Aztreonam Lysine for Inhalation (AZLI) in the Treatment of Early Bronchiolitis Obliterans Syndrome (BOS) After Lung Transplantation

Safety Study of Aztreonam Lysine for Inhalation (AZLI) in the Treatment of Early Bronchiolitis Obliterans Syndrome (BOS)

Sponsors

Lead sponsor: Duke University

Collaborator: Gilead Sciences

Source Duke University
Brief Summary

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 diagnosed 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.

Detailed Description

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.

Overall Status Completed
Start Date March 2013
Completion Date April 2015
Primary Completion Date March 2015
Phase Phase 4
Study Type Interventional
Primary Outcome
Measure Time Frame
Change in Pulmonary Function, as Measured by Serial Forced Expiratory Volume in 1 Second (FEV1) on Spirometry Baseline, month 1
Change in Pulmonary Function, as Measured by Serial Forced Expiratory Volume in 1 Second (FEV1) on Spirometry Baseline, month 5
Change in Global Health Related Quality of Life, Measured by Serially Self-administered Short Form 36 Health Survey Questionnaire (SF-36) at Baseline (Prior to AZLI First Dose) and During AZLI Therapy at Month 1 Baseline, month 1
Change in Global Health Related Quality of Life, Measured by Serially Self-administered Short Form 36 Health Survey Questionnaire (SF-36) at Baseline (Prior to AZLI First Dose) and During AZLI Therapy at Month 1 and Month 5. Baseline, month 5
Change in Respiratory-specific Health Related Quality of Life, Measured by Serially Self Administered St. George's Respiratory Questionnaire (SGRQ) at Baseline (Prior to AZLI First Dose) and During AZLI Therapy at Month 1 Baseline, month 1
Change in Respiratory-specific Health Related Quality of Life, Measured by Serially Self Administered St. George's Respiratory Questionnaire (SGRQ) at Baseline (Prior to AZLI First Dose) and During AZLI Therapy at Month 5. Baseline, month 5
Change in Pulmonary Function, as Measured by Serial Forced Expiratory Flow (FEF25-75) on Spirometry at Baseline (Prior to AZLI First Dose) and During AZLI Therapy at Month 5. Baseline, month 5
Change in Pulmonary Function, as Measured by Serial Forced Expiratory Flow (FEF25-75) on Spirometry at Baseline (Prior to AZLI First Dose) and During AZLI Therapy at Month 1 Baseline, month 1
Secondary Outcome
Measure Time Frame
Change in FEV1 Off AZLI Therapy At Study Months 2 and 4
Change in HRQOL Off AZLI Therapy. At study months 2 or 4
Among Patients Colonized With Pseudomonas Aeruginosa, Change in Infection Burden as Measured by the Culture Final Report (0,1+, 2+, 3+, 4+) of in Pseudomonas Aeruginosa Sputum or Bronchoalveolar Fluid. Baseline, month 1
Bronchoalveolar Lavage Fluid (BALF) Neutrophilia After Treatment, When Performed as Part of Clinical Care (SOC). Baseline - defined as a within 90 days of enrollment and After Treatment (5 months)
Enrollment 30
Condition
Intervention

Intervention type: Drug

Intervention name: Aztreonam Lysine for Inhalation (AZLI)

Description: 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)

Arm group label: Aztreonam Lysine for Inhalation (AZLI)

Intervention type: Procedure

Intervention name: Status Post Lung Transplant

Description: 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.

Arm group label: Aztreonam Lysine for Inhalation (AZLI)

Other name: Standard Post Lung Transplant Care

Eligibility

Criteria:

Inclusion Criteria:

- Adult (18 or older at the time of transplant) male or female

- Cadaveric first lung transplant recipient, single or bilateral; or multi-organ lung transplant recipient.

- Current FEV1 66-80% of posttransplant baseline FEV1, and meets all criteria for BOS 1 as defined by the International Society of Heart and Lung Transplantation.

- Onset of BOS 1 within twelve months of screening

Exclusion Criteria:

- Known allergy to aztreonam

- Retransplant

- Pediatric patients

- Live lobar transplant recipients

- Inability to provide informed consent.

- Patients with advanced BOS (grades 2,3) or established BOS >6 months

- Pregnant Women

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Overall Official
Last Name Role Affiliation
Scott Palmer, MD Principal Investigator Duke University
Location
facility
David Geffen School of Medicine at UCLA | Los Angeles, California, 90095, United States
Duke University Medical Center | Durham, North Carolina, 27710, United States
Location Countries

United States

Verification Date

December 2015

Responsible Party

Responsible party type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 1
Arm Group

Arm group label: Aztreonam Lysine for Inhalation (AZLI)

Arm group type: Experimental

Description: Patients to received Aztreonam Lysine(AZLI)

Acronym AZLI
Study Design Info

Allocation: N/A

Intervention model: Single Group Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Source: ClinicalTrials.gov