Randomized Control Trial: Synchronized Non-invasive Positive Pressure Ventilation Versus Non Synchronized Non Invasive Positive Pressure Ventilation in Extremely Low Birth Weight Infants
Condition: BPD - Bronchopulmonary Dysplasia
MeSH terms: Bronchopulmonary Dysplasia; Birth Weight
Study type: Interventional

Summary: 
      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.
    

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.
    

Intervention name(s): NAVA technology to synchronize NIPPV
Intervention type(s): Device
Intervention description(s): Neurally adjust ventilator assist is used to synchronize the NIPPV
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Prevention