Non-invasive Neurally Adjusted Ventilatory Assist Versus Nasal Intermittent Positive Pressure Ventilation for Preterm Infants After Extubation

Study Overview
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Brief Summary
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Non-invasive respiratory support has been emerging in the management of respiratory distress syndrome (RDS) in preterm infants to minimise the risk of lung injury. Intermittent positive pressure ventilation (NIPPV) provides a method of augmenting continuous positive airway pressure (CPAP) by delivering ventilator breaths via nasal prongs.It may increase tidal volume, improve gas exchange and reduce work of breathing. However, NIPPV may associate with patient-ventilator asynchrony that can cause poor tolerance and risk of intubation. It may also in increased risk of pneumothorax and bowel perforation because of increase in intrathoracic pressure. On the other hand, neurally adjusted ventilatory assist (NAVA) is a newer mode of ventilation, which has the potential to overcome these challenges. It uses the electrical activity of the diaphragm (EAdi) as a signal to synchronise the mechanical ventilatory breaths and deliver an inspiratory pressure based on this electrical activity. Comparing NI-NAVA and NIPPV in preterm infants, has shown that NI-NAVA improved the synchronization between patient and ventilator and decreased diaphragm work of breathing . There is lack of data on the use of NI-NAVA in neonates post extubation in the literature. To date, no study has focused on short-term impacts. Therefore, it is important to evaluate the need of additional ventilatory support post extubation of NI-NAVA and NIPPV and also the risk of developing adverse outcomes. Aim: The aim is to compare NI-NAVA & NIPPV in terms of extubation failure in infants< 32 weeks gestation. Hypothesis: Investigators hypothesized that infants born prematurely < 32 weeks gestation who extubated to NI-NAVA have a lower risk of extubation failure and need of additional ventilatory support.

Detailed Description
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Study Design: Randomised controlled trial Study Setting: single center NICU level III, KFAFH tertiary care center , Jeddah Saudi Arabia

Official Title
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Non-invasive Neurally Adjusted Ventilatory Assist Versus Nasal Intermittent Positive Pressure Ventilation for Preterm Infants After Extubation: A Randomised Control Trial

Conditions
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Prematurity, Respiratory Failure, Ventilator Lung; Newborn

Intervention / Treatment
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* Device: NI-NAVA
* Device: NIPPV


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Born less than 32 weeks gestation with respiratory distress syndrome (RDS) and requiring endotracheal tube and mechanical ventilation. Less than two weeks old First extubation attempt CRIB score 0-5 Written-informed parental consent for the study Exclusion Criteria: Major congenital malformations or respiratory abnormalities Neuromuscular disease phrenic nerve palsy Intraventricular hemorrhage (IVH) grade III or IV Absence of informed consent Out born infants

Ages Eligible for Study
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Maximum Age: 2 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
Interventional Model Description: Randomised controlled trial A web generated a block randomisation list. A block of 4, stratification based on GA, gender & antenatal steriods Sequentially numbered, opaque and sealed envelopes Restricted access to envelopes
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NI-NAVA<br>Initial setting; NAVA level of 2; PEEP of 5-6 cm H 2 O, apnea time 5-10 seconds, target Edi maximum between 10-15 and minimum < 5 for 72 hours post extubation | Device: NI-NAVA<br>* Enrolled infants will receive Surfactant and loading dose of Caffeine citrate prior to extubation. The criteria for extubation will be as per attending decision. The device is used Servo-I ventilator (MAQUET). FiO 2 % is adjusted to maintain oxygen saturation between 90-94% on pulse oximetry. The flow rate is 8-10 L/min. NAVA electrodes will be inserted within nasogastric catheter & positioned at the level of diaphragm.Vital signs and ventilatory parameters are monitored hourly. Blood gases will be measured before and one hour after extubation<br>|
| Active Comparator: NIPPV<br>Initial setting; PIP can be increased by 2 cm H 2 O from the pre-extubation PEEP of 5-6 cm for 72 hours post extubation | Device: NIPPV<br>* Enrolled infants will receive Surfactant and loading dose of Caffeine citrate prior to extubation. The criteria for extubation will be as per attending decision. The device is used Servo-I ventilator (MAQUET). FiO 2 % is adjusted to maintain oxygen saturation between 90-94% on pulse oximetry. The flow rate is 8-10 L/min. NAVA electrodes will be inserted within nasogastric catheter & positioned at the level of diaphragm.Vital signs and ventilatory parameters are monitored hourly. Blood gases will be measured before and one hour after extubation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment failure | Treatment failure during the first 72 hours post-extubation. Reintubation (failure of extubation) within 72 hours' post extubation. Treatment failure is defined as: Hypoxia (FiO 2 requirement > 0.35) Respiratory acidosis defined as pH < 7.2 & PCo2> 60 mmHg Major apnea requiring mask ventilation or > 4 episodes/ hour. The protocol will discontinue according to treatment failure criteria as mentioned above. Rescue treatment with NIPPV will be allowed and will be considered as treatment failure | 72 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Death prior to discharge | Death | 90 days from birth | 
| Intraventricular haemorrhage IVH (grades III & IV) | defined as haemorrhage causing ventricular dilatation with or without brain parenchymal involvement | 7 days after extubation | 
| Pneumothorax | diagnosed radiologically | 7 days after extubation | 
| Bronchopulmonary dysplasia (BPD) | defined as requirement for supplemental oxygen at 28 days of life or requirement for supplemental oxygen at 36 weeks' postmenstrual age | 36 weeks' postmenstrual age | 
| Necrotizing enterocolitis | defined according to modified Bell's criteria (stage 2 to 3) | 7 days after extubation | 
| Gastrointestinal perforation | diagnosed radiologically or at operation | 7 days after extubation | 
| Nosocomial sepsis | defined as positive blood or cerebrospinal fluid (CSF) cultures taken after five days of age | 7 days after extubation | 
| Retinopathy of prematurity (ROP) | stage 3 or greater (International classification) | 40 weeks corrected postnatal age | 
| Duration of hospitalisation or Length of stay (in days) | Number of days in hospital until first discharge | From admission to first discharge from hospital, assessed up to 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Non-invasive Neurally Adjusted Ventilatory Assist NI-NAVA, Nasal Intermittent Positive Pressure Ventilation NIPPV, post extubation