Comparison of Primary Extubation Failure Between NIPPV and NI-NAVA

Study Overview
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Brief Summary
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Extubation failure is a significant problem in preterm neonates and prolonged intubation is a well-documented risk factor for development of chronic lung disease. Out of the respiratory modalities available to extubate a preterm neonate; high flow nasal canula, nasal continuous positive airway pressure (nCPAP) and noninvasive positive pressure ventilation (NIPPV) are the most commonly used. A recent Cochrane meta-analysis concluded that NIPPV has lower extubation failure as compared to nCPAP (30% vs. 40%) NAVA (neurally adjusted ventilatory assist), a relatively new mode of mechanical ventilation in which the diaphragmatic electrical activity initiates a ventilator breath and adjustment of a preset gain (NAVA level) determines the peak inspiratory pressure. It has been reported to improve patient - ventilator synchrony and minimize mean airway pressure and ability to wean an infant from a ventilator. However till date there has been no head to head comparison of extubation failure in infants managed on NAVA with conventional ventilator strategies. In this study the investigators aim to compare primary extubation failure rates in infants/participants managed by NIPPV vs. NI-NAVA (non invasive NAVA). Eligible infants/participants will be randomized to be extubated to predefined NIPPV or NI-NAVA ventilator settings and will be assessed for primary extubation failure (defined as reintubation within 5 days after an elective extubation).

Detailed Description
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Mechanical ventilation is needed for most preterm infants to maintain adequate oxygenation and ventilation. However the coexistence of lung immaturity, weak respiratory drive, excessively compliant chest wall, and surfactant deficiency often contribute to dependency on mechanical ventilation during the first days or weeks after birth. Prolonged mechanical ventilation is associated with high mortality and morbidities including ventilator-associated pneumonia, pneumothorax, and bronchopulmonary dysplasia (BPD). Each additional week of mechanical ventilation is reported to be associated with an increase in the risk of neurodevelopmental impairment. Reduction in the need and duration of invasive mechanical ventilation may potentially improve outcome of preterm infants. Extubation failure has been independently associated with increased mortality, longer hospitalization, and more days on oxygen and ventilatory support. It is critical, therefore, to attempt extubation early and at a time when successful extubation is likely. A recent Cochrane review compared the use of nasal intermittent positive pressure ventilation (NIPPV) with nasal continuous positive airway pressure (nCPAP) in preterm infants after extubation and found that NIPPV may be more effective than nCPAP at decreasing extubation failure. The feasibility of NAVA use has been described in neonatal and pediatric patients. Several studies cite a decrease in peak inspiratory pressures, improved synchrony in triggering, and more appropriate termination of positive pressure support. Some studies have reported lower work of breathing, PaO2/FiO2 ratios (partial pressure of oxygen/ fractional inspired oxygen)and MAP. In addition, NAVA has been used for patients who fight the ventilator, and the synchrony improves the ability to wean. The use of NIV-NAVA in neonates has promise as a primary mode of ventilation to aid in the prevention of intubation and also maintaining successful extubation. Early extubation may be enhanced with NIV-NAVA of those neonates requiring intubation for numerous reasons. The ability to provide synchronous NIV allows clinicians the opportunity to extubate infants earlier with increased confidence than with previous post extubation support. However there is lack of scientific evidence on extubation failure rates on NI-NAVA. Trials comparing NAVA to conventional ventilators with regard to ventilator associated lung injury, ventilator associated pneumonia and decreasing duration of time on the ventilator have not yet been reported.

