Neurally Adjusted Ventilatory Assist for Neonates With Congenital Diaphragmatic Hernias

Study Overview
=================
Brief Summary
-----------------
Congenital Diaphragmatic Hernias (CDH) are typically repaired surgically in the first few days of a neonate's life. Following surgical repair, infants usually require ventilatory support to ensure adequate oxygenation. Traditionally assist control ventilation (ACV) has been used to support neonates with CDH. Due to delivering a fixed pressure of oxygen, ACV has been associated with barotrauma and long-term lung damage. A more recent approach to ventilation is non-invasive neurally adjusted ventilatory assist (NIV-NAVA). NIV-NAVA uses electrical signals of the diaphragm to deliver a proportional pressure of oxygen. Our dual-centre randomised cross-over trial aims to investigate the efficacy of NIV-NAVA compared to ACV for supporting neonates with CDH.

Detailed Description
-----------------
Background: Congenital Diaphragmatic Hernias (CDH) are typically repaired surgically in the first few days of a neonate's life. Following surgical repair, infants usually require ventilatory support to ensure adequate oxygenation. Traditionally assist control ventilation (ACV) has been used to support neonates with CDH. Due to delivering a fixed pressure of oxygen, ACV has been associated with barotrauma and long-term lung damage. A more recent approach to ventilation is non-invasive neurally adjusted ventilatory assist (NIV-NAVA). NIV-NAVA uses electrical signals of the diaphragm to deliver a proportional pressure of oxygen. Evidence suggests that NAVA may reduce physiological parameters associated with lung pressure and hence reduce the risk of iatrogenic lung injury. Aims: Our aim is to compare the oxygenation index (OI) of neonates with CDH, ventilated with ACV and NIV-NAVA. The OI is calculated as the fractured of inspired oxygen x mean airway pressure x partial pressure of oxygen/100. The oxygenation index is used as a marker of hypoxic respiratory failure in infants with CDH and forms the basis of the criteria to administer nitric oxide. Methods: Our investigation is a dual-centre randomised cross-over trial. Infants will be identified and parents counselled in the first few days following delivery. Neonates that meet inclusion criteria will be randomised to receive either NIV-NAVA or ACV first, followed by the other method of ventilation. Infants will be stabilised on ACV one-hour prior to entering the trial. On entry into the trial, they will receive 4-hours of each ventilatory method with a 20-minute stabilisation break in between.

Official Title
-----------------
Neurally Adjusted Ventilatory Assist for Neonates With Congenital Diaphragmatic Hernias

Conditions
-----------------
Congenital Diaphragmatic Hernia

Intervention / Treatment
-----------------
* Device: Neurally Adjusted Ventilatory Assist
* Device: Assist Control Ventilation


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Infants born with congenital diaphragmatic hernia more than 34-weeks gestation Exclusion Criteria: Receiving Nitric Oxide Requiring an FIO2 more than 80% to maintain SpO2: 85-95%. Severe chromosomal abnormality Severe cardiac anomalies requiring corrective surgery Renal anomalies Skeletal deformities suspected to impede thoracic or lung development Severe central nervous system anomalies suspected to impede diaphragmatic signalling Use of neuromuscular blocking agents Contraindication to nasogastric tube insertion

Ages Eligible for Study
-----------------
Minimum Age: 1 Minute
Maximum Age: 28 Days

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: Dual Centre Randomised Cross-Over Trial. Infants that meet inclusion criteria will be randomised to be ventilated with either NIV-NAVA or ACV for four hours, followed by the second mode of ventilation. There will be a 20-minute stabilisation period between ventilatory methods.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Neurally Adjusted Ventilatory Assist<br>Infants will first be ventilated with NAVA for four hours. Following this, they will undergo a 20-minute stabilisation period prior to ventilating with assist control ventilation (ACV). | Device: Neurally Adjusted Ventilatory Assist<br>* NAVA uses electrical signals of the diaphragm to deliver a proportional pressure of oxygen, to which proportion is set by the clinician as the NAVA level.<br>* Other names: Assist Control Ventilation;Device: Assist Control Ventilation<br>* ACV delivers fixed oxygen pressure set by the clinician at the start of each inspiratory breath.<br>|
| Experimental: Assist Control Ventilation (ACV)<br>Infants will first be ventilated with ACV for four hours. Following this, they will undergo a 20-minute stabilisation period prior to ventilating with non-invasive neurally adjusted ventilatory assist. | Device: Neurally Adjusted Ventilatory Assist<br>* NAVA uses electrical signals of the diaphragm to deliver a proportional pressure of oxygen, to which proportion is set by the clinician as the NAVA level.<br>* Other names: Assist Control Ventilation;Device: Assist Control Ventilation<br>* ACV delivers fixed oxygen pressure set by the clinician at the start of each inspiratory breath.<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Oxygenation Index (OI) | Oxygenation Index is calculated as MAP x FIO2 x PaO2/100. MAP is the mean airway pressure. FIO2 represents the concentration of inspired oxygen and PAO2 is the partial pressure of oxygen. The OI is a reliable indicator of lung function, previous research has shown its use in the prognostication of neonates with CDH. | Infants will receive each mode of ventilation for four hours. OI will be recorded every 5-minutes for the final 30-minutes of each ventilation period. The OI will be averaged over the 30-minute time frame. This average OI will then be compared. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Respiratory Severity Score (RSS) | The respiratory severity score is calculated as RSS = FIO2 x MAP. Where FIO2 represents the fraction of inspired oxygen and MAP is the mean airway pressure. In one multivariate analysis of 59 infants with CDH, RSS was an effective prognostic marker. | RSS will be recorded every 5-minutes for the final 30-minutes that the infant is on each ventilation mode. This will be compared to their baseline 30-minutes pre-randomisation and between ventilation modes. |