Comparison of Primary Extubation Failure Between NIPPV and NI-NAVA

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

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).

Study Overview

• Status: Completed
• Conditions: Preterm Infant; Barotrauma; BPD - Bronchopulmonary Dysplasia
• Intervention / Treatment: Other: NAVA; Other: NIPPV

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Florida
    • Jacksonville, Florida, United States, 32207
      • University of Florida

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 months to 8 months (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Infants born between 24 weeks and ≤ 32 weeks completed gestational age or birth weight less than or equal to 1500 grams
2. Postnatal age ≤ 14 days
3. Inborn
4. Mechanically ventilated for at least 12 hrs.
5. Intubated within first 24 hrs. after birth
6. Outborn infants intubated and transferred to UF within 24 hrs. after birth.

Exclusion Criteria:

1. Outborn > 24hrs of age.
2. Failed elective extubation prior to study enrollment
3. Major congenital anomalies or known/suspected chromosomal anomalies
4. Use of paralytics in previous 24 hrs.
5. Participation in another randomized interventional trial
6. Known or suspected phrenic nerve palsy or lesion
7. Known or suspected diaphragmatic lesion
8. Any contraindication to have a nasogastric or orogastric tube placement

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NI-NAVA; 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; Infant will be extubated to NAVA, settings based per protocol
Active Comparator: NIPPV; 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; Infant will be extubated to NIPPV, settings detailed in protocol

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Florida
• Investigators: Principal Investigator: Sanket Shah, MD, University of Florida

Publications and helpful links

General Publications

• Lee J, Kim HS, Jung YH, Shin SH, Choi CW, Kim EK, Kim BI, Choi JH. Non-invasive neurally adjusted ventilatory assist in preterm infants: a randomised phase II crossover trial. Arch Dis Child Fetal Neonatal Ed. 2015 Nov;100(6):F507-13. doi: 10.1136/archdischild-2014-308057. Epub 2015 Jul 15.
• Stein H, Firestone K, Rimensberger PC. Synchronized mechanical ventilation using electrical activity of the diaphragm in neonates. Clin Perinatol. 2012 Sep;39(3):525-42. doi: 10.1016/j.clp.2012.06.004.
• Lemyre B, Davis PG, De Paoli AG, Kirpalani H. Nasal intermittent positive pressure ventilation (NIPPV) versus nasal continuous positive airway pressure (NCPAP) for preterm neonates after extubation. Cochrane Database Syst Rev. 2017 Feb 1;2(2):CD003212. doi: 10.1002/14651858.CD003212.pub3.
• Firestone KS, Beck J, Stein H. Neurally Adjusted Ventilatory Assist for Noninvasive Support in Neonates. Clin Perinatol. 2016 Dec;43(4):707-724. doi: 10.1016/j.clp.2016.07.007.
• LoVerde B, Firestone KS, Stein HM. Comparing changing neurally adjusted ventilatory assist (NAVA) levels in intubated and recently extubated neonates. J Perinatol. 2016 Dec;36(12):1097-1100. doi: 10.1038/jp.2016.152. Epub 2016 Sep 15.
• Firestone KS, Fisher S, Reddy S, White DB, Stein HM. Effect of changing NAVA levels on peak inspiratory pressures and electrical activity of the diaphragm in premature neonates. J Perinatol. 2015 Aug;35(8):612-6. doi: 10.1038/jp.2015.14. Epub 2015 Mar 12.
• 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.
• Baudin F, Pouyau R, Cour-Andlauer F, Berthiller J, Robert D, Javouhey E. Neurally adjusted ventilator assist (NAVA) reduces asynchrony during non-invasive ventilation for severe bronchiolitis. Pediatr Pulmonol. 2015 Dec;50(12):1320-7. doi: 10.1002/ppul.23139. Epub 2014 Dec 8.
• Bhandari V. Nasal intermittent positive pressure ventilation in the newborn: review of literature and evidence-based guidelines. J Perinatol. 2010 Aug;30(8):505-12. doi: 10.1038/jp.2009.165. Epub 2009 Oct 22. Erratum In: J Perinatol. 2010 Dec;30(12):827.

Study record dates

Study Major Dates

• Study Start (Actual): October 23, 2017
• Primary Completion (Actual): September 5, 2019
• Study Completion (Actual): September 5, 2019

Study Registration Dates

• First Submitted: July 28, 2017
• First Submitted That Met QC Criteria: August 1, 2017
• First Posted (Actual): August 8, 2017

Study Record Updates

• Last Update Posted (Actual): February 19, 2020
• Last Update Submitted That Met QC Criteria: February 17, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Keywords: Extubation; NAVA; NIPPV
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Wounds and Injuries; Infant, Newborn, Diseases; Lung Injury; Infant, Premature, Diseases; Ventilator-Induced Lung Injury; Bronchopulmonary Dysplasia; Barotrauma
• Other Study ID Numbers: IRB201701971

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: No