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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Gilead Sciences
Information provided by (Responsible Party):
Duke University
ClinicalTrials.gov Identifier:
NCT01469364
First received: November 8, 2011
Last updated: August 15, 2014
Last verified: August 2014
  Purpose

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.


Condition Intervention Phase
Complication of Transplanted Lung
Drug: Aztreonam Lysine for Inhalation (AZLI)
Procedure: Status Post Lung Transplant
Phase 4

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by Duke University:

Primary Outcome Measures:
  • 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 Health-Related Quality of Life (HRQOL), as measured by the SF-36 and St. George Respiratory Questionnaire [ Time Frame: At the end of study months 1 and 5, on AZLI therapy, as compared to study month 0 (baseline) ] [ Designated as safety issue: Yes ]
  • Safety Endpoints [ Time Frame: 1 month and 5 month ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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)

  • 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).


Estimated Enrollment: 30
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)
Arms Assigned Interventions
Experimental: Aztreonam Lysine for Inhalation (AZLI)
Patients to received 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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01469364

Locations
United States, California
David Geffen School of Medicine at UCLA
Los Angeles, California, United States, 90095
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
Sponsors and Collaborators
Duke University
Gilead Sciences
Investigators
Principal Investigator: Scott Palmer, MD Duke University
  More Information

Publications:

Responsible Party: Duke University
ClinicalTrials.gov Identifier: NCT01469364     History of Changes
Other Study ID Numbers: Pro00030559, Gilead Sciences, Inc, Pro00030191
Study First Received: November 8, 2011
Last Updated: August 15, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Duke University:
Lung Transplant
Lung Transplant Recipient

Additional relevant MeSH terms:
Lung Diseases
Lung Diseases, Obstructive
Bronchiolitis
Bronchiolitis Obliterans
Bronchial Diseases
Bronchitis
Respiratory Tract Diseases
Respiratory Tract Infections
Aztreonam
Anti-Bacterial Agents
Anti-Infective Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 27, 2014