Clinical trial NCT05299008: The Effect of Bethanechol on Tracheobronchomalacia
Official title: The Effect of Bethanechol on Work of Breathing and Expiratory Tracheal Collapse in Infants With Tracheobronchomalacia Measured by Electrical Activity of the Diaphragm and Bronchoscopy
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Tracheobronchomalacia
Keywords: bethanechol
swing Edi
Bronchoscopy
Lead sponsor: Arkansas Children's Hospital Research Institute
Sponsor class: OTHER
First posted: 2022-03-28
Enrollment: 20
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Inpatient infants in a level IV Neonatal Intensive Care Unit.

Brief summary: The primary aim of this study is to determine if work of breathing estimated using swing Edi will be improved following initiation of bethanechol in infants with tracheobronchomalacia. The investigators hypothesize that work of breathing will be improved in infants with tracheobronchomalacia estimated by a 20% mean decrease in swing Edi following initiation of bethanechol.

Detailed description: Tracheobronchomalacia (TBM) is characterized by dynamic airway collapse resulting from flaccidity of smooth trachealis muscles, and the incidence in infants has been estimated to be as high as 16-50%. Tracheal collapse results in an increase in work of breathing (WOB) which leads to prolonged ventilatory support, increased caloric needs, and prolonged hospitalization. Clinical signs of increased WOB include nasal flaring, increased use of accessory muscles, and paradoxical movements of the rib cage and abdominal wall. Compared with infants with normal airways, infants with TBM have a higher resistive WOB and require increased respiratory support to help attenuate the respiratory work.

Currently, there are no pharmacologic treatment options approved by the Food and Drug Administration for the treatment of TBM. Animal models have shown that muscarinic agonists may improve the tone of the trachealis muscle and airway mechanics. These physiologic improvements have led to the rationale behind use of the long-acting muscarinic agonist, bethanechol, in the treatment of children with tracheomalacia despite no large trials to demonstrate efficacy. By improving trachealis tone and airway mechanics, infants may benefit from an overall decrease in their resistive WOB leading to improved clinical outcomes.

Measurement of actual WOB can be difficult, invasive, and not easily achieved in neonates, however it can be estimated. One method that has been successfully used to estimate WOB in neonates is by swing electrical activity of the diaphragm (Edi) by neurally adjusted ventilatory assist (NAVA). Swing Edi use in NAVA is the difference between the resting tonic activity of the diaphragm (Edi min) and the peak activity of the diaphragm (Edi max) measured by an Edi catheter. By using Swing Edi as a marker for WOB, the investigators propose a methodology to evaluate a physiologic improvement in infants after starting a pharmacologic treatment for TBM.

Though increased WOB is the result of decreased trachealis tone and tracheal collapse, the most accurate method of identifying airway collapse is by direct visualization of the airways. Bronchoscopy is able to give qualitative and semi quantitative impressions of airway collapsibility and has consistently demonstrated a highly favorable safety profile in infants. By performing bronchoscopy before and after bethanechol initiation a direct change may be noted from medical management.

As such, the investigators hypothesize that WOB estimated by swing Edi and tracheal tone identified by direct visualization bronchoscopy will be improved following initiation of bethanechol in infants with tracheobronchomalacia.

Eligibility criteria: Inclusion Criteria:

* Infants with a diagnosis of tracheobronchomalacia by dynamic computed tomography and showing \> 50% cross-sectional diameter collapse at 40 to 60 post menstrual age and for whom will be treatment with bethanechol in level IV center Neonatal Intensive Care Unit.

Exclusion Criteria:

* Infants with diagnosis of tracheobronchomalacia by dynamic computed tomography with \< 50% cross-sectional diameter collapse at 40 to 60 post menstrual age, or infants in which the medical team has not made the decision to start bethanechol.
* Patients with fixed tracheomalacia or bronchomalacia due to external compression of airways.

Primary outcomes:
measure: The primary aim of this study is to determine if work of breathing estimated using swing Edi will be improved following initiation of bethanechol in infants with tracheobronchomalacia.
timeFrame: 7 days
Secondary outcomes:
measure: Determining if there is a direct visual change in trachealis tone determined by bronchoscopy following bethanechol initiation in infants with tracheobronchomalacia.
timeFrame: Day 1 and then at 7-14 days
measure: Evaluating for change in regional impedance variation by use of Electrical Impedance Tomography
timeFrame: Collect EIT data 24 hours prior to starting bethanechol and on day 7 after starting bethanechol treatment.
measure: Evaluating for change in a Pulmonary Severity Score
timeFrame: Data collected 40 weeks to 60 weeks postmenstrual age
measure: Investigating for change in number of apnea/bradycardia/desaturation events, pain/sedation scores, and doses of sedation medications following bethanechol initiation in infants with tracheobronchomalacia.
timeFrame: Daily from 40 weeks to 60 weeks postmenstrual age
measure: Assessing for side effects of bethanechol treatment such an increase in secretions, wheezing, or an increase in loose stools.
timeFrame: 21 days
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Arkansas Children's Hospital
state: Arkansas
Study officials:
affiliation: Arkansas Children's Hospital Research Institute
name: Charles P Pugh, MD
role: PRINCIPAL_INVESTIGATOR
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