NAVA vs. CMV Crossover in Severe BPD

Study Overview
=================
Brief Summary
-----------------
This prospective, unblinded, pilot randomized cross-over trial of 2 modes of mechanical ventilation will compare measures of pulmonary mechanics, respiratory gas exchange, and patient comfort between conventional flow triggered mechanical ventilation and neurally adjusted ventilatory assist (NAVA) among 20 prematurely born infants and young children receiving invasive respiratory support for severe bronchopulmonary dysplasia (BPD).

Detailed Description
-----------------
Most research to date in neonatal lung disease has focused on bronchopulmonary dysplasia (BPD) prevention. As a result, insufficient investigation has been performed to define optimal respiratory management strategies for infants and young children with established BPD. Thus, there is no robust evidence base to guide ventilator management to promote lung disease recovery and support neurodevelopment in this population. Neurally adjusted ventilatory assist (NAVA) is an alternative to conventional flow triggered ventilation that has shown promise for improving respiratory gas exchange, patient-ventilator interaction, and work of breathing in preterm neonates. The safety and efficacy of NAVA in infants and young children with established, severe BPD is uncertain. This prospective, unblinded, pilot randomized cross-over trial of 2 modes of mechanical ventilation will compare measures of pulmonary mechanics, respiratory gas exchange, and patient comfort between conventional flow triggered mechanical ventilation and NAVA among 20 prematurely born infants and young children receiving invasive respiratory support for severe BPD.

Official Title
-----------------
Pilot Cross-Over Trial of Neurally Adjusted Ventilatory Assist (NAVA) and Conventional Flow Triggered Mechanical Ventilation (CMV) in Severe Bronchopulmonary Dysplasia (sBPD)

Conditions
-----------------
Bronchopulmonary Dysplasia, Neurally Adjusted Ventilatory Assist, Mechanical Ventilation

Intervention / Treatment
-----------------
* Device: NAVA
* Device: CMV


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Gestational ages (GA) ≤ 32 weeks Current age between 36 weeks postmenstrual age (PMA) and 2 years corrected age Severe BPD [as per National Institutes of Health (NIH) consensus definition] diagnosed at 36 weeks postmenstrual age Receiving invasive mechanical ventilation for ongoing lung disease Not expected to be ready for extubation within 11 days following enrollment Parental consent Exclusion Criteria: Severe congenital anomalies Known diaphragmatic defect Current treatment with high frequency mechanical ventilation Do not resuscitate (DNR) Status or Futility of Care >10% leak around the artificial airway, Treatment with neuromuscular blockade within 72 hours prior to enrollment Acute respiratory instability defined as a ventilator rate increase > 15 beats per minute (bpm), Positive end-expiratory pressure (PEEP) increase > 2 cm/water (H2O), sustained FiO2 increase > 20%, and/or prescribed increase in tidal volume > 2 mL/kg within 24 hours prior to enrollment will be excluded.

Ages Eligible for Study
-----------------
Maximum Age: 24 Months

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Prospective, unblinded, pilot randomized cross-over trial of 2 modes of mechanical ventilation
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Conventional Flow Triggered Mechanical Ventilation (CMV)<br>Subjects will be ventilated with conventional mechanical ventilation with data collected for the 5 day time frame to compare to the experimental arm | Device: CMV<br>* CMV mode of mechanical ventilation that provides a trigger for a spontaneous breath from the airway flow sensor with dynamics of the breath set as required by the mode<br>* Other names: Conventional Flow Triggered Mechanical Ventilation;|
| Experimental: Neurally Adjusted Ventilatory Assist (NAVA)<br>Subjects will be ventilated on neurally adjusted ventilatory assist (NAVA) mode with data collected for the 5 day time frame to compare with placebo arm | Device: NAVA<br>* NAVA mode of mechanical ventilation provide the trigger for a spontaneous breath from the diaphragmatic movement instead of diaphragm and allows the patient to control the dynamics of the breath generally set in CMV mode.<br>* Other names: Neurally Adjusted Ventilatory Assist;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Oxygen saturation (SpO2) index | Oxygen saturation index will be measured by assessing if invasive mechanical ventilation with NAVA compared to CMV improves respiratory gas exchange in patients receiving invasive respiratory support for BPD. This will be calculated as the median, time-weighted daily oxygen saturation (SpO2) index ([mean airway pressure x Fraction of inspired oxygen (FiO2)]/SpO2). | up to 5 days per study arm | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sedation Medications | The need for sedation medication will be assessed by comparing the needs for sedation by the total daily dose milligram/kilogram (mg/kg) of sedation medications on invasive mechanical ventilation with NAVA compared to CMV. | up to 5 days per study arm | 
| Stress | Patient stress will be assessed by collecting salivary swabs three times per day to measure cortisol levels. The daily average will be assessed and compared as a marker for patient stress on invasive mechanical ventilation with NAVA compared to CMV. | up to 5 days per study arm | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
BPD, Bronchopulmonary Dysplasia