Eine retrospektive Chart-Review-Studie von Patienten mit chronischer Lungen-Allotransplantat-Dysfunktion-Bronchiolitis-obliterans-Syndrom (CLAD-BOS) nach Lungentransplantation
Studienübersicht
Status
Bedingungen
Detaillierte Beschreibung
Hierbei handelt es sich um eine retrospektive, multinationale, multizentrische Diagrammüberprüfungsstudie an erwachsenen Patienten mit klinisch diagnostiziertem CLAD-BOS nach Lungentransplantation. Alle Daten werden rückwirkend aus Patientenakten erfasst, beginnend mit dem Datum der Lungentransplantation bis zum letzten Datum der verfügbaren Daten. Daher werden im Rahmen dieser Studie keine Interventionen durchgeführt.
Der Beobachtungszeitraum für jeden Patienten reicht vom Datum der Lungentransplantation bis zum letzten Datum der verfügbaren Daten oder dem Tod, je nachdem, was früher eintritt, und umfasst die folgenden Zeiträume:
Diagnosefenster: 1. Januar 2013 gemäß den neuesten verfügbaren Daten.
Studientyp
Einschreibung (Tatsächlich)
Kontakte und Standorte
Studienorte
-
-
Leuven
-
Leuven, Leuven, Belgien, 3000
- Universitaire Ziekenhuizen Leuven (UZ Leuven)
-
-
-
-
Andalusia
-
Córdoba, Andalusia, Spanien, 14004
- Hospital Universitario Reina Sofia
-
-
Cantabria
-
Santander, Cantabria, Spanien, 39008
- Hospital Universitario Marques de Valdecilla (HUMV)
-
-
-
-
Ohio
-
Cleveland, Ohio, Vereinigte Staaten, 44195
- Cleveland Clinic Transplantation Center
-
Columbus, Ohio, Vereinigte Staaten, 43210
- The Ohio State University
-
-
Texas
-
Dallas, Texas, Vereinigte Staaten, 75246
- Baylor Scott and White Health Center for Advanced Heart and Lung Disease
-
-
Teilnahmekriterien
Zulassungskriterien
Studienberechtigtes Alter
- Erwachsene
- Älterer Erwachsener
Akzeptiert gesunde Freiwillige
Probenahmeverfahren
Studienpopulation
Beschreibung
Einschlusskriterien:
- Erwachsene Patienten ≥ 18 Jahre zum Zeitpunkt der CLAD-BOS-Diagnose
- Patienten mit einer klinischen CLAD-BOS-Diagnose bereits ab dem 1. Januar 2013
- Patienten mit CLAD-BOS-Diagnose des Arztes, die mindestens 12 Monate nach der Lungentransplantation gestellt wurde
- Die Patienten erhielten für mindestens einen Monat mindestens eine grundlegende Erhaltungstherapie mit Immunsuppressiva, einschließlich Tacrolimus, einem zweiten Wirkstoff wie, aber nicht beschränkt auf, Mycophenolatmofetil oder Azathioprin (oder einem anderen antiproliferativen Wirkstoff) und einem systemischen Kortikosteroid wie Prednison als drittem Wirkstoff vor dem Indexdatum. Solange das grundlegende Erhaltungsregime für den oben genannten Zeitraum beibehalten wird, gelten Patienten weiterhin als für die Studie geeignet, auch wenn sie zusätzlich zum grundlegenden Erhaltungsregime andere Immunsuppressiva erhalten.
Ausschlusskriterien:
- Patienten mit schweren Begleiterkrankungen zum Zeitpunkt des Indexdatums, die nach Einschätzung des Arztes das Fortschreiten und die Mortalität von CLAD-BOS beeinträchtigen können (z. B. maligne Erkrankungen, schwere chronische Erkrankungen)
- Patienten, die in den 4 Wochen vor dem Indexdatum oder in der Zeit nach der Diagnose Prüfpräparaten ausgesetzt waren
- Patienten mit bestätigtem anderen CLAD-Phänotyp (z. B. restriktivem Allograft-Syndrom) nach Einschätzung des Arztes.
Studienplan
Wie ist die Studie aufgebaut?
Designdetails
Kohorten und Interventionen
Gruppe / Kohorte |
|---|
|
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.
|
Was misst die Studie?
Primäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
|---|---|---|
|
Change Per Year in FEV1 Trajectory Starting From the Onset Date Through the End of the Post-diagnosis Period.
Zeitfenster: 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.
|
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.
Zeitfenster: 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.
|
From CLAD-BOS onset up to 3 years post-onset
|
Sekundäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
|---|---|---|
|
Age at Transplant
Zeitfenster: At transplant date
|
This secondary outcome summarizes descriptive characteristics collected at the time of lung transplantation.
|
At transplant date
|
|
Sex at Transplant
Zeitfenster: At transplant date
|
This secondary outcome summarizes descriptive characteristics collected at the time of lung transplantation.
|
At transplant date
|
|
Race
Zeitfenster: At transplant date
|
This secondary outcome summarizes descriptive characteristics collected at the time of lung transplantation.
|
At transplant date
|
|
Number of Participants With Pre-transplant Medical History and Lung Transplant History
Zeitfenster: Up to transplant date
|
This secondary outcome summarizes descriptive characteristics collected at the time of lung transplantation.
|
Up to transplant date
|
|
Time From Lung Transplantation to CLAD-BOS Onset
Zeitfenster: From transplant date to onset date
|
This secondary outcome summarizes descriptive characteristics collected at the time of lung transplantation.
|
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)
Zeitfenster: 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
|
Descriptive clinical characteristics collected following lung transplantation in patients diagnosed with CLAD-BOS.
Variables included the occurrence of acute rejection events, presence of lung opacities as documented by computed tomography (CT) scans, and signs, symptoms, or other clinical records related to mobility, self-care, usual activities, pain or discomfort, anxiety, and depression.
These data were collected for descriptive purposes only.
|
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
Zeitfenster: 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
|
Descriptive clinical characteristics collected following lung transplantation in patients diagnosed with CLAD-BOS.
Presence of donor-specific antibodies.
These data were collected for descriptive purposes only.
|
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)
Zeitfenster: 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
|
Descriptive clinical characteristics collected following lung transplantation in patients diagnosed with CLAD-BOS. These data were collected for descriptive purposes only. All available plethysmography assessments after lung transplantation were considered; therefore, data from multiple time points were collected and presented as mean and standard deviation. |
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
Zeitfenster: From CLAD-BOS onset up to 3 years post-onset
|
Change in Forced vital capacity (FVC) were evaluated from CLAD-BOS onset 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 at least 3 months later.
The FVC 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 to account for within-subject correlation over time.
Results are reported as model-based estimated mean changes from baseline in FVC 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 FVC Trajectory Over Time
Zeitfenster: From CLAD-BOS onset up to 3 years post-onset
|
Change in Forced vital capacity (FVC) were evaluated from CLAD-BOS onset 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 at least 3 months later.
The FVC 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 to account for within-subject correlation over time.
Model-based estimates of mean change from baseline in FVC (absolute values) are reported at prespecified time points after onset (1, 2, and 3 years).
The reported mean values represent estimates derived from the statistical model and are accompanied by standard errors.
|
From CLAD-BOS onset up to 3 years post-onset
|
|
Change Per Year in FEV1/FVC Trajectory
Zeitfenster: From CLAD-BOS onset up to 3 years post-onset
|
Forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) were measured by spirometry, and the FEV1/FVC ratio was derived accordingly. CLAD-BOS onset was defined as the first occurrence of an FEV1 value ≤80% of the patient's post-transplant best FEV1, confirmed by a subsequent measurement at least 3 months later, as documented in the medical records. The FEV1/FVC 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 to account for within-subject correlation over time. Results are reported as model-based estimated mean changes from baseline in FEV1/FVC 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/FVC Trajectory Over Time
Zeitfenster: From CLAD-BOS onset up to 3 years post-onset
|
Forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) were measured by spirometry, and the FEV1/FVC ratio was derived accordingly. CLAD-BOS onset was defined as the first occurrence of an FEV1 value ≤80% of the patient's post-transplant best FEV1, confirmed by a subsequent measurement at least 3 months later, as documented in the medical records. The FEV1/FVC 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 to account for within-subject correlation over time. Results are reported as model-based estimated mean changes from baseline in FEV1/FVC at prespecified time points after onset (1, 2, and 3 years). The reported mean values represent estimates derived from the statistical model, rather than arithmetic means of observed measurements. |
From CLAD-BOS onset up to 3 years post-onset
|
|
Change in FEF25-75% Trajectory Over Time
Zeitfenster: From CLAD-BOS onset up to 3 years post-onset
|
Change from baseline in Forced mid-expiratory flow (FEF25-75%), expressed as liters per second (L/s), was evaluated to characterize changes in mid-expiratory airflow following CLAD-BOS onset. CLAD-BOS onset was defined as the first occurrence of an FEV1 value ≤80% of the patient's post-transplant best FEV1, confirmed by a subsequent measurement. Repeated post-onset spirometry measurements collected during routine clinical practice were analyzed using a linear mixed-effects model with random subject-specific effects to account for within-subject correlation over time. Due to non-normal distribution, FEF25-75% values were log-transformed for model fitting. Model-based estimates of mean change from baseline on the original scale are reported at prespecified follow-up time points (at 1, 2 and 3 years). The reported values represent estimates derived from the statistical model rather than arithmetic means of observed measurements. |
From CLAD-BOS onset up to 3 years post-onset
|
|
Overall Survival (OS) From CLAD-BOS Onset
Zeitfenster: From CLAD-BOS onset through death, up to 120 months
|
Overall survival (OS) was defined as the time from CLAD-BOS onset to death from any cause.
OS was calculated as the time from the CLAD-BOS onset date to the earliest of the date of death or the last date the patient was known to be alive, expressed in months using a conversion factor of 30.4375 days per month.
Patients who were alive or had unknown vital status at the time of data abstraction were censored at the last date they were known to be alive.
Median OS and corresponding 95% confidence intervals were estimated using the Kaplan-Meier method, with confidence intervals calculated using the log-log transformation.
|
From CLAD-BOS onset through death, up to 120 months
|
|
Time to First CLAD-BOS Progression
Zeitfenster: From CLAD-BOS onset through death (median follow up time 38.6 months)
|
Time to first CLAD-BOS progression was defined as the time from CLAD-BOS onset to the first documented disease progression. Progression was defined as the earliest occurrence of any of the following events:
Median time to progression and 95% confidence intervals were estimated using the Kaplan-Meier method. |
From CLAD-BOS onset through death (median follow up time 38.6 months)
|
|
Cumulative Number of CLAD-BOS Progression Events Per Patient
Zeitfenster: From CLAD-BOS onset to last data available or death a median of 38.6 (max 173) months
|
Cumulative CLAD-BOS progression events were assessed from CLAD-BOS onset through the end of the post-diagnosis follow-up period.
CLAD-BOS progression was defined as the earliest occurrence of an absolute decrease in FEV1 of ≥10% or ≥200 mL combined with an absolute decrease in FEV1/FVC of >5% confirmed by a subsequent assessment, change in CLAD grade severity, re-transplantation, death from respiratory failure, or clinical judgment reporting CLAD-BOS progression in patient records.
Event counts and rates were analyzed using a negative binomial regression model with an offset for follow-up time.
|
From CLAD-BOS onset to last data available or death a median of 38.6 (max 173) months
|
|
Hospitalization Rate Due to Respiratory Failure
Zeitfenster: From CLAD-BOS onset to last data available or death a median of 38.6 (max 173) months
|
The rate of hospitalizations due to respiratory failure was assessed from the CLAD-BOS onset date through the end of the post-diagnosis period.
Hospitalization events attributed to respiratory failure were identified from patient medical records.
Event rates were estimated using a negative binomial regression model with an offset for patient observation time to account for variable observation duration.
Results are reported as rates per year with 95% confidence intervals.
|
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
Zeitfenster: From CLAD-BOS onset to last data available or death a median of 38.6 (max 173) months
|
The number of participants with concomitant respiratory diseases was assessed in the Full Analysis Set. Concomitant respiratory diseases were identified from patient records and coded using MedDRA (version 27.0) terminology. Results are summarized as the number and percentage of patients with at least one concomitant respiratory disease. Only concomitant respiratory disease categories reported in ≥ 5% of patients are presented. |
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
Zeitfenster: 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
|
The use of concomitant treatments and procedures for CLAD-BOS following lung transplantation was assessed in the Full Analysis Set based on medical record review. Concomitant treatments and procedures were defined as those administered or performed after CLAD-BOS onset. Results are reported as the number and percentage of patients receiving at least one concomitant treatment or procedure. Concomitant treatments were coded using WHO Drug Dictionary terminology (version March 2024), and procedures were summarized descriptively. Only treatments and procedures reported in ≥ 5% of patients are presented. |
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
Zeitfenster: From CLAD-BOS onset to last data available or death a median of 38.6 (max 173) months
|
The number of participants with concomitant non-respiratory diseases was assessed in the Full Analysis Set based on medical record review.
Concomitant non-respiratory diseases were coded using MedDRA (version 27.0) preferred terms and summarized descriptively.
Results are reported as the number and percentage of patients with at least one concomitant non-respiratory disease.
Only non-respiratory disease categories reported in ≥ 5% of patients are presented.
|
From CLAD-BOS onset to last data available or death a median of 38.6 (max 173) months
|
Mitarbeiter und Ermittler
Sponsor
Ermittler
- Studienleiter: Paola Castellani, MD, Zambon SpA
Studienaufzeichnungsdaten
Haupttermine studieren
Studienbeginn (Tatsächlich)
Primärer Abschluss (Tatsächlich)
Studienabschluss (Tatsächlich)
Studienanmeldedaten
Zuerst eingereicht
Zuerst eingereicht, das die QC-Kriterien erfüllt hat
Zuerst gepostet (Tatsächlich)
Studienaufzeichnungsaktualisierungen
Letztes Update gepostet (Tatsächlich)
Letztes eingereichtes Update, das die QC-Kriterien erfüllt
Zuletzt verifiziert
Mehr Informationen
Begriffe im Zusammenhang mit dieser Studie
Schlüsselwörter
Zusätzliche relevante MeSH-Bedingungen
Andere Studien-ID-Nummern
- Z8000N01
Plan für individuelle Teilnehmerdaten (IPD)
Planen Sie, individuelle Teilnehmerdaten (IPD) zu teilen?
Arzneimittel- und Geräteinformationen, Studienunterlagen
Studiert ein von der US-amerikanischen FDA reguliertes Arzneimittelprodukt
Studiert ein von der US-amerikanischen FDA reguliertes Geräteprodukt
Produkt, das in den USA hergestellt und aus den USA exportiert wird
Diese Informationen wurden ohne Änderungen direkt von der Website clinicaltrials.gov abgerufen. Wenn Sie Ihre Studiendaten ändern, entfernen oder aktualisieren möchten, wenden Sie sich bitte an register@clinicaltrials.gov. Sobald eine Änderung auf clinicaltrials.gov implementiert wird, wird diese automatisch auch auf unserer Website aktualisiert .