Bronchiolitis Obliterans, Chronic Rejection of Lung Transplant, Decreased Immunologic Activity, Disorder Related to Lung Transplantation
Conditions
Keywords
case-control study, aerosolized liposomal cyclosporine A, bronchiolitis obliterans syndrome, Lung Transplantation, Lung function
Brief summary
This is a single-center pilot study to investigate the efficacy and safety of aerosolized liposomal cyclosporine A in the treatment of chronic rejection in lung transplant recipients with bronchiolitis obliterans syndrome (BOS). The primary objective is to evaluate the efficacy of liposomal cyclosporine A in the treatment of chronic rejection. Pulmonary function and changes in BOS grade are the primary end points.
Detailed description
This is a randomized single-center pilot study to investigate the efficacy and safety of aerosolized liposomal cyclosporine A (L-CsA) in the treatment of chronic rejection in lung transplant recipients with Grade 1 or 2 BOS. The primary endpoints will include: * Improvement or stabilization of pulmonary function test (FEV1) from baseline * Stabilization of histology (no deterioration from baseline) * Safety of the preparation The secondary endpoints will include: * Pharmacokinetics and distribution of CsA in blood - * Change in cytokine levels from BAL specimens.
Interventions
DRUGLiposomal aerosol cyclosporine
inhaled form of immune suppression
OTHERstandard immune suppression, oral
conventional drug Conventrional oral immune suppression as standard of care thus consists of tacrolimus, mycophenolate mofetil prednisone and rapamycin
Sponsors
University of Maryland, Baltimore
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Masking description
Open Label
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Chronic rejection 1. Bronchiolitis obliterans diagnosed by bronchiolitis obliterans syndrome and \> 20% decline from the individual patient's best FEV1 is observed 2. Recipient of a double or single lung transplant 3. Receiving immunosuppressive treatment according to institutional standards
Exclusion criteria
1. Active invasive bacterial, viral or fungal infection 2. Current mechanical ventilation 3. Pregnant or breast-feeding woman 4. Known hypersensitivity to cyclosporine A 5. Serum creatinine value of more than 265 μmol/L (3 mg/dL) or chronic dialysis 6. Receipt of an investigational drug as part of a clinical trial
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number Of Participants With Chronic Rejection Who Met Primary Combined End-point | approximately 1 year | Treatment failure defined as: BOS progression (\> 20% decline lung function), re-transplant, or death |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cytokine Analysis From BAL Fluid in Lung | baseline to approximately 1 year | Multiple cytokines were assessed as markers of lung inflammation that may be used in addition to biopsy data, collected per patient as clinically indicated during the follow-up interval. Values are reported as mean change from baseline in each group, per week |
| Overall Survival at 5 Years Follow-up | 5 years | Number of participants surviving at 5 year follow-up |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Liposomal Aerosol Cyclosporine Arm 1) Aerosol liposomal cyclosporine Open label randomized trial using experimental inhalational therapy with liposomal aerosol cyclosporine in addition to standard immune suppression (tacrolimus , mycophenolate mofetil and prednisone) for 6 month duration at inhalational doses (5mg and 10 mg bid), to be defined by transplant type respectively (single, double lung transplant )
Liposomal aerosol cyclosporine: inhaled form of immune suppression
standard immune suppression, oral: conventional drug | 11 |
| Conventional Oral Immune Suppression Arm 2) Standard immune suppression consisting of typical oral immune suppression for lung transplant recipients typically tacrolimus, mycophenolate mofetil and prednisone
