Ventilatory Support Methods for Extubation Failure in Preterm Infants

(DIVA Trial)

Recruiting at 20 trial locations

Overseen By Ebuwa O Erebor, MPH

Age: < 18

Sex: Any

Trial Phase: Academic

Sponsor: University of Pennsylvania

Disqualifiers: Congenital anomalies, Neurologic disorders, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 5 days

478 Participants Needed

Trial Summary

What is the purpose of this trial?

DIVA is a pragmatic randomized clinical trial (RCT) to determine: among (P) preterm infants born 23 0/7-28 6/7 weeks gestation undergoing extubation from mechanical ventilation, whether (I) Non-invasive neurally adjusted ventilatory assist (NIV-NAVA) (C) compared with Non-synchronized nasal intermittent positive pressure ventilation (NS-NIPPV), will reduce the incidence of (O) extubation failure within (T) 5 days (120 hours) of extubation.

Will I have to stop taking my current medications?

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

What data supports the effectiveness of the treatment NIV-NAVA for extubation failure in preterm infants?

Research shows that NIV-NAVA, a treatment that helps preterm infants breathe by using signals from their diaphragm, can improve breathing after removing a breathing tube. In one study, 83% of infants had better breathing with lower carbon dioxide levels after using NIV-NAVA. ^{1 2 3 4 5}

Is non-invasive neurally adjusted ventilatory assist (NIV-NAVA) safe for use in preterm infants?

Research on non-invasive neurally adjusted ventilatory assist (NIV-NAVA) in preterm infants suggests it is generally safe, with studies focusing on its effectiveness and adverse effects. While the evidence is less robust compared to invasive methods, no significant safety concerns have been highlighted in the studies available. ^{1 2 3 4 5}

How is the treatment NIV-NAVA different from other treatments for extubation failure in preterm infants?

NIV-NAVA is unique because it uses the electrical activity of the diaphragm (the main muscle used for breathing) to synchronize the ventilator's support with the infant's natural breathing efforts, potentially improving breathing support and reducing the need for reintubation compared to other methods like NCPAP. ^{1 2 3 4 6}

Research Team

Elizabeth Foglia

Principal Investigator

CHOP/UPENN

Eligibility Criteria

The DIVA trial is for preterm infants born between 24 and 27 weeks who were intubated within their first week of life. They must be less than 28 days old when extubated after at least 12 hours on a ventilator. Infants under 500 grams, without consent, needing surgery soon, or with certain health issues can't join.

Inclusion Criteria

I was put on a breathing machine within my first week of life.

I have been on a breathing machine for over 12 hours and am about to be taken off.

The baby is born between 24 and 27 6/7 weeks of pregnancy.

Exclusion Criteria

I have esophageal bleeding or a condition that prevents NG/OG tube placement.

Informed consent not provided

You were born with major birth defects, like underdeveloped lungs.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either NIV-NAVA or NS-NIPPV to prevent extubation failure

5 days

Continuous monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 36 weeks PMA

Long-term follow-up

Monitoring for prematurity-related morbidities and other outcomes

Until 36 weeks PMA

Treatment Details

Interventions

• NIV-NAVA
• NS-NIPPV

Trial Overview This study tests if NIV-NAVA (a type of breathing support that adjusts to the baby's own breathing efforts) is better than NS-NIPPV (non-synchronized nasal ventilation) in preventing failure of extubation within five days in premature infants.

Participant Groups

Group I: NIV-NAVA Experimental Treatment 1 Intervention

Non-invasive neurally adjusted ventilatory assist (NIV-NAVA) is an FDA approved technology that consistently synchronizes non-invasive respiratory support with infant respiratory drive

Group II: NS- NIPPV Active Control 1 Intervention

Non-synchronized nasal intermittent positive pressure ventilation (NS-NIPPV) is an FDA-approved device standardly used in clinical practice at sites to provide an effective mode of non-invasive respiratory support in preterm infants

NIV-NAVA is already approved in United States, Canada for the following indications:

Approved in United States as NIV-NAVA for:

• Prevention of extubation failure in preterm infants

Approved in Canada as NIV-NAVA for:

• Prevention of extubation failure in preterm infants

Who Is Running the Clinical Trial?

University of Pennsylvania

Lead Sponsor

Trials

2,118

Recruited

45,270,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Findings from Research

In a study of 78 preterm infants born at less than 30 weeks of gestation, noninvasive neurally adjusted ventilatory assist (NIV-NAVA) significantly reduced the rate of extubation failure within 72 hours compared to nasal continuous positive airway pressure (NCPAP), with failure rates of 8.6% for NIV-NAVA versus 28.6% for NCPAP.