Official Title
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Comparison of Primary Extubation Failure Between Non-invasive Positive Pressure Ventilation (NIPPV) and Non Invasive Neural Access Ventilatory Assist (NI-NAVA)

Conditions
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Preterm Infant, BPD - Bronchopulmonary Dysplasia, Barotrauma

Intervention / Treatment
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* Other: NAVA
* Other: NIPPV


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Infants born between 24 weeks and ≤ 32 weeks completed gestational age or birth weight less than or equal to 1500 grams Postnatal age ≤ 14 days Inborn Mechanically ventilated for at least 12 hrs. Intubated within first 24 hrs. after birth Outborn infants intubated and transferred to UF within 24 hrs. after birth. Exclusion Criteria: Outborn > 24hrs of age. Failed elective extubation prior to study enrollment Major congenital anomalies or known/suspected chromosomal anomalies Use of paralytics in previous 24 hrs. Participation in another randomized interventional trial Known or suspected phrenic nerve palsy or lesion Known or suspected diaphragmatic lesion Any contraindication to have a nasogastric or orogastric tube placement

Ages Eligible for Study
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Minimum Age: 24 Weeks
Maximum Age: 32 Weeks

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NI-NAVA<br>Wait to meet extubation criteria within 14 days postnatal age Pre-extubation mode of invasive ventilation will be per physician discretion (NAVA, CMV, high frequency oscillator ventilation (HFOV) or high frequency jet ventilation (HFJV)) Pi to determine eligibility or exclusion Randomize to either NIPPV or NI-NAVA, 1:1 randomization PI will not be blinded to the intervention (not feasible) If extubating to NAVA then place the catheter to optimize position and Edi 1 hr. prior to planned extubation. ABG or CBG to be obtained at 4 hrs. post extubation NI-NAVA settings will be weaned or increased as the clinical situation demands and outlined in the protocol | Other: NAVA<br>* Infant will be extubated to NAVA, settings based per protocol<br>|
| Active Comparator: NIPPV<br>Wait to meet extubation criteria within 14 days postnatal age Pre-extubation mode of invasive ventilation will be per physician discretion (NAVA, CMV, high frequency oscillator ventilation (HFOV) or high frequency jet ventilation (HFJV)) PI to determine eligibility or exclusion Randomize to either NIPPV or NI-NAVA, 1:1 randomization PI will not be blinded to the intervention (not feasible) ABG or CBG to be obtained at 4 hrs. post extubation NIPPV settings will be weaned or increased as the clinical situation demands and outlined in the protocol | Other: NIPPV<br>* Infant will be extubated to NIPPV, settings detailed in protocol<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Extubation success | assess how many infants stayed extubated at 5 days after extubation | 5 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bronchopulmonary dysplasia (BPD) | based on NIH guidelines | until discharge / 36 weeks post menstrual age | 
| Ventilator Days | days on positive pressure ventilation | until discharge / 36 weeks post menstrual age | 
| NICU length of stay | discharge or death or transfer | until discharge / 36 weeks post menstrual age | 
| Patent ductus arteriosus (PDA) | echo diagnosed/confirmed | until discharge / 36 weeks post menstrual age | 
| Necrotizing enterocolitis (NEC | confirmed on Xray | until discharge / 36 weeks post menstrual age | 
| Late onset sepsis | only culture proven | until discharge / 36 weeks post menstrual age | 
| Gastrointestinal perforation | confirmed on X-ray or surgical exploration | until discharge / 36 weeks post menstrual age | 
| Mortality | all causes within NICU stay | until discharge / 36 weeks post menstrual age | 
| Extubation failure at 3 days | reintubation by 72 hrs. post extubation | until discharge / 36 weeks post menstrual age | 
| Extubation failure at 7 days | reintubation by 72 hrs. post extubation | until discharge / 36 weeks post menstrual age | 
| Pulmonary air leak | including pulmonary interstitial emphysema (PIE) pneumomediastinum and pneumothorax | until discharge / 36 weeks post menstrual age | 
| Severe intraventricular hemorrhage | on cranial ultrasound, worst grade | until discharge / 36 weeks post menstrual age | 
| Abdominal distension > 2cm from baseline and with signs necessitating cessation of feeds during the first 48 hrs. after extubation | during the first 48 hrs. after extubation | until discharge / 36 weeks post menstrual age | 
| Retinopathy of prematurity (ROP) | ophthalmologic exam | until discharge / 36 weeks post menstrual age | 
| Ventilator associated Pneumonia (VAP) | diagnosed based on tracheal culture + CXR changes + clinical worsening + treatment | until discharge / 36 weeks post menstrual age | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NAVA, Extubation, NIPPV