV is the most common choice by the clinicians when the traditional CPAP is no longer effective, to avoid the full mechanical breathing support and to protect the developing lungs. Studies suggested that NIPPV is better than the traditional CPAP in reducing the need of the baby to need full mechanical breathing support. This might be because the investigators tend to use lower pressures with CPAP (5-8 cmH2O) compared to relatively higher pressures with NIPPV. More recently, clinicians showed the safety of using equivalent higher CPAP pressures (\>9 cmH2O) to what the investigators use in the NIPPV in preterm babies. One way to measure the support that the investigators are giving to the patient with the different devices is to measure the diaphragm activity, which the investigators call the Edi signal, using a special feeding catheter and a specific machine to measure it. The catheter is placed and used as a routine feeding tube but has sensors at the end to measure this Edi signal. One opening of the tube will be connected to a computer to record the Edi signals. The other opening of the tube will be used for feeding.

Will I have to stop taking my current medications?

The trial does not specify if participants must stop taking their current medications, but it excludes infants on certain treatments like narcotic analgesics and gastric motility agents. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the treatment Edi Signal Measurement, Diaphragm Electrical Activity Measurement for premature infants?

The research suggests that measuring the electrical activity of the diaphragm (Edi) can help compare the effectiveness of different breathing support methods like CPAP and NIPPV in premature infants. This measurement may provide insights into how well these treatments support breathing in preterm babies. ^{1 2 3 4 5}

Is CPAP or NIPPV safe for premature infants?

Studies have shown that both CPAP and NIPPV are generally safe for premature infants, with some research indicating that NIPPV may be more effective in certain cases. Safety concerns like feed intolerance, necrotizing enterocolitis (a serious intestinal disease), and other conditions were monitored, but no significant safety issues were highlighted in the studies. ^{1 2 3 4 6}

How does Edi Signal Measurement differ from other treatments for premature infants?

Edi Signal Measurement is unique because it monitors the electrical activity of the diaphragm, helping to tailor respiratory support to the infant's natural breathing efforts, unlike CPAP or NIPPV which provide constant or intermittent pressure without this personalized adjustment. ^{1 2 3 4 7}

Research Team

Eligibility Criteria

This trial is for very low birth weight preterm infants who need breathing support due to immature lungs. It's not suitable for those with certain medical conditions that the study doesn't specify.

Inclusion Criteria

My baby was born weighing less than 1500 grams and is now stable.

My baby is in the NICU on mild breathing support and needs a little extra oxygen.

Exclusion Criteria

My infant has air trapped in the chest or around the lungs.

My infant is in the period right after surgery.

I have a brain condition from birth or developed one that includes severe bleeding or seizures.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants are assigned to different sequences of CPAP and NIPPV for 6 hours to measure diaphragm electrical activity (Edi)

6 hours

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1-2 weeks

Treatment Details

Interventions

• Edi Signal Measurement (Other)

Trial Overview The study tests how different non-invasive breathing supports affect diaphragm activity in premature babies. It compares traditional CPAP, NIPPV, and high-pressure CPAP to see which helps their tiny lungs best.

Participant Groups

Group I: Traditional CPAP, then high CPAP, then NIPPV Experimental Treatment 1 Intervention

The participant will stay for 2 hours on Traditional CPAP, then 2 hours on high CPAP, then 2 hours on NIPPV. The investigators will continue to record the Edi signals during the 3 methods.

Group II: Traditional CPAP, then NIPPV, then high CPAP. Experimental Treatment 1 Intervention

The participant will stay for 2 hours on Traditional CPAP, then 2 hours on NIPPV, then 2 hours on high CPAP. The investigators will continue to record the Edi signals during the 3 methods.

Group III: NIPPV, then traditional CPAP, then high CPAP Experimental Treatment 1 Intervention

The participant will stay for 2 hours on NIPPV, then 2 hours on traditional CPAP, then 2 hours on high CPAP. The investigators will continue to record the Edi signals during the 3 methods.

Group IV: NIPPV, then high CPAP, then traditional CPAP. Experimental Treatment 1 Intervention

The participant will stay for 2 hours on NIPPV, then 2 hours on high CPAP, then 2 hours on traditional CPAP. The investigators will continue to record the Edi signals during the 3 methods.

Group V: High CPAP, then traditional CPAP, then NIPPV. Experimental Treatment 1 Intervention

The participant will stay for 2 hours on High CPAP, then 2 hours on traditional CPAP, then 2 hours on NIPPV. The investigators will continue to record the Edi signals during the 3 methods.

Group VI: High CPAP, then NIPPV, then traditional CPAP. Experimental Treatment 1 Intervention

The participant will stay for 2 hours on High CPAP, then 2 hours on NIPPV, then 2 hours on traditional CPAP. The investigators will continue to record the Edi signals during the 3 methods.

Who Is Running the Clinical Trial?

Sunnybrook Health Sciences Centre

Lead Sponsor

Trials

693

Recruited

1,569,000+

Dr. Rajin Mehta

Sunnybrook Health Sciences Centre

Chief Medical Officer

MD from University of Toronto

Dr. Andrew J. Smith

Sunnybrook Health Sciences Centre

President and CEO since 2017

MD, MSc from University of Toronto; Surgical Oncology Fellowship at Memorial Sloan-Kettering Cancer Center

Findings from Research

In a study of 10 premature infants, the electrical activity of the diaphragm (Edi) was significantly lower when using noninvasive neurally adjusted ventilatory assist (NIV NAVA) compared to continuous positive airway pressure (CPAP), suggesting that NIV NAVA may provide less respiratory effort for these infants.

