Clinical trial NCT03137225: Noninvasive NAVA Versus NIPPV in Low Birthweight Premature Infants
Official title: Noninvasive NAVA Versus NIPPV in Low Birthweight Premature Infants
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Noninvasive Ventilation
Low Birth Weight
Lead sponsor: Virginia Commonwealth University
Sponsor class: OTHER
First posted: 2017-05-02
Enrollment: 1
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Randomization - the order of modes will be assigned based on a random number table using a 5 block design to match the DSMB reporting needs.
Primary purpose: TREATMENT

Brief summary: The investigator hypothesizes that in very low birth weight infants who require respiratory support via noninvasive ventilation, that synchronizing the ventilator breath with the baby's breath using neurally adjusted ventilatory assist (NAVA) will reduce the number and/or severity of apnea/bradycardia/desaturation episodes compared to nasal intermittent positive pressure ventilation (NIPPV).

Detailed description: Very low birthweight (VLBW) premature infants in the NICU (Neonatal Intensive Care Unit) frequently require respiratory support for prolonged periods of time. Invasive mechanical ventilation (which requires intubating the baby with a tube to provide breaths) can lead to ventilator induced lung injury. Because of this, noninvasive respiratory support has become increasingly popular, as this form of ventilation has been shown to reduce the incidence of permanent lung injury.

There are several methods to provide non-invasive support. The gentlest is continual flow of air and oxygen via nasal cannula. However, premature infants often develop apnea, either because the signals from their immature brain are not yet sufficient or because the muscles in the back of their throat do not get enough nerve signals to maintain sufficient opening. As a result, babies on nasal cannula often develop clinical apnea/bradycardia/desaturations. Before putting these babies back on invasive ventilation, clinicians often try to provide the baby with machine breaths while still on non-invasive ventilation.

This method is called nasal intermittent positive pressure ventilation and studies have demonstrated that this method reduces the need for re-intubation in VLBW infants (1) and reduces the rate of apneic events.

A newer method of non-invasive breathing support that has been FDA approved and used in VLBW infants, synchronizes the machine generated breath with the patient's own breath. Neurally adjusted ventilatory assist (NAVA) does this by replacing the standard nasogastric tube with a nasogastric tube that has sensors which detect the baby's natural diaphragm activity, which signal the ventilator to breath in synchronization with the baby. Studies have shown that the efficacy of nasal ventilation is significantly enhanced when the machine breath is synchronized with the patient breath (2). Synchronization also reduces diaphragmatic dysfunction (3). It can improve gas delivery, reduce work of breathing, and make patients demonstrably more comfortable (4).

Neurally Adjusted Ventilatory Assist (NAVA) is a mode of partial support. NAVA can be used both in intubated patients (invasive NAVA) as well as in extubated patients who require noninvasive positive pressure ventilation (noninvasive NAVA) (5). Invasive NAVA has been shown to deliver equivalent ventilation while requiring lower peak inspiratory pressure, as well as reduced respiratory muscle load, compared to conventional pressure support ventilation.

Currently, the choice of using NIPPV or NAVA is at the clinician's discretion. Both are regularly and frequently used in the VCU (Virginia Commonwealth University) Health System's NICU. There are no studies that have examined whether NAVA triggered synchronized ventilation is more effective than nonsynchronized NIPPV. In addition, there is limited data on the synchronicity and mechanics of non-invasive NAVA in VLBW infants. Information comparing clinical and lung mechanical outcomes between NIPPV and NIV (Nasal noninvasive ventilation) NAVA would significantly benefit VLBW care providers and, consequently, their patients in getting the best evidenced based therapy.

Eligibility criteria: Inclusion Criteria:

* \< 1501 grams (VLBW (very low birth weight) infant)
* Patient must be receiving daily caffeine therapy for apnea
* On non-invasive ventilation, either NIPPV or non-invasive NAVA

Exclusion Criteria:

* No concerns for acute sepsis (i.e., blood cultures, if drawn, have been negative for 48 hours, and no active signs/symptoms of sepsis).
* No history of meningitis or seizures
* No signs of increased intracranial pressure, including bulging fontaneIle, presence of ventricular shunt device, or ventriculomegaly by most recent ultrasound.
* Presence of Grade III or IV intraventricular hemorrhage
* No cyanotic heart defects or clinically significant congenital heart disease. Will allow PDA (patent ductus arteriosus), PFO (patent foramen ovale), and mild to moderate ASD (atrial septal defect)/VSD (ventricular septal defect) as determined by pediatric cardiology.
* Non -English speaking legal representatives (parents)

Primary outcomes:
measure: Number of Unexpected Events
timeFrame: 8 hours - from placement on first study ventilation mode to the end of the second study ventilation mode.
Secondary outcomes:
measure: Synchronicity
timeFrame: 8 hours - from placement on first study ventilation mode to the end of the second study ventilation mode.
measure: Asynchronicity Counts
timeFrame: During each four hour treatment segment
measure: Average Pressures
timeFrame: 8 hours - from placement on first study ventilation mode to the end of the second study ventilation mode.
Other outcomes:
Locations:
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
Study officials:
affiliation: Virginia Commonwealth University
name: Henry J Rozycki, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Tang S, Zhao J, Shen J, Hu Z, Shi Y. Nasal intermittent positive pressure ventilation versus nasal continuous positive airway pressure in neonates: a systematic review and meta-analysis. Indian Pediatr. 2013 Apr;50(4):371-6. doi: 10.1007/s13312-013-0122-0. Epub 2012 Oct 5.
citation: Gizzi C, Montecchia F, Panetta V, Castellano C, Mariani C, Campelli M, Papoff P, Moretti C, Agostino R. Is synchronised NIPPV more effective than NIPPV and NCPAP in treating apnoea of prematurity (AOP)? A randomised cross-over trial. Arch Dis Child Fetal Neonatal Ed. 2015 Jan;100(1):F17-23. doi: 10.1136/archdischild-2013-305892. Epub 2014 Oct 15.
citation: Petrof BJ, Jaber S, Matecki S. Ventilator-induced diaphragmatic dysfunction. Curr Opin Crit Care. 2010 Feb;16(1):19-25. doi: 10.1097/MCC.0b013e328334b166.
citation: Stein H, Firestone K. Application of neurally adjusted ventilatory assist in neonates. Semin Fetal Neonatal Med. 2014 Feb;19(1):60-9. doi: 10.1016/j.siny.2013.09.005. Epub 2013 Nov 13.
citation: Moerer O, Beck J, Brander L, Costa R, Quintel M, Slutsky AS, Brunet F, Sinderby C. Subject-ventilator synchrony during neural versus pneumatically triggered non-invasive helmet ventilation. Intensive Care Med. 2008 Sep;34(9):1615-23. doi: 10.1007/s00134-008-1163-z. Epub 2008 May 30.