A Retrospective Chart Review Study of Patients With Chronic Lung Allograft Dysfunction-Bronchiolitis Obliterans Syndrome (CLAD-BOS) Post Lung Transplantation
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- Zambon SpA
- 入组人数
- 284
- 试验地点
- 11
- 主要终点
- To evaluate the FEV1 trajectory of patients diagnosed with CLAD-BOS
研究概览
简要总结
The Primary Objective of this study was to evaluate the FEV1 trajectory of patients diagnosed with CLAD-BOS.
The Secondary Objectives of this study were:
- To describe demographics of patients diagnosed with CLAD-BOS
- To describe clinical characteristics following lung transplantation for patients diagnosed with CLAD-BOS
- To evaluate the trajectory of other relevant spirometry parameters (ie, FVC, FEV1/FVC, FEF25-75%)
- To evaluate the OS of patients diagnosed with CLAD-BOS
- To evaluate the time to first CLAD-BOS progression
- To evaluate the cumulative incidence of CLAD-BOS progression
- To evaluate the rate of hospitalization due to respiratory failure after CLAD-BOS onset
- To evaluate the incidence of concomitant respiratory disease
- To evaluate the incidence of concomitant non-respiratory disease
- To describe the use of concomitant treatments and procedures for CLAD-BOS.
详细描述
This was a retrospective, multinational, multicenter, observational chart review study conducted in adult patients with clinically diagnosed chronic lung allograft dysfunction-bronchiolitis obliterans syndrome (CLAD-BOS) following lung transplantation.
All data were retrospectively collected from existing patient medical records; no interventions were applied as part of the study, and no protocol-mandated patient assessments or follow-up visits were required.
The observational period for each patient encompassed multiple time points relevant to the development and progression of CLAD-BOS. Patients were identified within a CLAD-BOS diagnosis window spanning from 01 January 2013 through the most recent data available at the participating study sites.
The index date was defined as the date of clinician diagnosis of CLAD-BOS as documented in the medical record. Spirometry parameters at diagnosis were based on the spirometry assessment closest to the diagnosis date.
Personal best FEV1 was defined as the highest post-transplant FEV1 value documented prior to the diagnosis of CLAD-BOS, based on available spirometry measurements collected after lung transplantation and before diagnosis. The personal best FEV1 date corresponded to the time point at which this best post-transplant FEV1 value was identified. The personal best post-transplant FEV1 value was defined as the mean of the 2 best post-transplant FEV1 measurements taken at least 3 weeks apart, with the date being that of the first value.
研究设计
- 研究类型
- Observational
- 观察模型
- Other
- 时间视角
- Retrospective
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 patients ≥ 18 years of age on the date of CLAD-BOS diagnosis
- •Patients with a CLAD-BOS clinician diagnosis from as early as 01 January 2013
- •Patients with CLAD-BOS clinician diagnosis made at least 12 months after lung transplant
- •Patients received at least basic maintenance regimen of immunosuppressive agents including tacrolimus, a second agent such as but not limited to mycophenolate mofetil or azathioprine (or other anti-proliferative agent), and a systemic corticosteroid such as prednisone as third agent for at least 1 month before the index date. As long as the basic maintenance regimen is maintained for the abovementioned period, patients will still be considered eligible for the study even if they are receiving other immunosuppressive agents in addition to the basic maintenance regimen.
排除标准
- •Patients with severe concomitant disease at the time of index date, which according to physician's judgment, can interfere with CLAD-BOS progression and mortality (e.g., malignancies, severe chronic diseases)
- •Patients who have been exposed to any investigational medical products in the 4 weeks prior to index date or during the post-diagnosis period
- •Patients with confirmed other CLAD phenotype (e.g., restrictive allograft syndrome) according to physician's judgment.
研究组 & 干预措施
CLAD-BOS Cohort
Adult patients with clinically diagnosed chronic lung allograft dysfunction-bronchiolitis obliterans syndrome (CLAD-BOS) following lung transplantation, included in a retrospective observational chart review study. No study-specific interventions were administered.
结局指标
主要结局
To evaluate the FEV1 trajectory of patients diagnosed with CLAD-BOS
时间窗: Up to 12 years
Change in FEV1 trajectory over time
Change Per Year in FEV1 Trajectory Starting From the Onset Date Through the End of the Post-diagnosis Period.
