Effect of CPAP on 6-Minute Walk Test Outcomes in Patients With ECAC

Brief Title

Effect of CPAP on 6-Minute Walk Test Outcomes in Patients With ECAC

Official Title

Effect of Continuous Positive Airway Pressure (CPAP) on 6-Minute Walk Test Outcomes in Patients With Excessive Central Airway Collapse (ECAC)

Brief Summary

      The purpose of this protocol is to perform a prospective, randomized, double-blinded,
      pacebo-controlled clinical trial to determine the influence of a non-invasive positive
      pressure ventilation device on exercise capacity and symptoms in adult patients with ECAC.
      Primary outcome will include the total distance traversed by the study subject during a
      standard 6-minute walk test, and secondary outcomes will include peak flow measurement and
      symptom reporting before and after the exercise testing. The study will focus on the use of
      continuous positive airway pressure (CPAP) device. CPAP is FDA-approved for the treatment of
      various medical conditions, including obstructive sleep apnea and heart failure, but is not
      FDA-approved for the treatment of ECAC. The study will enroll 32 ambulatory study subjects
      with confirmed ECAC at the BIDMC, and each study subject will be monitored for up to 3
      months.
    

Detailed Description

      Basal 6MWT performed as a standard of care in these patients will be compared to intervention
      ones to see if there is an improvement of at least 24 meters in their 6MWT distance, then
      both groups will be compared to see if there is a statistically significant difference
      between groups. Subjects, treating physicians and the research fellow performing the 6MWT
      will be blinded to the intervention; the only un-blinded personnel to the intervention will
      be the study coordinator who will be in charge of setting the CPAP before every intervention.

      As part of the standard of care of our institution, patients that are referred due to
      suspicion of ECAC undergo initial PFTs, 6MWT and dynamic CT scan. With this information,
      patients are evaluated in clinic by the interventional pulmonary and thoracic surgery team
      who decide if the patient has the mentioned disease based on the previous testing. To
      corroborate the findings patients with moderate so severe disease are taken into a
      bronchoscopy with dynamic maneuvers as part of the standard of care. Initial bronchoscopic
      examination will be performed as described in the following section "I-Dynamic Bronchoscopy
      Protocol" as part of the standard of care of patients. After initial evaluation, during the
      same intervention, all patients that agree to participate in our study will go through a CPAP
      calibration procedure; in order to determine the adequate pressure to achieve airway patency
      of at least 70% during end exhalation in each individual case. After regular bronchoscopic
      examination, a full face F&P SimplusTM CPAP mask (Fisher & Paykel, Irvine, CA, USA) will be
      placed in all patients to prevent un-blinding the treating physician. The mask will be
      connected to a dual axis swivel adapter (T-adapter) and the bronchoscope will be advanced to
      the nares through the swivel adaptor; air leak will be prevented by the tight disposable cap
      of the swivel adaptor as described by Murgu et al.20

      The calibration process will be performed following the technique first described by Ferguson
      et al10, bronchoscope will be positioned to assess the area with ECAC previously identified
      during regular examination; bronchoscope will be placed in the center of the lumen while
      assuring a constant 1-cm distance between the tip of the bronchoscope and the target area
      being measured, images will be taken during end inspiration and end expiration, gradual
      increases of 1 cmH2O in the CPAP pressure will be made until a 70% or less collapse is seen
      during end expiration by the bronchoscopist. At any given pressure increase the assessment of
      airway collapse will be made in 3 different respiratory cycles, the whole procedure will be
      recorded and posteriorly analyzed using morphometric bronchoscopy (Image J analysis program)
      as described in the "Morphometric Bronchoscopy" section.

      Patient Population Subjects (>18 years of age) with previous diagnosis of ECAC confirmed by
      dynamic CT scan and/or bronchoscopy, who are currently receiving adequate medical therapy
      (Optimal medication doses and interventions defined by Interventional Pulmonary team) for
      comorbidities such as COPD, GERD, asthma, etc and are able to perform a 6 MWT.