The use of NIV NAVA was found to be safe, with no major adverse events reported during the monitoring period, indicating its feasibility in a busy neonatal unit.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Electrical Activity of the Diaphragm in a Small Cohort of Preterm Infants on Noninvasive Neurally Adjusted Ventilatory Assist and Continuous Positive Airway Pressure: A Prospective Comparative Pilot Study. Gupta, A., Lumba, R., Bailey, S., et al.[2020]

In a study of 172 extremely preterm neonates (22-28 weeks' gestation), high continuous positive airway pressure (CPAP) and nasal intermittent positive pressure ventilation (NIPPV) showed no significant difference in failure rates within 7 days, indicating both methods are similarly effective.

Infants on high CPAP were more likely to require an alternate noninvasive support mode, suggesting that while both methods are effective, high CPAP may lead to a higher need for additional respiratory support.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of High CPAP versus NIPPV in Preterm Neonates: A Retrospective Cohort Study. Ahmad, HA., Deekonda, V., Patel, W., et al.[2023]

In a study of 216 neonates with respiratory distress, nonsynchronized nasal intermittent positive pressure ventilation (NIPPV) was found to be significantly more effective than continuous positive airway pressure (CPAP) in preventing the need for intubation within 72 hours of starting treatment.

NIPPV also showed advantages in reducing the duration of noninvasive ventilation, the occurrence of bronchopulmonary dysplasia (BPD), and the length of hospital stay, suggesting it may be a better primary respiratory support option for newborns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nonsynchronized nasal intermittent positive pressure ventilation versus continuous positive airway pressure as a primary mode of respiratory support in neonates (26-40 weeks) admitted in a tertiary care center: A randomized controlled trial. Dey, R., Sardar, SK., Kumar Saha, A., et al.[2023]

In a study of 76 preterm neonates with respiratory distress syndrome, early nasal intermittent positive pressure ventilation (NIPPV) significantly reduced the failure rate of respiratory support compared to early continuous positive airway pressure (CPAP), with rates of 13.5% versus 35.9%, respectively.

NIPPV also led to a lower need for intubation and mechanical ventilation within 7 days (18.9% vs. 41%), indicating it may be a more effective intervention for managing respiratory distress in preterm infants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early nasal intermittent positive pressure ventilation versus continuous positive airway pressure for respiratory distress syndrome. Sai Sunil Kishore, M., Dutta, S., Kumar, P.[2022]

In a study of 40 preterm infants receiving nasal high-flow therapy, a standardized weaning protocol resulted in a 91% success rate for weaning, indicating that this approach is effective and safe.

While the electrical activity of the diaphragm (Edi) did not change significantly during gradual flow reductions, there was a notable increase in diaphragm activity immediately after discontinuing high-flow therapy, suggesting that complete cessation may enhance respiratory muscle engagement.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diaphragm electrical activity during weaning of nasal high-flow therapy in preterm infants. Naples, R., Fenton, AC., Brodlie, M., et al.[2023]

NeuroPAP, a new non-invasive ventilation mode, was found to be feasible and well tolerated in 20 stable preterm infants, allowing for continuous adjustment of pressure support based on diaphragm electrical activity.

During NeuroPAP, 78% of breaths were well synchronized with the infants' breathing efforts, significantly improving patient-ventilator synchrony compared to traditional non-invasive positive pressure ventilation (NIPPV), which had only 9% synchronization.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Continuous neurally adjusted ventilation: a feasibility study in preterm infants. Rochon, ME., Lodygensky, G., Tabone, L., et al.[2020]

In a study involving 21 preterm infants, there was no significant difference in breathing effort, as measured by electrical activity of the diaphragm (Edi), between high-flow nasal cannulae (HFNC) and nasal continuous positive airway pressure (nCPAP).

However, the mean respiratory rate was significantly lower during HFNC compared to nCPAP, suggesting that HFNC may be a suitable alternative for weaning preterm infants from respiratory support.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomised cross-over study showed no difference in diaphragm activity during weaning from respiratory support. Brenne, H., Grunewaldt, KH., Follestad, T., et al.[2019]

References

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

Electrical Activity of the Diaphragm in a Small Cohort of Preterm Infants on Noninvasive Neurally Adjusted Ventilatory Assist and Continuous Positive Airway Pressure: A Prospective Comparative Pilot Study. [2020]

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

Comparison of High CPAP versus NIPPV in Preterm Neonates: A Retrospective Cohort Study. [2023]

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

Nonsynchronized nasal intermittent positive pressure ventilation versus continuous positive airway pressure as a primary mode of respiratory support in neonates (26-40 weeks) admitted in a tertiary care center: A randomized controlled trial. [2023]

4. Norway pubmed.ncbi.nlm.nih.gov

Early nasal intermittent positive pressure ventilation versus continuous positive airway pressure for respiratory distress syndrome. [2022]

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

Diaphragm electrical activity during weaning of nasal high-flow therapy in preterm infants. [2023]

6. England pubmed.ncbi.nlm.nih.gov

Continuous neurally adjusted ventilation: a feasibility study in preterm infants. [2020]

7. Norway pubmed.ncbi.nlm.nih.gov

A randomised cross-over study showed no difference in diaphragm activity during weaning from respiratory support. [2019]