Lung Transplant Infection
Conditions
Keywords
Chronic lung allograft dysfunction, Community-acquired respiratory viral infection
Brief summary
The purpose of this study is to determine if the use of inhaled beclomethasone after a community-acquired respiratory viral infection in a lung transplant recipient decreases the risk of the subsequent development of chronic lung allograft dysfunction.
Detailed description
Community-acquired respiratory viral (CARV) infections after lung transplantation are associated with an increased risk for the development of chronic lung allograft dysfunction (CLAD) after lung transplantation. The exact mechanisms whereby CARV infections increase this risk are unknown. We propose that viral infection results in airway epithelial cell injury and the expression of injury-response genes that provide signals that initiate immunologic and non-immunologic pathways that result in the airway remodeling characteristic of obliterative bronchiolitis, the predominant pathology of CLAD. Systemic and inhaled corticosteroids are frequently used as anti-inflammatory agents to treat the peribronchiolar inflammation seen in viral bronchiolitis. Beneficial effects from corticosteroids have been reported, but this has not been demonstrated in lung transplant recipients. The aim of this single center, randomized, double blind, placebo controlled study is to evaluate the short and long term effects of a 6 month course of inhaled beclomethasone on adult lung transplant recipients with CARV infection.
Interventions
DRUGInhaled beclomethasone
Inhaled steroid that may decrease airway inflammation and the risk of chronic rejection
DRUGPlacebo
Placebo will serve as a control treatment
Sponsors
Washington University School of Medicine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adult (≥ 18 years old) * Single, bilateral, or heart-lung transplant recipient * Confirmed infection with a community-acquired respiratory virus including: adenovirus, coronavirus, influenza A or B, respiratory syncytial virus (RSV), parainfluenza virus (PiV), human metapneumovirus (hMPV), and rhinovirus * At least 6 months post-transplant, with completion of 6 month bronchoscopy if indicated * Able and willing to give written informed consent and comply with study procedures (e.g. testing, treatment)
Exclusion criteria
* BOS Stage 3 * Requirement for mechanical ventilation at study entry * Use of inhaled steroids at the time of CARV infection * Any condition that in the investigator's opinion would preclude the patient's participation in a clinical trial * Lack of available spirometric data to establish a baseline forced expiratory volume in 1 second and/or forced vital capacity * Pregnancy * Current participation in another interventional clinical trial
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Participants Free From New or Progressive Chronic Lung Allograft Dysfunction | 180 days |
| Death | 180 days |
Secondary
| Measure | Time frame |
|---|---|
| Acute Rejection | 180 days |
| Lymphocytic Bronchiolitis | 180 days |
| Donor-specific Antibodies | 180 days |
| Chronic Lung Allograft Dysfunction | 180 days |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Inhaled Beclomethasone Inhaled beclomethasone 320 mcg twice daily for 180 days.
Inhaled beclomethasone: Inhaled steroid that may decrease airway inflammation and the risk of chronic rejection | 7 |
| Placebo Inhaled placebo twice daily for 180 days.
Placebo: Placebo will serve as a control treatment | 8 |
| Total | 15 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Placebo | Total | Inhaled Beclomethasone |
|---|---|---|---|
| Age, Continuous | 62 years STANDARD_DEVIATION 6.6 | 57.1 years STANDARD_DEVIATION 15.3 | 51.6 years STANDARD_DEVIATION 20.7 |
| Bronchiolitis Obliterans Syndrome Stage BOS Stage 0 or 0p (Forced expiratory volume in 1 second is at least 81% of baseline) | 6 participants | 13 participants | 7 participants |
| Bronchiolitis Obliterans Syndrome Stage BOS Stage 1 or 2 (Forced expiratory volume in 1 second is between 51-80% of baseline) | 2 participants | 2 participants | 0 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 7 Participants | 14 Participants | 7 Participants |
| Sex: Female, Male Female | 5 Participants | 8 Participants | 3 Participants |
| Sex: Female, Male Male | 3 Participants | 7 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 7 | 0 / 8 |
| other Total, other adverse events | 7 / 7 | 8 / 8 |
| serious Total, serious adverse events | 3 / 7 | 5 / 8 |
Outcome results
Primary
Death
Time frame: 180 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Inhaled Beclomethasone | Death | 0 Participants |
| Placebo | Death | 0 Participants |
Primary
Number of Participants Free From New or Progressive Chronic Lung Allograft Dysfunction
Time frame: 180 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Inhaled Beclomethasone | Number of Participants Free From New or Progressive Chronic Lung Allograft Dysfunction | 2 Participants |
| Placebo | Number of Participants Free From New or Progressive Chronic Lung Allograft Dysfunction | 4 Participants |
Secondary
Acute Rejection
Time frame: 180 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Inhaled Beclomethasone | Acute Rejection | 1 Participants |
| Placebo | Acute Rejection | 0 Participants |
Secondary
Chronic Lung Allograft Dysfunction
Time frame: 180 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Inhaled Beclomethasone | Chronic Lung Allograft Dysfunction | 2 Participants |
| Placebo | Chronic Lung Allograft Dysfunction | 3 Participants |
Secondary
Donor-specific Antibodies
Time frame: 180 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Inhaled Beclomethasone | Donor-specific Antibodies | 0 Participants |
| Placebo | Donor-specific Antibodies | 0 Participants |
Secondary
Lymphocytic Bronchiolitis
Time frame: 180 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Inhaled Beclomethasone | Lymphocytic Bronchiolitis | 0 Participants |
| Placebo | Lymphocytic Bronchiolitis | 1 Participants |