Clinical trial NCT06053684: Non-Invasive Ventilation Versus Neurally-Adjusted Ventilatory Assistance (NAVA) for the Treatment of Bronchiolitis
Official title: Comparison of Conventional Non-Invasive Ventilation and Neurally-Adjusted Ventilatory Assistance (NAVA) Non-Invasive Ventilation for the Treatment of Bronchiolitis
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Bronchiolitis
Lead sponsor: Montefiore Medical Center
Sponsor class: OTHER
First posted: 2023-09-26
Enrollment: 120
Sex: ALL
Minimum age (years): 0
Maximum age (years): 2
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Non-blinded, randomized clinical trial
Primary purpose: TREATMENT

Brief summary: This project aims to answer whether the use of a Neurally-Adjusted Ventilatory Assistance mode for non-invasive ventilation in pediatric patients with bronchiolitis results in improved comfort and reduced escalations in therapy (including intubation) when compared to using a standard mode of non-invasive ventilation. Neurally-Adjusted Ventilatory Assistance (NAVA) has been shown to result in greater synchrony then the standard mode of non-invasive ventilation. The study team hypothesizes that this improved synchrony can result in important clinical improvements when NAVA is used to treat children with bronchiolitis.

Detailed description: Bronchiolitis is a common diagnosis in pediatric hospitals and critical care units. Viral infection in younger patients often results in increased work of breathing, hypoxemia, impaired ventilation, and increased secretion burden. In some cases, treatment of severe respiratory failure includes intubation and mechanical ventilation. Current practice for patients with bronchiolitis who require hospital admission is to initially provide non-invasive ventilation to improve the patient's respiratory mechanics. This non-invasive respiratory support can range from simple nasal cannula, to high-flow nasal cannula, to non-invasive positive pressure ventilation.

The high-flow nasal cannula (HFNC) provides warm, humidified, oxygen-enriched air. Therapy commonly is prescribed with a prescribed fraction of inhaled oxygen (FiO2) delivered at 1-2 L/kg/min. This helps to improve oxygenation as the high rate of flow can "wash-out" carbon dioxide in the upper airways and thus reduce the volume of dead space ventilation.

Non-invasive ventilation (NIV) essentially provides a similar method of support as invasive ventilation without the use of endotracheal tube. Prescribed airway support is instead delivered non-invasively through a specialized nasal cannula or for larger children an occlusive facemask of appropriate size. The ventilator provides positive-end expiratory pressure (PEEP) with a prescribed delivery rate of a set inspiratory pressure (positive inspiratory pressure, or pressure control). This ventilator support enables the delivery of a set FiO2, helps maintain open airways to reduce atelectasis and allow for improved oxygenation with better V/Q matching, and improves work of breathing. The ventilator analyzes the flow generated by the patient's inspiratory effort and attempts to provide the prescribed positive inspiratory pressure at the time of the patient's own effort.

One of the major drawbacks of non-invasive ventilation for young pediatric patients with bronchiolitis is the difficulty in achieving synchrony between patient effort and ventilator-delivered positive inspiratory pressure. This is secondary to the large air leak given the non-invasive apparatus and the low inspiratory flows generated by this patient population. Thus, the ventilator and patient are often dyssynchronous which may actually increase work of breathing and agitation while impeding on the ventilatory support provided.

Neurally-Adjusted Ventilatory Assistance (NAVA) attempts to mitigate the harms of ventilator/patient dyssynchrony. This modality utilizes a specialized catheter placed into the esophagus, often via a nasogastric route, which has the capability of monitoring the electrical activity of the patient's diaphragm. This catheter can also be utilized to deliver feeds similarly to a basic nasogastric tube. The NAVA catheter monitors both the activation of the patient's diaphragm (indicating patient respiratory effort) and the strength of this activation in, referred to as the electrical activity of the diaphragm (Edi) and measured in millivolts (µV). Both human and animal studies have positively correlated the peak Edi values with work-of-breathing and demonstrated higher Edi values when respiratory pathology is present . Based on the Edi tracing, the ventilator can then deliver positive inspiratory pressure that is synchronous with both the patient's respiratory effort and proportional to the strength of this effort through a multiplier referred to as the NAVA level on the ventilator. This modality has been shown to improve patient agitation levels, reduce the need for sedating medications, and enhance synchrony in non-invasive ventilation modes.

