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

December 22, 2015 updated by: Duke University

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

30

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Los Angeles, California, United States, 90095
        • David Geffen School of Medicine at UCLA
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Duke University Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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)
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 Names:
  • Standard Post Lung Transplant Care

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Pulmonary Function, as Measured by Serial Forced Expiratory Volume in 1 Second (FEV1) on Spirometry
Time Frame: Baseline, month 1
Within-subject change to absolute FEV1 month 1 vs. 0. FEV1 was measured 14-35 days after the start of months 1 AZLI courses and compared to study month 0 (baseline/prior to 1st dose).
Baseline, month 1
Change in Pulmonary Function, as Measured by Serial Forced Expiratory Volume in 1 Second (FEV1) on Spirometry
Time Frame: Baseline, month 5
Within-subject change to absolute FEV1 month 5 vs 0.
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
Time Frame: Baseline, month 1
The SF-36 is a commonly used, well validated measure of global health related quality of life. The survey was self-administered. There are 8 subscales which combine to form a Physical Component Score (PCS) and a Mental Component Score (MCS). We analyzed within subject changes to the PCS and MCS at month 1 vs. 0. MCS and PCS scores are relative to a US population mean of 50. The higher the score, the better one perceives his quality of life. A change in score of 4 points or more is considered clinically meaningful. Scores represent Median Absolute Difference. The SF-36 was completed 14-35 days after the start of months 1 AZLI courses and compared to study month 0 (baseline/prior to 1st dose).
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.
Time Frame: Baseline, month 5
The SF-36 is a commonly used, well validated measure of global health related quality of life. The survey was self-administered. There are 8 subscales which combine to form a Physical Component Score (PCS) and a Mental Component Score (MCS). We analyzed within subject changes to the PCS and MCS at month 5 vs 0. MCS and PCS scores are relative to a US population mean of 50. The higher the score, the better one perceives his quality of life. A change in score of 4 points or more is considered clinically meaningful. Scores represent Median Absolute Difference. The SF-36 was completed 14-35 days after the start of months 1 and 5 AZLI courses and compared to study month 0 (baseline/prior to 1st dose).
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
Time Frame: Baseline, month 1
The SRGQ measures activities, symptoms, and impacts of living with a pulmonary condition. We analyzed the change to the within-subject Total score month 1 vs. 0. Total score ranges from 0-100 with a smaller value representing better respiratory-specific QOL. A change in score of 4 points or more is considered clinically meaningful. Scores represent Median Absolute Difference in the Total Score. The SGRQ was completed 14-35 days after the start of months 1 AZLI courses and compared to study month 0 (baseline/prior to 1st dose).
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.
Time Frame: Baseline, month 5
The SRGQ measures activities, symptoms, and impacts of living with a pulmonary condition. We analyzed the change to the within-subject Total score month 5 vs 0. Total score ranges from 0-100 with a smaller value representing better respiratory-specific QOL. A change in score of 4 points or more is considered clinically meaningful. Scores represent Median Absolute Difference in theTotal Score. The SGRQ was completed 14-35 days after the start of month 5 AZLI courses and compared to study month 0 (baseline/prior to 1st dose).
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.
Time Frame: Baseline, month 5
Within-subject change to absolute FEF 25-75 month 5 vs 0. FEF 25-75 was measured 14-35 days after the start of months 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
Time Frame: Baseline, month 1
Within-subject change to absolute FEF 25-75 month 1 vs. 0. FEF 25-75 was measured 14-35 days after the start of months 1
Baseline, month 1

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in FEV1 Off AZLI Therapy
Time Frame: At Study Months 2 and 4
This will be compared to study month 0 (baseline, when obtained as standard of care (SOC).
At Study Months 2 and 4
Change in HRQOL Off AZLI Therapy.
Time Frame: At study months 2 or 4
This will be compared to study month 0 (baseline), when obtained at standard of care visit (SOC)
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.
Time Frame: Baseline, month 1
Microbiology data was collected when performed for SOC purposes on BAL or sputum samples. Baseline and 1 month value represents the culture final report value (0,1+, 2+, 3+, 4+) of Pseudomonas aeruginosa. A value of zero represents no Pseudomonas aeruginosa sputum or bronchoalveolar fluid. A value of 4 represents high amounts of Pseudomonas aeruginosa sputum or bronchoalveolar fluid.
Baseline, month 1
Bronchoalveolar Lavage Fluid (BALF) Neutrophilia After Treatment, When Performed as Part of Clinical Care (SOC).
Time Frame: Baseline - defined as a within 90 days of enrollment and After Treatment (5 months)
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 90 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).
Baseline - defined as a within 90 days of enrollment and After Treatment (5 months)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Duke University

Collaborators

Gilead Sciences

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2013

Primary Completion (ACTUAL)

March 1, 2015

Study Completion (ACTUAL)

April 1, 2015

Study Registration Dates

First Submitted

November 8, 2011

First Submitted That Met QC Criteria

November 9, 2011

First Posted (ESTIMATE)

November 10, 2011

Study Record Updates

Last Update Posted (ESTIMATE)

January 29, 2016

Last Update Submitted That Met QC Criteria

December 22, 2015

Last Verified

December 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Pro00030559
  • Gilead Sciences, Inc (OTHER: Gileand Sciences, Inc)
  • Pro00030191 (OTHER: Duke Site Protocol Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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