NIV-NAVA also showed lower electrical activity of the diaphragm (Edi) values at 4, 12, and 24 hours post-extubation, suggesting better respiratory support and efficiency compared to NCPAP.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Noninvasive Neurally Adjusted Ventilation in Postextubation Stabilization of Preterm Infants: A Randomized Controlled Study. Shin, SH., Shin, SH., Kim, SH., et al.[2023]

In a study comparing non-invasive neurally adjusted ventilatory assist (NIV-NAVA) and nasal intermittent positive-pressure ventilation (NIPPV) in preterm infants under 30 weeks gestation, treatment failure rates were similar between the two methods, with 40% for NIV-NAVA and 47.4% for NIPPV, indicating that both methods are effective post-extubation.

NIV-NAVA was found to be safe for use in this population, showing no significant difference in adverse events compared to NIPPV, suggesting it can be a viable option for respiratory support in premature infants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Non-invasive neurally adjusted ventilatory assist versus nasal intermittent positive-pressure ventilation in preterm infants born before 30 weeks' gestation. Yonehara, K., Ogawa, R., Kamei, Y., et al.[2018]

In a study involving 15 preterm infants, neurally adjusted ventilatory assist (NIV-NAVA) demonstrated significantly better patient-ventilator synchrony compared to non-invasive pressure support (NIV-PS), with a much lower trigger delay and reduced asynchrony events.

NIV-NAVA also resulted in less diaphragmatic effort and lower peak inspiratory pressures, indicating it may provide more effective support for preterm infants during non-invasive ventilation, even with large air leaks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Non-invasive neurally adjusted ventilatory assist in preterm infants: a randomised phase II crossover trial. Lee, J., Kim, HS., Jung, YH., et al.[2022]

In a retrospective study of preterm infants at high risk for reintubation, the use of noninvasive neurally adjusted ventilatory assistance (NIV-NAVA) significantly reduced reintubation rates within 72 hours after extubation compared to traditional nasal continuous positive airway pressure (NCPAP) (11.7% vs. 50.0%, p < 0.02).

Despite a longer duration of invasive mechanical ventilation before extubation in the NIV-NAVA group (12.4 days vs. 5.5 days, p < 0.04), there were no significant differences in secondary outcomes such as bronchopulmonary dysplasia (BPD) rates or other complications, suggesting that NIV-NAVA may be a safer and more effective option for these vulnerable infants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is noninvasive neurally adjusted ventilatory assistance (NIV-NAVA) an alternative to NCPAP in preventing extubation failure in preterm infants? Yagui, AC., Gonçalves, PA., Murakami, SH., et al.[2022]

In a study of 24 very low birth weight infants, synchronized noninvasive ventilation using neurally adjusted ventilatory assist (NIV NAVA) significantly improved ventilation postextubation, with 83% of infants showing improved capillary pCO2 levels.

The median pCO2 decreased by 5 mm Hg after increasing NIV NAVA support, indicating that this method effectively supports breathing in premature infants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Noninvasive Neurally Adjusted Ventilatory Assist in Premature Infants Postextubation. Colaizy, TT., Kummet, GJ., Kummet, CM., et al.[2018]

In a study comparing noninvasive ventilation methods for preterm infants, those using neurally adjusted ventilatory assist (NIV-NAVA) had a significantly lower extubation failure rate (6.3%) compared to those on nasal continuous positive airway pressure (NCPAP) (37.5%).

Both groups had similar respiratory severity scores and ventilation parameters at extubation, suggesting that NIV-NAVA may provide a more effective stabilization method post-extubation for preterm infants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of NIV-NAVA and NCPAP in facilitating extubation for very preterm infants. Lee, BK., Shin, SH., Jung, YH., et al.[2020]

References

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

Noninvasive Neurally Adjusted Ventilation in Postextubation Stabilization of Preterm Infants: A Randomized Controlled Study. [2023]

2. Australia pubmed.ncbi.nlm.nih.gov

Non-invasive neurally adjusted ventilatory assist versus nasal intermittent positive-pressure ventilation in preterm infants born before 30 weeks' gestation. [2018]

3. England pubmed.ncbi.nlm.nih.gov

Non-invasive neurally adjusted ventilatory assist in preterm infants: a randomised phase II crossover trial. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Is noninvasive neurally adjusted ventilatory assistance (NIV-NAVA) an alternative to NCPAP in preventing extubation failure in preterm infants? [2022]

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

Noninvasive Neurally Adjusted Ventilatory Assist in Premature Infants Postextubation. [2018]

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

Comparison of NIV-NAVA and NCPAP in facilitating extubation for very preterm infants. [2020]