      Tracheobronchomalacia Evaluation CT Central Airway Protocol: All patients will be imaged
      according to our standard low dose CT central airway protocol21, which includes imaging
      during end-inspiratory and continuous dynamic expiratory phases. A multidetector row, helical
      CT scanner (LightSpeed; GE Medical Systems; Milwaukee, WI; or Aquilion; Toshiba America
      Medical Systems; Tustin, CA) which includes 4, 8, 16, and 64 detector-row systems will be
      used. Helical scanning will be performed in the cranio-caudal dimension during both
      respiratory phases. An experienced thoracic radiologist will review the CT images on a
      picture archiving and communication system (PACS) [Path-Speed, General Electric Medical
      Systems]. Using a computerized tracing tool in our PACS system, the inner wall of the airway
      will be hand traced at the level of maximal collapse in dynamic expiratory images to
      calculate the cross-sectional area of the airway (mm2). At the same level on end-inspiration
      images, the cross-sectional area of the airway lumen will be determined by using the same
      method. The percentage of luminal collapse between both respiratory phases will be calculated
      using the following formula= [1 - (Aee/Aei)],) X100, where Aee is luminal area at end
      expiration and Aei is luminal area at end inspiration. Mild ECAC is diagnosed if the percent
      of luminal collapse during dynamic expiration is 70-80%, moderate from 80-90% and severe
      >90%.

      I-Dynamic Bronchoscopy Protocol All patients who are enrolled for the study will undergo
      bronchoscopy under minimal sedation using intravenous midazolam and fentanyl to allow
      spontaneous respiration. Lidocaine (1%, 20 ml), will be delivered by atomizer to the
      posterior oropharynx until the gag reflex is suppressed. The larynx, vocal cords,
      aryepiglottic folds and entire tracheobronchial tree will be irrigated with 1% lidocaine in
      2-ml aliquots delivered through the bronchoscope during the procedure. An Olympus BF P180
      video bronchoscope (Olympus America, Melville, NY) with a 4.9-mm outer diameter and 2.0-mm
      working channel will be used to minimize any stenting effect. The bronchoscope will be
      introduced into the proximal trachea at the level of the cricoid. At that point, patients
      will be instructed to take a deep breath, hold it and then blow it out (forced expiratory
      maneuver). Maneuver will be done at the following six sites: proximal trachea at the level of
      the cricoid; mid-trachea 5 cm proximal to the carina; distal trachea 2 cm proximal to the
      carina; right main stem bronchus at the right tracheobronchial angle; bronchus intermedius
      and left main bronchus at the left tracheobronchial angle. The maneuver will be repeated
      three times to ensure maximal airway narrowing during exhalation. All bronchoscopies will be
      video recorded and reviewed after the procedure to assess the degree of airway collapse. Mild
      ECAC is defined as a collapse 70-80%, moderate 80-90% and severe >90% of the airway during
      exhalation. This is standard of care for patients with EDAC.

      After collapse degree is assessed trough forced expiratory maneuver, a nasal CPAP device
      (Define model) will be used in the patient, forced expiratory maneuvers will be repeated with
      different CPAP configurations until a 70% or less airway collapse is achieved. Calibration at
      which 70% airway collapse is achieved will be recorded and posteriorly used as the CPAP
      volume for the second 6MWT.

      Morphometric bronchoscopy Cross-sectional area (CSA) of the airway will be calculated after
      the procedure by using the Image J analysis program (available free of charge at
      http://rsb.info.nih.gov/ij/) using two different measurement techniques as it was described
      by Murgu et al.22 The graphical measurement method uses color levels within the image to
      identify an appropriate region to be measured. Images are imported into Image J and a color
      balance window is opened (Image > Adjust > Color Balance). The histogram is then set to RGB
      color. The minimum and maximum bars are adjusted so that the resulting line corresponds to
      the highest point of the histogram. Only red, yellow, white, and black colors then remain.
      The black area, which represents the region to be measured for CSA, is selected using a wand
      tool. Using the region of interest (ROI) Manager (Analyze > Tools > ROI Manager) the selected
      area is then calculated in pixels. The manual measurement method requires that the operator
      selects the area to be measured by first opening the image using Image J. Using the polygon
      selections tool, the area of interest is then selected, and the ROI manager is used as in the
      graphical method.

      Finally to provide an objective measurement in our patients, a collapsibility index (CI) will
      be calculated: difference in airway lumen size between end inspiration and end expiration: CI
      = (CSAinspir - CSAexpir)/(CSAinspire x 100%). Then measurements obtained for each patient
      during 3 respiratory cycles will be compared to discard that there is any significant
      statistical difference between them.

      Six Minute Walk Test The 6MWT is a test that requires a 100-ft hallway but no exercise
      equipment or advanced training for technicians. It evaluates the global and integrated
      responses of all the systems involved during exercise, including the pulmonary and
      cardiovascular systems, systemic circulation, peripheral circulation, blood, neuromuscular
      units, and muscle metabolism. Testing will be performed by the study personnel in a
      controlled environment. Supplies such as oxygen, sublingual nitroglycerine, aspirin, and
      albuterol (metered dose inhaler or nebulizer) will be available. The distance walked will be
      reported in meters. Data from both groups will be compared in order to verify if CPAP has a
      positive impact on exercise capacity in these patients. Since subjects have never used CPAP
      before and are not used to the device a 10 minute Run-in period will be allowed in which the
      CPAP will be placed while the patient is seating to allow he/she to get used to the sensation
      generated by the machine, at this time the study personnel will also look for air leaks that
      could compromise the results of the study. Either a regular CPAP or a sham-CPAP will be used
      for the Run-in period depending on the result of the randomization; this will be done to
      avoid the patient noticing the difference between this period and the 6 MWT which could
      happen if only regular CPAP was used.

      Sham-CPAP The Sham-CPAP will be created following the methods of Farre et al23 And Rodway et
      al.24 An enlarged air leak incorporated into the exhalation valve will be positioned between
      the mask and the CPAP tubing, allowing airflow resistance of the exhalation port to be almost
      eliminated by increasing its area, thereby virtually cancelling positive pressure. Also an
      orifice restrictor in the CPAP circuit will be connected between the CPAP unit and the tubing
      in order to load the blower with the same airflow resistance as in true CPAP. These changes
      allow the ventilator operating noise and the airflow through the exhalation port remain
      unchanged, which are crucial to a CPAP placebo.

      Enrollment CPAP naïve patients with a diagnosis of ECAC will be informed about the trial and
      if interested will be recruited for our randomized controlled study. Patients who meet the
      inclusion criteria by the principle investigator or co-investigators will be approached
      during an office visit to our Chest Disease Clinic at BIDMC
    


Study Type

Interventional


Primary Outcome

Difference in meters walked in 6MWTs

Secondary Outcome

 Modified Borg scale scores for dyspnea

Condition

Tracheobronchomalacia

Intervention

Continuous positive airway pressure (CPAP) device

Study Arms / Comparison Groups

 Group 1
Description:  This group will perform a 6MWT with CPAP

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Device

Estimated Enrollment

32

Start Date

March 2021

Completion Date

February 2023

Primary Completion Date

January 2023

Eligibility Criteria

        Inclusion Criteria:

          -  Patient with a diagnosis of ECAC either via bronchoscopy or CT Scan

          -  Age > 18 years

          -  Patients that will undergo a diagnostic or therapeutic bronchoscopy as part of their
             standard of care

          -  Patients with a baseline 6 MWT

          -  Patients that have never used CPAP devices in the past

        Exclusion Criteria:

          -  Patients with poorly-controlled respiratory comorbidities (asthma, COPD, obstructed
             sleep apnea, GERD, relapsing polychondritis)

          -  No evidence for acute respiratory tract infection, or respiratory tract infection
             within the prior 3 weeks

          -  Resting bradycardia (<50 beats/min), frequent multifocal PVCs, complex ventricular
             arrhythmia, sustained SVT

          -  Dysrhythmia that might pose a risk during exercise or training

          -  Any disease or condition that interferes with completion of initial or follow-up
             assessments

          -  Subject has co-morbidities that may significantly reduce subject's ability to improve
             exercise capacity (e.g., severe arthritis, planned knee surgery) or baseline
             limitation on 6MWT is not due to dyspnea.

          -  Subject has an inability to walk >140m (150 yd) in 6 minutes

          -  Subject has an inability to tolerate bronchoscopy under moderate sedation or general
             anesthesia.

          -  Subject has a known sensitivity to drugs required to perform bronchoscopy.
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

, , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT04217603

Organization ID

2019P001034


Responsible Party

Principal Investigator

Study Sponsor

Beth Israel Deaconess Medical Center


Study Sponsor

, , 


Verification Date

March 2021