时间窗: From CLAD-BOS onset up to 3 years post-onset
CLAD-BOS onset was defined as the first occurrence of a forced expiratory volume in 1 second (FEV1) value ≤80% of the patient's post-transplant best FEV1, confirmed by a subsequent measurement ≤80% at least 3 months later, as documented in the medical records. The personal best FEV1 was defined as the mean of the two highest post-transplant FEV1 measurements obtained at least 3 weeks apart, derived from post-transplant spirometry data or identified in clinical records according to physician judgment. The FEV1 value at CLAD-BOS onset served as the baseline for the analysis. Repeated post-onset spirometry measurements collected during routine clinical practice were analyzed using a linear mixed-effects model with random subject-specific effects. Results are reported as model-based estimated mean changes from baseline in FEV1 per year. The reported mean values represent estimates derived from the statistical model.
Change in FEV1 Trajectory Over Time Starting From the Onset Date Through the End of the Post-diagnosis Period.
时间窗: From CLAD-BOS onset up to 3 years post-onset
CLAD-BOS onset was defined as the first occurrence of a forced expiratory volume in 1 second (FEV1) value ≤80% of the patient's post-transplant best FEV1, confirmed by a subsequent measurement ≤80% at least 3 months later, as documented in the medical records. The personal best FEV1 was defined as the mean of the two highest post-transplant FEV1 measurements obtained at least 3 weeks apart, derived from post-transplant spirometry data or identified in clinical records according to physician judgment. The FEV1 value at CLAD-BOS onset served as the baseline for the analysis. Repeated post-onset spirometry measurements collected during routine clinical practice were analyzed using a linear mixed-effects model with random subject-specific effects. Results are reported as model-based estimated mean changes from baseline in FEV1 at prespecified time points after onset (1, 2, and 3 years). The reported mean values represent estimates derived from the statistical model.
次要结局
- Age at Transplant(At transplant date)
- Sex at Transplant(At transplant date)
- Race(At transplant date)
- Number of Participants With Pre-transplant Medical History and Lung Transplant History(Up to transplant date)
- Time From Lung Transplantation to CLAD-BOS Onset(From transplant date to onset date)
- Number of Participants With Clinical Characteristics Following Lung Transplantation (Acute Rejection Events, Presence of Lung Opacities, and Signs, Symptoms, or Other Clinical Records)(From lung transplantation until last date of data available or death. Specifically, from transplantation to CLAD-BOS onset, a median of 40.5 (max 227) months; from CLAD-BOS onset to last data available or death a median of 38.6 (max 173) months)
- Percentage of Participants by Donor-specific Antibodies Results(From lung transplantation until last date of data available or death. Specifically, from transplantation to CLAD-BOS onset, a median of 40.5 (max 227) months; from CLAD-BOS onset to last data available or death a median of 38.6 (max 173) months)
- Total Lung Capacity (Plethysmography)(From lung transplantation until last date of data available or death. Specifically, from transplantation to CLAD-BOS onset, a median of 40.5 (max 227) months; from CLAD-BOS onset to last data available or death a median of 38.6 (max 173) months)
- Change Per Year in FVC Trajectory(From CLAD-BOS onset up to 3 years post-onset)
- Change in FVC Trajectory Over Time(From CLAD-BOS onset up to 3 years post-onset)
- Change Per Year in FEV1/FVC Trajectory(From CLAD-BOS onset up to 3 years post-onset)
- Change in FEV1/FVC Trajectory Over Time(From CLAD-BOS onset up to 3 years post-onset)
- Change in FEF25-75% Trajectory Over Time(From CLAD-BOS onset up to 3 years post-onset)
- Overall Survival (OS) From CLAD-BOS Onset(From CLAD-BOS onset through death, up to 120 months)
- Time to First CLAD-BOS Progression(From CLAD-BOS onset through death (median follow up time 38.6 months))
- Cumulative Number of CLAD-BOS Progression Events Per Patient(From CLAD-BOS onset to last data available or death a median of 38.6 (max 173) months)
- Hospitalization Rate Due to Respiratory Failure(From CLAD-BOS onset to last data available or death a median of 38.6 (max 173) months)
- Number of Participants With Newly Diagnosed Cases of Concomitant Respiratory Diseases(From CLAD-BOS onset to last data available or death a median of 38.6 (max 173) months)
- Concomitant Treatments and Procedures for CLAD-BOS Starting From the Post-transplant Date Through the End of the Post-diagnosis Period(From lung transplantation until last date of data available or death. Specifically, from transplantation to CLAD-BOS onset, a median of 40.5 (max 227) months; from CLAD-BOS onset to last data available or death a median of 38.6 (max 173) months)
- Number of Participants With Newly Diagnosed Cases of Concomitant Non-respiratory Diseases(From CLAD-BOS onset to last data available or death a median of 38.6 (max 173) months)