Noninvasive NAVA Versus NIPPV in Low Birthweight Premature Infants

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).

Study Overview

• Status: Terminated
• Conditions: Low Birth Weight; Noninvasive Ventilation
• Intervention / Treatment: Device: Neurally Adjusted Ventilatory Assist; Device: Nasal Intermittent Positive Pressure Ventilation

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.

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Virginia Commonwealth University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: ADULT; OLDER_ADULT; CHILD
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Nasal Intermittent Positive Pressure Ventilation (NIPPV) Mode; After a one hour stabilization period, during which small adjustments to the noninvasive settings can be made to clinically optimize the settings, the study will begin. A Nellcor pulse oximeter probe will be placed on an extremity to provide a continuous non-invasive downloadable measure of saturation (blood oxygen level) and heart rate. Data from the ventilator will be downloaded in real-time to a laptop. These data will be recorded for 4 hours continuously. After that, the ventilator will be switched to the other mode (NIPPV to NAVA), at the same PEEP (positive end-expiratory pressure) and respiratory rate. One hour will be allowed to adjust the ventilator settings. Data will then be collected for 4 hours on the second ventilation mode (NAVA)	Device: Neurally Adjusted Ventilatory Assist; Neurally Adjusted Ventilatory Assist delivered via RAM cannula .; Other Names: NAVA; Device: Nasal Intermittent Positive Pressure Ventilation; Nasal Intermittent Positive Pressure Ventilation delivered via RAM cannula; Other Names: NIPPV
EXPERIMENTAL: Neurally Adjusted Ventilatory Assist (NAVA) Mode; After a one hour stabilization period, during which small adjustments to the noninvasive settings can be made to clinically optimize the settings, the study will begin. A Nellcor pulse oximeter probe will be placed on an extremity to provide a continuous non-invasive downloadable measure of saturation (blood oxygen level) and heart rate. Data from the ventilator will be downloaded in real-time to a laptop. These data will be recorded for 4 hours continuously. After that, the ventilator will be switched to the other mode (NAVA to NIPPV), at the same PEEP and respiratory rate. One hour will be allowed to adjust the ventilator settings. Data will then be collected for 4 hours on the second ventilation mode (NIPPV)	Device: Neurally Adjusted Ventilatory Assist; Neurally Adjusted Ventilatory Assist delivered via RAM cannula .; Other Names: NAVA; Device: Nasal Intermittent Positive Pressure Ventilation; Nasal Intermittent Positive Pressure Ventilation delivered via RAM cannula; Other Names: NIPPV

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Unexpected Events	The number of isolated apneas, bradycardias and desaturations and the number of combined events will be compared by mode of ventilation.	8 hours - from placement on first study ventilation mode to the end of the second study ventilation mode.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Synchronicity	Synchronicity from the ventilator at the time of an event. This will be analyzed to determine whether asynchronicity is related to increased number of events during the study.	8 hours - from placement on first study ventilation mode to the end of the second study ventilation mode.
Asynchronicity Counts	Overall asynchronicity counts will be determined by ventilator data that can be uploaded and analyzed with software supplied by the manufacturer.	During each four hour treatment segment
Average Pressures	Average mean airway pressure and peak inspiratory pressures required in each mode of ventilation.	8 hours - from placement on first study ventilation mode to the end of the second study ventilation mode.

Collaborators and Investigators

• Sponsor: Virginia Commonwealth University
• Investigators: Principal Investigator: Henry J Rozycki, MD, Virginia Commonwealth University

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 15, 2017
• Primary Completion (ACTUAL): September 20, 2017
• Study Completion (ACTUAL): June 30, 2019

Study Registration Dates

• First Submitted: April 17, 2017
• First Submitted That Met QC Criteria: April 26, 2017
• First Posted (ACTUAL): May 2, 2017

Study Record Updates

• Last Update Posted (ACTUAL): November 12, 2019
• Last Update Submitted That Met QC Criteria: November 6, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Body Weight; Birth Weight
• Other Study ID Numbers: HM20005575

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No