standard immune suppression, oral: conventional drug | 10 |
| Total | 21 |
Baseline characteristics
| Characteristic | Liposomal Aerosol Cyclosporine | Total | Conventional Oral Immune Suppression |
|---|---|---|---|
| Age, Continuous | 59.1 years | 61.3 years | 63.8 years |
| 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 | 3 Participants | 5 Participants | 2 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 | 8 Participants | 16 Participants | 8 Participants |
| Region of Enrollment United States | 11 Participants | 21 Participants | 10 Participants |
| Sex: Female, Male Female | 5 Participants | 7 Participants | 2 Participants |
| Sex: Female, Male Male | 6 Participants | 14 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 6 / 11 | 10 / 10 |
| other Total, other adverse events | 11 / 11 | 10 / 10 |
| serious Total, serious adverse events | 8 / 11 | 8 / 10 |
Outcome results
Primary
Number Of Participants With Chronic Rejection Who Met Primary Combined End-point
Treatment failure defined as: BOS progression (\> 20% decline lung function), re-transplant, or death
Time frame: approximately 1 year
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Liposomal Aerosol Cyclosporine | Number Of Participants With Chronic Rejection Who Met Primary Combined End-point | 2 Participants |
| Conventional Oral Immune Suppression | Number Of Participants With Chronic Rejection Who Met Primary Combined End-point | 5 Participants |
p-value: 0.03Log Rank
Secondary
Cytokine Analysis From BAL Fluid in Lung
Multiple cytokines were assessed as markers of lung inflammation that may be used in addition to biopsy data, collected per patient as clinically indicated during the follow-up interval. Values are reported as mean change from baseline in each group, per week
Time frame: baseline to approximately 1 year
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Liposomal Aerosol Cyclosporine | Cytokine Analysis From BAL Fluid in Lung | lL-1beta | -2 pg/mL |
| Liposomal Aerosol Cyclosporine | Cytokine Analysis From BAL Fluid in Lung | IL-6 | -2.0 pg/mL |
| Liposomal Aerosol Cyclosporine | Cytokine Analysis From BAL Fluid in Lung | IL-8 | 13.6 pg/mL |
| Liposomal Aerosol Cyclosporine | Cytokine Analysis From BAL Fluid in Lung | IL-10 | 0.1 pg/mL |
| Liposomal Aerosol Cyclosporine | Cytokine Analysis From BAL Fluid in Lung | IL-17 | 0.4 pg/mL |
| Liposomal Aerosol Cyclosporine | Cytokine Analysis From BAL Fluid in Lung | TNF-alpha | 1.9 pg/mL |
| Liposomal Aerosol Cyclosporine | Cytokine Analysis From BAL Fluid in Lung | IFN-gamma | 0.5 pg/mL |
| Liposomal Aerosol Cyclosporine | Cytokine Analysis From BAL Fluid in Lung | IL-2 | -0.9 pg/mL |
| Conventional Oral Immune Suppression | Cytokine Analysis From BAL Fluid in Lung | IL-10 | 0.1 pg/mL |
| Conventional Oral Immune Suppression | Cytokine Analysis From BAL Fluid in Lung | lL-1beta | 3.3 pg/mL |
| Conventional Oral Immune Suppression | Cytokine Analysis From BAL Fluid in Lung | IL-2 | -0.3 pg/mL |
| Conventional Oral Immune Suppression | Cytokine Analysis From BAL Fluid in Lung | TNF-alpha | -1.7 pg/mL |
| Conventional Oral Immune Suppression | Cytokine Analysis From BAL Fluid in Lung | IL-6 | 6.3 pg/mL |
| Conventional Oral Immune Suppression | Cytokine Analysis From BAL Fluid in Lung | IL-17 | 0.1 pg/mL |
| Conventional Oral Immune Suppression | Cytokine Analysis From BAL Fluid in Lung | IL-8 | 37.5 pg/mL |
| Conventional Oral Immune Suppression | Cytokine Analysis From BAL Fluid in Lung | IFN-gamma | 0 pg/mL |
Secondary
Overall Survival at 5 Years Follow-up
Number of participants surviving at 5 year follow-up
Time frame: 5 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Liposomal Aerosol Cyclosporine | Overall Survival at 5 Years Follow-up | 5 Participants |
| Conventional Oral Immune Suppression | Overall Survival at 5 Years Follow-up | 0 Participants |