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

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

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.

Study Overview

• Status: Completed
• Conditions: Respiratory Failure; Prematurity; Ventilator Lung; Newborn
• Intervention / Treatment: Device: NI-NAVA; Device: NIPPV

Detailed Description

Study Design: Randomised controlled trial

Study Setting: single center NICU level III, KFAFH tertiary care center , Jeddah Saudi Arabia

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Saudi Arabia
  • Jeddah, Saudi Arabia, 21159
    • King Fahad Armed Forces Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 2 weeks (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Born less than 32 weeks gestation with respiratory distress syndrome (RDS) and requiring endotracheal tube and mechanical ventilation.
2. Less than two weeks old
3. First extubation attempt
4. CRIB score 0-5
5. Written-informed parental consent for the study

Exclusion Criteria:

1. Major congenital malformations or respiratory abnormalities
2. Neuromuscular disease
3. phrenic nerve palsy
4. Intraventricular hemorrhage (IVH) grade III or IV
5. Absence of informed consent
6. Out born infants

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; 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; 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
Active Comparator: NIPPV; 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; 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: King Fahad Armed Forces Hospital
• Investigators: Principal Investigator: Raniah Aljeaid, King Fahad Armed Forces Hospital Jeddah; Study Director: Nisreen Kafi, King Fahad Armed Forces Hospital Jeddah; Study Director: Fawzia Sabbagh, King Fahad Armed Forces Hospital Jeddah; Study Chair: Mai Abu Seoud, King Fahad Armed Forces Hospital Jeddah

Publications and helpful links

General Publications

• Stein H, Howard D. Neurally adjusted ventilatory assist in neonates weighing <1500 grams: a retrospective analysis. J Pediatr. 2012 May;160(5):786-9.e1. doi: 10.1016/j.jpeds.2011.10.014. Epub 2011 Dec 3.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2017
• Primary Completion (Actual): April 30, 2019
• Study Completion (Actual): April 30, 2019

Study Registration Dates

• First Submitted: December 16, 2017
• First Submitted That Met QC Criteria: December 24, 2017
• First Posted (Actual): January 3, 2018

Study Record Updates

• Last Update Posted (Actual): July 27, 2021
• Last Update Submitted That Met QC Criteria: July 25, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: Non-invasive Neurally Adjusted Ventilatory Assist NI-NAVA; Nasal Intermittent Positive Pressure Ventilation NIPPV; post extubation
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Infant, Newborn, Diseases; Lung Injury; Infant, Premature, Diseases; Ventilator-Induced Lung Injury; Respiratory Insufficiency; Bronchopulmonary Dysplasia
• Other Study ID Numbers: REC 202

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No