The Effect of Bethanechol on Tracheobronchomalacia

January 29, 2024 updated by: Charles Preston Pugh, Arkansas Children's Hospital Research Institute

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Observational

Enrollment (Estimated)

20

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • Arkansas
      • Little Rock, Arkansas, United States, 72202
        • Recruiting
        • Arkansas Children's Hospital
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Probability Sample

Study Population

Inpatient infants in a level IV Neonatal Intensive Care Unit.

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Infants with diagnosis of tracheobronchomalacia treated with bethanechol
Infants with a diagnosis of tracheobronchomalacia by dynamic computed tomography and showing > 50% cross-sectional diameter collapse at 40 to 60 post menstrual age
Drug: Bethanechol
Infants whom will be treated with bethanechol for tracheobronchomalacia in level IV center Neonatal Intensive Care Unit.
Other Names:
  • bethanechol chloride

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Time Frame: 7 days
Swing Edi data will be collected continuously by downloading ventilator trends from the 24 hours prior to initiation of bethanechol in infants and subsequently downloaded every 48-72 hours for 7 days after starting bethanechol.
7 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Determining if there is a direct visual change in trachealis tone determined by bronchoscopy following bethanechol initiation in infants with tracheobronchomalacia.
Time Frame: Day 1 and then at 7-14 days
A baseline flexible bronchoscopy prior to starting of bethanechol followed by a repeat flexible bronchoscopy at days 7-14 of post bethanechol treatment.
Day 1 and then at 7-14 days
Evaluating for change in regional impedance variation by use of Electrical Impedance Tomography
Time Frame: Collect EIT data 24 hours prior to starting bethanechol and on day 7 after starting bethanechol treatment.
Electrical Impedance Technology (EIT) is a tool used to monitor regional changes in ventilation and lung mechanics.
Collect EIT data 24 hours prior to starting bethanechol and on day 7 after starting bethanechol treatment.
Evaluating for change in a Pulmonary Severity Score
Time Frame: Data collected 40 weeks to 60 weeks postmenstrual age
Evaluate a change in a Pulmonary Severity Score (Madden 2005). The pulmonary severity score is defined as the fraction of inspired oxygen (FIO2) x (support) x (medications).
Data collected 40 weeks to 60 weeks postmenstrual age
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.
Time Frame: Daily from 40 weeks to 60 weeks postmenstrual age
Data collected 40 weeks to 60 weeks postmenstrual age
Daily from 40 weeks to 60 weeks postmenstrual age
Assessing for side effects of bethanechol treatment such an increase in secretions, wheezing, or an increase in loose stools.
Time Frame: 21 days
Collect the documented effects 7 days before and 14 days after bethanechol initiation.
21 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Arkansas Children's Hospital Research Institute

Investigators

  • Principal Investigator: Charles P Pugh, MD, Arkansas Children's Hospital Research Institute

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 11, 2022

Primary Completion (Estimated)

June 30, 2024

Study Completion (Estimated)

June 30, 2024

Study Registration Dates

First Submitted

March 18, 2022

First Submitted That Met QC Criteria

March 18, 2022

First Posted (Actual)

March 28, 2022

Study Record Updates

Last Update Posted (Actual)

January 30, 2024

Last Update Submitted That Met QC Criteria

January 29, 2024

Last Verified

January 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 274192

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Tracheobronchomalacia

Clinical Trials on Bethanechol

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Egypt

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe