Hyperbaric Oxygen Therapy for Lung Transplantation

Hyperbaric Oxygen Therapy for Lung Transplantation-Associated Pseudomembranes and Central Airway Stenosis

The objective of this study is to evaluate the effect of hyperbaric oxygen therapy (HBOT) on airway complications in post-lung transplant recipients with evidence of restricted levels of blood and oxygen in the airway tissue. Study subjects with extensive airway tissue damage in the early post-transplant period will be randomized to HBOT or usual care and followed clinically for 12 months following randomization. The investigators hypothesize that HBOT will decrease the number of airway complications in the treated subjects.

Study Overview

• Status: Completed
• Conditions: Central Airway Stenosis; Disorder Related to Lung Transplantation; Airway Exudative Plaques; Airway Complications Post-Lung Transplantation
• Intervention / Treatment: Drug: Hyperbaric Oxygen Therapy; Procedure: Endobronchial Biopsy of Airway Epithelium

Detailed Description

Hyperbaric oxygen therapy (HBOT) will be performed with the standard HBOT protocol used at Duke for the treatment of compromised grafts and flaps. This is 2 hours of breathing >99% medical grade oxygen inside an air-pressurized chamber at atmospheric pressure of 2 once a day for 20 sessions. These sessions will be scheduled 3-5 times per week, depending on the availability of the patient and the hyperbaric medicine physician. The HBOT procedure used for this study will be identical to that used for clinical practice in the Duke University Health System Center for Hyperbaric Medicine and Environmental Physiology, including the oxygen that is used in the chamber. Patients will receive treatment through the regular clinical hyperbaric service. These are routine, not special, treatment sessions and they will receive them alongside other Duke University Medical Center patients being treated for other reasons. The medical grade oxygen used is a part of the Duke University Health System Center for Hyperbaric Medicine and Environmental Physiology hyperbaric chamber system.

While the patients randomized to receive usual care will not undergo HBOT, both study groups will receive standard serial bronchoscopies for airway clearance and for the collection of bronchoalveolar lavage fluid for culture data, due to the high rate of infection in lung transplant patients. All subjects will undergo the standard surveillance bronchoscopies every 3 to 4 weeks (x3) for clearance of the exudate from the airway, as well as monitoring progression of the airway abnormalities. As participants in this study, an, endobronchial biopsy of the airway epithelium will be performed at the main carina to collect a sample of recipient epithelium as well as at the first subcarina for each donor lung. Three samples will be collected from each of the biopsy sites. These samples are small (1 to 2 mm) and are thought to have a minimal clinical risk of minor bleeding associated with the procedure. Biopsy will add roughly 3 minutes total to each procedure.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Post-lung transplant patient
• Extensive exudative plaques at 1 month bronchoscopy
• No sign of airway improvement, or showing worsening of plaques at follow-up bronchoscopy 2-3 weeks after 1 month bronchoscopy.

Exclusion Criteria:

• Use of mechanical ventilation with fraction of inspired oxygen(FiO2) greater than 40%
• Use of extracorporeal membrane oxygenation
• Use of inhaled nitric oxide
• Presence of pneumothorax
• Pregnancy
• Inability to provide informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Hyperbaric Oxygen, Airway Biopsy; The hyperbaric oxygen therapy (HBOT) will be performed with the standard HBOT protocol used at Duke for the treatment of compromised grafts and flaps. This is 2 hours of breathing >99% medical grade oxygen inside an air-pressurized chamber at atmospheric pressure of 2 (2 ATA) once a day for 20 sessions. These sessions will be scheduled 3-5 times per week, depending on the availability of the patient and the hyperbaric medicine physician. During standard bronchoscopies, an endobronchial biopsy of the airway epithelium will be performed. Biopsy will add roughly 3 minutes total to each procedure.	Drug: Hyperbaric Oxygen Therapy; 2 hours of breathing >99% medical grade oxygen inside an air-pressurized chamber at 2 ATA once a day for 20 sessions. These sessions will be scheduled 3-5 times per week, depending on the availability of the patient and the hyperbaric medicine physician.; Other Names: HBOT; Hyperbaric Oxygen; Procedure: Endobronchial Biopsy of Airway Epithelium; During standard post-transplantation bronchoscopies, participants in this study will undergo an endobronchial biopsy of the airway epithelium for each donor lung.; Other Names: Airway Biopsy
Other: No Hyperbaric Oxygen, Airway Biopsy; No hyperbaric oxygen therapy administered, but lung biopsy still completed during standard post-lung transplant bronchoscopies. An endobronchial biopsy of the airway epithelium will be performed. Biopsy will add roughly 3 minutes total to each procedure.	Procedure: Endobronchial Biopsy of Airway Epithelium; During standard post-transplantation bronchoscopies, participants in this study will undergo an endobronchial biopsy of the airway epithelium for each donor lung.; Other Names: Airway Biopsy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Subjects Needing Airway Stent Placement as Determined by Transbronchial Lung Biopsy.	Airways with stenosis refractory to serial balloon dilation x 3, or at risk for acute obstruction due to stenosis were treated with airway stents.	12 months
Number of Subjects Experiencing Acute Cellular Rejection as Determined by Transbronchial Lung Biopsy	Pathologic specimens will be examined for the presence of acute cellular rejection.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects With Development of Clinically Significant Airway Stenosis		12 months
Number of Subjects Receiving Balloon Bronchoplasty for Management of Stenosis		12 months
Number of Subjects With Development of Clinically Significant Lung Infection	As defined by initiation of antimicrobials to treat the suspected organism.	12 months
Number of Subjects With Development of Bronchitis Obliterans Syndrome		12 months

Other Outcome Measures

Outcome Measure	Time Frame
Bronchial Epithelial Gene Expression	12 months

Collaborators and Investigators

• Sponsor: Duke University
• Investigators: Principal Investigator: Scott Shofer, Duke Health

Publications and helpful links

General Publications

• Kraft BD, Mahmood K, Harlan NP, Hartwig MG, Snyder LD, Suliman HB, Shofer SL. Hyperbaric oxygen therapy to prevent central airway stenosis after lung transplantation. J Heart Lung Transplant. 2021 Apr;40(4):269-278. doi: 10.1016/j.healun.2021.01.008. Epub 2021 Jan 15.

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2015
• Primary Completion (Actual): September 30, 2018
• Study Completion (Actual): September 30, 2018

Study Registration Dates

• First Submitted: February 10, 2015
• First Submitted That Met QC Criteria: February 10, 2015
• First Posted (Estimated): February 16, 2015

Study Record Updates

• Last Update Posted (Estimated): November 17, 2023
• Last Update Submitted That Met QC Criteria: November 15, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Bronchoscopy; Hyperbaric Oxygen; Lung Transplantation; Hyperbaric Oxygen Therapy; Central Airway Stenosis; Airway Exudative Plaques; Post-Lung Transplantation; Airway Ischemia; Endobronchial Biopsy
• Additional Relevant MeSH Terms: Pathological Conditions, Anatomical; Constriction, Pathologic
• Other Study ID Numbers: Pro00055849