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Een retrospectief overzichtsonderzoek bij patiënten met chronische longtransplantaatdysfunctie - Bronchiolitis Obliterans Syndroom (CLAD-BOS) na longtransplantatie

26 augustus 2026 bijgewerkt door: Zambon SpA
Het doel van deze studie is om het geforceerde expiratoire volume in 1 seconde (FEV1) afname en de natuurlijke ziekte-evolutie te beschrijven bij patiënten getroffen door CLAD-BOS na longtransplantatie en die als standaardbehandeling een immunosuppressieve therapie krijgen.

Studie Overzicht

Toestand

Voltooid

Conditie

Gedetailleerde beschrijving

Dit is een retrospectief, multinationaal, multicenter overzichtsonderzoek van volwassen patiënten met de klinisch gediagnosticeerde CLAD-BOS na longtransplantatie. Alle gegevens zullen retrospectief worden verzameld uit patiëntendossiers, beginnend vanaf de longtransplantatiedatum tot en met de laatste datum van beschikbare gegevens, en als zodanig zullen er geen interventies worden toegepast als onderdeel van dit onderzoek.

De observatieperiode voor elke patiënt loopt van de datum van de longtransplantatie tot de laatste datum waarop de beschikbare gegevens beschikbaar zijn of het overlijden, afhankelijk van wat zich eerder voordoet, en omvat de volgende tijdsperioden:

Diagnoseperiode: 1 januari 2013 op basis van de meest recente beschikbare gegevens.

Studietype

Observationeel

Inschrijving (Werkelijk)

284

Contacten en locaties

In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.

Studie Locaties

  • België
    • Leuven
      • Leuven, Leuven, België, 3000
        • Universitaire Ziekenhuizen Leuven (UZ Leuven)
  • Spanje
    • Andalusia
      • Córdoba, Andalusia, Spanje, 14004
        • Hospital Universitario Reina Sofia
    • Cantabria
      • Santander, Cantabria, Spanje, 39008
        • Hospital Universitario Marques de Valdecilla (HUMV)
  • Verenigde Staten
    • Ohio
      • Cleveland, Ohio, Verenigde Staten, 44195
        • Cleveland Clinic Transplantation Center
      • Columbus, Ohio, Verenigde Staten, 43210
        • The Ohio State University
    • Texas
      • Dallas, Texas, Verenigde Staten, 75246
        • Baylor Scott and White Health Center for Advanced Heart and Lung Disease

Deelname Criteria

Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.

Geschiktheidscriteria

Leeftijden die in aanmerking komen voor studie

  • Volwassen
  • Oudere volwassene

Accepteert gezonde vrijwilligers

Nee

Bemonsteringsmethode

Kanssteekproef

Studie Bevolking

De onderzoekspopulatie omvat volwassen patiënten van ≥ 18 jaar die een longtransplantatie hebben ondergaan en bij wie vanaf 1 januari 2013 de diagnose CLAD-BOS wordt gesteld na de transplantatie.

Beschrijving

Inclusiecriteria:

  1. Volwassen patiënten ≥ 18 jaar oud op de datum van CLAD-BOS-diagnose
  2. Patiënten met een CLAD-BOS-artsdiagnose vanaf 1 januari 2013
  3. Patiënten met een klinische CLAD-BOS-diagnose gesteld ten minste 12 maanden na de longtransplantatie
  4. Patiënten kregen gedurende ten minste 1 maand ten minste een basisonderhoudsregime van immunosuppressiva, waaronder tacrolimus, een tweede middel zoals maar niet beperkt tot mycofenolaatmofetil of azathioprine (of een ander antiproliferatief middel) en een systemisch corticosteroïde zoals prednison als derde middel. vóór de indexdatum. Zolang het basisonderhoudsregime gedurende de bovengenoemde periode wordt gehandhaafd, zullen patiënten nog steeds in aanmerking komen voor het onderzoek, zelfs als zij naast het basisonderhoudsregime andere immunosuppressiva krijgen.

Uitsluitingscriteria:

  1. Patiënten met een ernstige bijkomende ziekte op het moment van de indexdatum, die volgens het oordeel van de arts de progressie en mortaliteit van CLAD-BOS kan verstoren (bijv. maligniteiten, ernstige chronische ziekten)
  2. Patiënten die zijn blootgesteld aan medische onderzoeksproducten in de vier weken voorafgaand aan de indexdatum of tijdens de periode na de diagnose
  3. Patiënten met een bevestigd ander CLAD-fenotype (bijv. restrictief allograftsyndroom) volgens het oordeel van de arts.

Studie plan

Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.

Hoe is de studie opgezet?

Ontwerpdetails

Cohorten en interventies

Groep / Cohort
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.

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Change Per Year in FEV1 Trajectory Starting From the Onset Date Through the End of the Post-diagnosis Period.
Tijdsspanne: 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.
Tijdsspanne: 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

Secundaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Age at Transplant
Tijdsspanne: At transplant date
This secondary outcome summarizes descriptive characteristics collected at the time of lung transplantation.
At transplant date
Sex at Transplant
Tijdsspanne: At transplant date
This secondary outcome summarizes descriptive characteristics collected at the time of lung transplantation.
At transplant date
Race
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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)
Tijdsspanne: 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
Tijdsspanne: 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)
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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:

  • an absolute decrease in FEV1 of ≥10% or ≥200 mL from a previously available spirometry assessment with a concomitant absolute decrease in FEV1/FVC of >5% confirmed at least 2 weeks apart;
  • change in CLAD grade severity;
  • re-transplantation;
  • death from respiratory failure;
  • or clinical judgment reporting CLAD-BOS progression in medical records. Patients without documented CLAD-BOS progression at the time of data abstraction were censored at the date of the last available assessment.

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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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

Medewerkers en onderzoekers

Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.

Sponsor

Zambon SpA

Onderzoekers

  • Studie directeur: Paola Castellani, MD, Zambon SpA

Studie record data

Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.

Bestudeer belangrijke data

Studie start (Werkelijk)

27 juni 2024

Primaire voltooiing (Werkelijk)

9 april 2025

Studie voltooiing (Werkelijk)

9 april 2025

Studieregistratiedata

Eerst ingediend

8 juli 2024

Eerst ingediend dat voldeed aan de QC-criteria

15 juli 2024

Eerst geplaatst (Werkelijk)

16 juli 2024

Updates van studierecords

Laatste update geplaatst (Werkelijk)

1 september 2026

Laatste update ingediend die voldeed aan QC-criteria

26 augustus 2026

Laatst geverifieerd

1 augustus 2026

Meer informatie

Termen gerelateerd aan deze studie

Trefwoorden

Aanvullende relevante MeSH-voorwaarden

Andere studie-ID-nummers

  • Z8000N01

Plan Individuele Deelnemersgegevens (IPD)

Bent u van plan om gegevens van individuele deelnemers (IPD) te delen?

NEE

Informatie over medicijnen en apparaten, studiedocumenten

Bestudeert een door de Amerikaanse FDA gereguleerd geneesmiddel

Nee

Bestudeert een door de Amerikaanse FDA gereguleerd apparaatproduct

Nee

product vervaardigd in en geëxporteerd uit de V.S.

Nee

Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .

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