The current practice model of the investigators entails that patients with bronchiolitis who require more than 1.5 L/kg of HFNC or require non-invasive ventilation, whether via a conventional or NAVA modality, are managed in the Pediatric Intensive Care Unit (PICU). Both modalities for non-invasive ventilation (conventional and NAVA) are used routinely. Patient respiratory status is aggregated into a value known as the Respiratory Severity Score (RSS) which accounts for respiratory rate, dyspnea, retractions, and auscultatory findings adjusted for the age of the patient. The RSS value is a validated assessment tool with good interobserver reliability between Medical Doctors (MDs), Registered Nurses (RNs), and Respiratory Therapists (RTs). It is calculated on a 4-hour basis for all patients with bronchiolitis in the investigator's PICU and helps determine clinical improvement or deterioration and better guide decisions to increase or decrease support.

While multiple physiologic studies demonstrate a reduced work of breathing with invasive NAVA ventilation, the majority of pediatric studies focused on non-invasive NAVA ventilation were designed to determine improvements in patient/ventilator synchronization. The investigators' project aims are two-fold. The study team hypothesizes that Edi levels and RSS scores will positively correlate for patients with bronchiolitis, allowing for another metric to gauge clinical status. The investigators also hypothesizes that the improved synchronization on NAVA-NIV may improve respiratory status as measured by RSS scores and Edi levels, reduce further escalations in respiratory support, shorten the length of non-invasive ventilation required, and reduce intubation rates. This improvement will be more substantial when transitioning from HFNC to NAVA-NIV compared to transitioning to conventional-NIV.

Eligibility criteria: Inclusion Criteria:

* Patients under the age of two years old with a diagnosis of bronchiolitis presenting to the pediatric ICU

Exclusion Criteria:

* Patients unable to utilize a nasogastric tube
* Patients with a diagnosis of chronic lung disease, cyanotic heart lesions, or congestive heart failure
* Patients with hypotonia
* Patients likely to require imminent intubation: \>0.60 Fraction of Inspired Oxygen (FiO2); Carbon Dioxide (CO2) \> 60, frequent apneas, clinician determines patient unlikely to tolerate non-invasive modality)
* Patients with hemodynamic instability, defined as the need for vasoactive medication

Primary outcomes:
measure: Baseline Respiratory Severity Score (RSS)
timeFrame: Approximately one hour after Edi catheter placement
measure: Average Respiratory Severity Score (RSS)
timeFrame: 48 hour average, values collected at ~4 hour intervals.
measure: Baseline Electrical Activity of the Diaphragm (Edi)
timeFrame: Approximately one hour after Edi catheter placement
measure: Average Baseline Electrical Activity of the Diaphragm (Edi)
timeFrame: 48 hour average, values collected at ~4 hour intervals.
Secondary outcomes:
measure: Duration of Non-Invasive Ventilation
timeFrame: Time of randomization or start of non-invasive ventilation (whichever occurs last) up to 4 weeks later or time of intubation (whichever occurs first)
measure: Number of participants requiring intubation
timeFrame: Following start of non-invasive ventilation or randomization (whichever comes last) up to 4 weeks later
measure: Frequency of increasing ventilatory support
timeFrame: From hours 4-48 of the intervention period
measure: Number of patients requiring dexmedetomidine
timeFrame: Through 48 hour study intervention period
Other outcomes:
Locations:
city: Bronx
country: United States
facility: Children's Hospital at Montefiore
state: New York
Study officials:
affiliation: Physician
name: Jacqueline Weingarten, MD
role: PRINCIPAL_INVESTIGATOR
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