Randomized Control Trial: Synchronized Non-invasive Positive Pressure Ventilation Versus Non Synchronized Non Invasive Positive Pressure Ventilation in Extremely Low Birth Weight Infants

Randomized Control Trial: Synchronized Non-Invasive Positive Pressure Ventilation (sNIPPV) With Neurally-Assisted Ventilatory Assist (NAVA) Versus NIPPV in Extremely Low Birth Weight Infants

Infants delivered weighing less than 1 kg at birth (ELBW) are at high risk for the development of bronchopulmonary dysplasia (BPD) and Ventilator-Induced Lung Injury (VILI), in part because of the need for mechanical ventilation utilizing an endotracheal tube (MVET). In spite of strategies to minimize the need for MVET, the incidence of BPD in ELBW infants continues to be 20-80%. The hypothesis is that synchronized NIPPV will decrease the need for MVET and reduce BPD in ELBW infants as compared to NIPPV.

Study Overview

• Status: Completed
• Conditions: BPD - Bronchopulmonary Dysplasia
• Intervention / Treatment: Device: NAVA technology to synchronize NIPPV

Detailed Description

Hypothesis:

The hypothesis is that sNIPPV will decrease the need for MVET and reduce BPD in ELBW infants as compared to NIPPV.

Specific Aims:

The specific aims are to determine whether:

1. sNIPPV results in a decreased need for MVET at 7days of life and 28 days of life in ELBW infants compared to NIPPV.
2. sNIPPV reduces BPD in ELBW infants compared to NIPPV. Research design and methods: ELBW infants will be enrolled in this study at the RNICU at MFCH of WMC following informed written parental consent.

Randomization:

ELBW infants will be randomized to either sNIPPV group or NIPPV group using a computer-generated scheme.

Extubation criteria:

1. Infant is receiving caffeine.

2. Infants can be extubated at any point, but must be extubated following a 12-hour period of clinical stability when the ventilator settings have met all the following criteria:

   • mean airway pressure (MAP) < 8cmH20,
   • FiO2 < 0.4,
   • pH > 7.2, and
   • pCO2 < 70.

Intubation criteria:

Infants must be intubated if any of the following criteria occur:

1. One apneic event requiring positive pressure ventilation (PPV).
2. More than 6 apneic events requiring stimulation within a 6-hour period.

3. A deterioration in respiratory status as noted by any of the following criteria:

   • pH < 7.2,
   • pCO2 > 70,
   • FiO2 > 0.6,
4. Or, if in the opinion of the attending neonatologist, the baby is failing either non-invasive strategy.

Data Collection:

Demographic and outcome data will be collected from source data, and then the patient will be given a unique identifier, without reference to MRN or birthdate.

Tracheal aspirates will be collected per routine nursing care to look for inflammatory cytokine markers (IL8, IL6 and TNF alpha). This may help to determine if certain infants remained intubated due to a pro-inflammatory mechanism (if their TA cytokines were elevated early compared to those who may have been more successfully extubated because of low levels of cytokines).

During hospital stay, DNA and RNA samples will be extracted from buccal swabs, as certain babies are more susceptible to BPD based on their genetic foundations.

Charts will be reviewed to determine the duration of oxygen therapy as well as the duration of MVET.

MVET will be assessed at 7 days of life and 28 days of life as primary outcome. BPD, as defined as oxygen requirement at 36 weeks PMA, is a secondary outcome. Initial statistical analysis will be performed using chi square for categorical data; and t-test or Mann Whitney for continuous data that is normally or non-normally distributed (respectively), with statistical significance when P < 0.05.

Power analysis:

Based on the investigators' NICU data that NIPPV has MVET rate at 7 days of life of 84% for ELBWs, it was hypothesized that sNIPPV will decrease the need for MVET at 7 days of life by 40%. For a power of 80%, and an alpha value of 0.05, the sample size is 27 infants in each group. Anticipating a 10% dropout rate, this gives 30 as the sample size for each group.

Anticipated timeline:

With 80-100 ELBW infants admitted each year, enrollment is anticipated to be completed in 1 year.

The clinical implications of this study will determine if synchronized NIPPV in ELBW infants will reduce the need for mechanical ventilation and ultimately BPD.

There are no procedures, situations, or materials that will be hazardous to personnel. There are no courses planned which support the research training experience. This research will not include the use of experimental drugs or treatments.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Shaili Amatya, MD; Phone Number: 9144938558; Email: shaili.amatya@wmchealth.org
• Study Contact Backup: Name: Lance Parton, MD; Phone Number: 9144938558; Email: Lance.parton@wmchealth.org

Study Locations

• United States
  • New York
    • Valhalla, New York, United States, 10595
      • Westchester Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 months to 6 months (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Babies born less than 1kg.
2. Babies born at 24-30 weeks gestation.

3. Babies who qualify for surfactant administration within 90mins of birth:

   • FiO2 > 0.4,
   • nCPAP > 6, with
   • Increased work of breathing as noted by grunting; and/or inter-, sub-, or supra-sternal retractions.

Exclusion Criteria:

1. Babies with Grade 3-4 IVH (may not be known prior to randomization).
2. Babies with congenital anomalies including neuromuscular disorder.
3. Babies who do not require intubation until 7 days of life.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: NIPPV; non synchronized non invasive positive pressure ventilation
Experimental: NAVA-NIPPV; synchronized non invasive positive pressure ventilation with NAVA	Device: NAVA technology to synchronize NIPPV; Neurally adjust ventilator assist is used to synchronize the NIPPV

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The need for Mechanical Ventilation via ET tube ( MVET) at 7 days of life	Mechanical ventilation via Endotracheal tube	7 days of life
The need for Mechanical Ventilation via ET tube ( MVET) at 28 days of life	Mechanical Ventilation via Endotracheal tube	28 days of life

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of BPD or need for supplemental O2 at 36 weeks corrected age	Bronchopulmonary Dysplasia	36 weeks corrected gestational age

Collaborators and Investigators

• Sponsor: New York Medical College

Study record dates

Study Major Dates

• Study Start (Actual): April 26, 2018
• Primary Completion (Actual): July 26, 2022
• Study Completion (Actual): July 26, 2022

Study Registration Dates

• First Submitted: July 30, 2018
• First Submitted That Met QC Criteria: July 30, 2018
• First Posted (Actual): August 3, 2018

Study Record Updates

• Last Update Posted (Actual): March 27, 2023
• Last Update Submitted That Met QC Criteria: March 24, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Body Weight; Lung Injury; Infant, Premature, Diseases; Ventilator-Induced Lung Injury; Birth Weight; Bronchopulmonary Dysplasia
• Other Study ID Numbers: L12,175

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes