Aztreonam Lysine for Inhalation (AZLI) in the Treatment of Early Bronchiolitis Obliterans Syndrome (BOS) After Lung Transplantation
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 30
- 试验地点
- 2
- 主要终点
- Change in Pulmonary Function, as Measured by Serial Forced Expiratory Volume in 1 Second (FEV1) on Spirometry
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Aztreonam Lysine for Inhalation (AZLI)
Patients to received Aztreonam Lysine(AZLI)
干预措施: Status Post Lung Transplant (Procedure)
Aztreonam Lysine for Inhalation (AZLI)
Patients to received Aztreonam Lysine(AZLI)
干预措施: Aztreonam Lysine for Inhalation (AZLI) (Drug)
结局指标
主要结局
Change in Pulmonary Function, as Measured by Serial Forced Expiratory Volume in 1 Second (FEV1) on Spirometry
时间窗: Baseline, month 5
Within-subject change to absolute FEV1 month 5 vs 0.
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
时间窗: 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).
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.
时间窗: 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).
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.
时间窗: 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
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
时间窗: 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).
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
时间窗: 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
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.
时间窗: 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).
次要结局
- 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))
- Change in FEV1 Off AZLI Therapy(At Study Months 2 and 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)
- Change in HRQOL Off AZLI Therapy.(At study months 2 or 4)