A Retrospective Chart Review Study of Patients With CLAD-BOS Post Lung Transplantation

NCT06503770 | Completed Results

• 1 other identifier: Z8000N01
• Study Type: observational
• Target: 284
• Locations: 3 countries
• Sites: 6

Brief Summary

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.

Conditions

Bronchiolitis Obliterans Syndrome

Keywords

Chronic Lung Allograft Dysfunction; Bronchiolitis Obliterans Syndrome; Post-Lung Transplantation; Retrospective Chart Review

Outcome Measures

Primary Outcomes (2)

• Change Per Year in FEV1 Trajectory Starting From the Onset Date Through the End of the Post-diagnosis Period.

  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.

  From CLAD-BOS onset up to 3 years post-onset

• Change in FEV1 Trajectory Over Time Starting From the Onset Date Through the End of the Post-diagnosis Period.

  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.

  From CLAD-BOS onset up to 3 years post-onset

Secondary Outcomes (20)

• 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

Study Arms (1)

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.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

The study population included adult patients (aged ≥ 18) years who were recipients of a lung transplant and diagnosed with CLAD-BOS from the first of 01 January 2013 following transplantation.

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Zambon SpA: lead

Study Sites (6)

Cleveland Clinic Transplantation Center

Cleveland, Ohio, 44195, United States

Location

The Ohio State University

Columbus, Ohio, 43210, United States

Location

Baylor Scott and White Health Center for Advanced Heart and Lung Disease

Dallas, Texas, 75246, United States

Location

Universitaire Ziekenhuizen Leuven (UZ Leuven)

Leuven, Leuven, 3000, Belgium

Location

Hospital Universitario Reina Sofia

Córdoba, Andalusia, 14004, Spain

Location

Hospital Universitario Marques de Valdecilla (HUMV)

Santander, Cantabria, 39008, Spain

Location

MeSH Terms

Conditions

Bronchiolitis Obliterans Syndrome

Condition Hierarchy (Ancestors)

Organizing Pneumonia; Bronchiolitis Obliterans; Bronchiolitis; Bronchitis; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Graft vs Host Disease; Immune System Diseases

Limitations and Caveats

The population was obtained from participating sites, which may limit generalizability. However, the study was multicenter and multinational, with minimal inclusion and exclusion criteria applied. As a retrospective study, data completeness was dependent on the availability of the medical records. CLAD BOS diagnosis was clinician-determined, while onset dates were programmatically derived, potentially introducing limited misclassification. Median follow-up was shorter than planned.

Results Point of Contact

• Title: Paola Castellani, Chief Medical Officer & R&D Head
• Organization: Zambon SpA

clinicaltrials@zambongroup.com

+3902665241

Study Officials

• Paola Castellani, MD

  Zambon SpA

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: RETROSPECTIVE
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 8, 2024
• First Posted: July 16, 2024
• Study Start: June 27, 2024
• Primary Completion: April 9, 2025
• Study Completion: April 9, 2025
• Last Updated: September 1, 2026
• Results First Posted: September 1, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will not share

Locations

ES (2); US (3); BE (1)