Safety Study of Aztreonam Lysine for Inhalation (AZLI) in the Treatment of Early Bronchiolitis Obliterans Syndrome (BOS)
This study is a pilot two- center study to determine if aztreonam lysine for inhalation AZLI can be safely and self-administered in lung transplant recipients with newly diagnosised bronchiolitis obliterans syndrome, grade 1 (BOS) and obtain pilot data regarding its effect on lung function in order to appropriately design and power a larger multicenter randomized study.
The hypothesis is that AZLI is a safe and effective treatment for declining lung function in lung transplant recipients with early stage BOS.
Complication of Transplanted Lung
Drug: Aztreonam Lysine for Inhalation (AZLI)
Procedure: Status Post Lung Transplant
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Aztreonam Lysine for Inhalation (AZLI) in the Treatment of Early Bronchiolitis Obliterans Syndrome (BOS) After Lung Transplantation|
- Change in pulmonary function, as measured by FEV1 and FEF 25-75 on spirometry, on AZLI therapy. [ Time Frame: As compared to study month 0 (baseline) at study Months 1 and 5 after intermittent therapy ] [ Designated as safety issue: Yes ]
FEV1 will be used primarily to assess the safety of therapy, but results will also be compared to historical data to assess the potential efficacy of treatment in BOS, matched to type of transplant (e.g. single or bilateral).
Change in Health-Related Quality of Life (HRQOL), as measured by the SF-36 and St. George Respiratory Questionnaire, at the end of study months 1 and 5, on AZLI therapy, as compared to study month 0 (baseline).
- Change in FEV1 off AZLI therapy [ Time Frame: At Study Months 2 and 4 ] [ Designated as safety issue: Yes ]This will be compared to study month 0 (baseline, when obtained as standard of care (SOC).
- Change in HRQOL off AZLI therapy. [ Time Frame: At study months 2 or 4 ] [ Designated as safety issue: Yes ]This will be compared to study month 0 (baseline), when obtained at standard of care visit (SOC)
- Change in HRQOL off AZLI therapy. [ Time Frame: at study months 2 or 4 ] [ Designated as safety issue: No ]This will be compared to study month 0 (baseline).
- Among patients colonized with Pseudomonas aeruginosa, change in infection burden as measured by the culture final report (1+, 2+, 3+, 4+) of Pseudomonas aeruginosa in sputum or bronchoalveolar fluid. [ Time Frame: at the end of study month 5 ] [ Designated as safety issue: Yes ]This will be compared to study month 0 (baseline)
- Bronchoalveolar lavage fluid (BALF) neutrophilia after treatment, when performed as part of clinical care (SOC). [ Time Frame: Baseline and After Treatment ] [ Designated as safety issue: Yes ]The study team is measuring the change in neutrophils AFTER treatment. They will compare a SOC BAL taken after AZLI with the BAL taken within 30 days of AZLI initiation (pre or baseline measure). The post AZLI BAL measurement time range is 15 days after first course of AZLI up to last day of the 3rd and final course of AZLI (over a period of 5 consecutive months).
|Study Start Date:||March 2013|
|Estimated Study Completion Date:||December 2015|
|Estimated Primary Completion Date:||March 2015 (Final data collection date for primary outcome measure)|
Experimental: Aztreonam Lysine for Inhalation (AZLI)
Patients to recieved Aztreonam Lysine(AZLI)
Drug: Aztreonam Lysine for Inhalation (AZLI)
The intervention will involve open label treatment with AZLI inhaled 75mg TID self-administered intermittently for 28 days on study drug and 28 days off study drug over a study period of 5 consecutive months (on/off/on/off/on AZLI)
Other Name: Aztreonam Lysine for Inhalation (AZLI)Procedure: Status Post Lung Transplant
Bronchoscopy, pulmonary function testing, and laboratory testing will be performed on a regular basis during study enrollment consistent with each center's usual standard clinical care.
Other Name: Standard Post Lung Transplant Care
Lung transplantation is increasingly employed as a therapy for patients with advanced lung disease including cystic fibrosis, idiopathic pulmonary fibrosis or emphysema. Despite significant short-term improvements in life quality and measures of lung function after lung transplantation, long-term outcomes are disappointing primarily due to the development of a condition of airway fibrosis known as bronchiolitis obliterans (BO). It is hypothesized that aztreonam lysine for inhalation (AZLI) is a safe and effective treatment for declining lung function in lung transplant recipients with early stage BOS. In order to test the hypothesis, the investigators seek to establish the safety of AZLI in a two-center cohort of 30 lung transplant recipients with BOS treated intermittently for 5 consecutive study months and determine if this treatment leads to improvement or stabilization of lung function. The intervention will involve open label treatment with AZLI, in addition to usual transplant care, administered for 3 intermittent courses, 28 days each, over a 5 month study period.. Bronchoscopy, pulmonary function testing, and laboratory testing will be performed on a regular basis during study enrollment consistent with each center's usual standard clinical care. Patients will have a baseline screening visit, one month and five month study visit.. The study will take two years to complete from the start of funding. After a start-up period of 2 months, a total of 30 patients will be enrolled over 12 months across the two centers (15 patients each at DUMC and UCLA). Each enrolled patient will complete 5 months of intermittent therapy, and complete baseline, month 1 and month 5 visits. Over the next 6 months the study database will be finalized, statistical analysis will for primary and secondary outcomes will be performed leading to the generation of either a study abstract or manuscript.
|Contact: Scott Palmer, MDfirstname.lastname@example.org|
|United States, California|
|David Geffen School of Medicine at UCLA||Not yet recruiting|
|Los Angeles, California, United States, 90095|
|Principal Investigator: John Belpreio, MD|
|United States, North Carolina|
|Duke University Medical Center||Recruiting|
|Durham, North Carolina, United States, 27710|
|Principal Investigator: Scott Palmer, MD|
|Principal Investigator:||Scott Palmer, MD||Duke University|