Non-invasive Ventilation in Preterm Infants

Study Overview
=================
Brief Summary
-----------------
This is a prospective, observational cohort study. For the study part on noninvasive neurally adjusted ventilatory assist (NIV-NAVA) the design is interventional. For all participants prospective data collection will be conducted by chart review and by downloading ventilatory data from the ventilator. A registration of respiratory severity score will be done by a caregiver during the weaning period. This consists of a visual assessment of the work of breathing every 2 hours. For participants on NIV-NAVA consenting to the interventional part of the study a titration procedure will be conducted, afterwards serial electrical impedance tomography and lung and diaphragm ultrasound measurements will be done.

Official Title
-----------------
Non-invasive Ventilation in Preterm Infants

Conditions
-----------------
Premature Birth, Respiratory Distress Syndrome, Ventilator Lung; Newborn

Intervention / Treatment
-----------------
* Diagnostic Test: Titration procedure
* Diagnostic Test: Electrical impedance tomography
* Diagnostic Test: Lung and diaphragm ultrasound


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Preterm infants (< 37 weeks GA) supported with non-invasive respiratory support. Non-invasive respiratory support can consist of non-invasive NAVA, nasal continuous positive airway pressure (nCPAP) or high flow nasal canula (flow > 2 liters/min).The support can be given as primary respiratory support or as respiratory support after weaning from invasive ventilation (= after extubation). Infants can only be enrolled after written and signed informed consent by the parents. Exclusion Criteria: Infant born after a gestational age of 37 weeks or more. Infants with major congenital malformations or chromosomal abnormalities (eg trisomy 18, congenital diaphragmatic hernia…)
Sexes Eligible for Study
-----------------
All

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

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

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Preterm infants on non-invasive respiratory support<br>All infants on non-invasive respiratory support will be studied. Only infants on NIV-NAVA, will undergo an intervention. | Diagnostic Test: Titration procedure<br>* The NAVA level will be reduced to 0,5 cmH2O/microvolt (µV) for 3 minutes as a starting point. Limit peak pressure will be set to 35 cmH2O (the maxi-mum pressure that can be delivered to the patient is cut off at 30 cmH2O). Other ventilator settings will be left unchanged and are as clinically indicated. Starting from a NAVA level of 0,5 cmH20/µV the level will be increased by 0,5 cmH2O/µV every 3 minutes until reaching a maximum NAVA level of 2,5 cmH2O/µV.<br>Diagnostic Test: Electrical impedance tomography<br>* This is a non-invasive technique consisting of the application of a non-adhesive single-use patient belt to monitor regional changes in lung aeration at the bedside.<br>Diagnostic Test: Lung and diaphragm ultrasound<br>* Lung ultrasound is a non-invasive technique used to diagnose lung pathology and to monitor lung condition. This technique is part of the standard of care for preterm infants in our neonatal unit. Lung ultrasound scores are calculated at each time an ultrasound is performed. Ultrasound of the diaphragm consists of a short additional measurement of diaphragm thickness and thickening fraction and will be done at the same time of the lung ultrasound following a standardized procedure.<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total duration of respiratory support | Total number of days of invasive and non-invasive respiratory support | From birth until study completion, variating between 3 weeks and 3 months | 
| Rate of bronchopulmonary dysplasia (BPD) or death | Percentage of infants with BPD or death | From birth until gestational age of 36 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of invasive respiratory support (days) |  | From birth until study completion, variating between 3 weeks and 3 months | 
| Duration of non-invasive respiratory support (days) |  | From birth until study completion, variating between 3 weeks and 3 months | 
| Description of mode of non-invasive respiratory support | Use of NIV-NAVA, CPAP, HHHFNC, oxygen therapy | From birth until study completion, variating between 3 weeks and 3 months | 
| Use of surfactant and mode of administration |  | From birth until study completion, variating between 3 weeks and 3 months | 
| Incidence of nosocomial infection |  | From birth until study completion, variating between 3 weeks and 3 months | 
| Use of corticosteroids for the prevention or treatment of BPD | Use of any corticosteroid (systemic or local) | From birth until study completion, variating between 3 weeks and 3 months | 
| Length of hospital stay | Days of stay in the neonatal unit | From birth until study completion, variating between 3 weeks and 3 months | 
| Respiratory severity score (RSS) | RSS will be measured during the weaning phase of non-invasive respiratory support | From start of the weaning phase until respiratory support is stopped, up to 10 weeks | 
| NIV-NAVA breakpoint | Definition of the breakpoint for patients of NIV-NAVA after following a prespecified titration protocol | At inclusion (within 24 hours) | 
| Lung ultrasound score | Lung ultrasound score will be scored at several time points | At inclusion, day 3, day 7 and weekly thereafter as long as supported with NIV-NAVA, up to 10 weeks | 
| Diaphragm ultrasound | Measurement of diaphragm thickness with ultrasound | At inclusion, day 3, day 7 and weekly thereafter as long as supported with NIV-NAVA, up to 10 weeks | 
| Silent Spaces | Parts (in % of global lung volume) of the lung that are not ventilated as measured with electrical impedance tomography (EIT) | At inclusion, day 3, day 7 and weekly thereafter as long as supported with NIV-NAVA as long as supported with NIV-NAVA, up to 10 weeks | 
| Tidal volume (TV) | Percentage of TV per 'Region of Interest' (ROI) as measured with electrical impedance tomography (EIT) | At inclusion, day 3, day 7 and weekly thereafter as long as supported with NIV-NAVA as long as supported with NIV-NAVA, up to 10 weeks | 
| Center of Ventilation (CoV) | As measured with electrical impedance tomography (EIT) | At inclusion, day 3, day 7 and weekly thereafter as long as supported with NIV-NAVA as long as supported with NIV-NAVA, up to 10 weeks |