Blood Exosomal Multi-omics and Lung Radiomics for Predicting Efficacy and Prognosis of Severe Eosinophilic ACOS With Biologics (ACOS)
21 de mayo de 2026 actualizado por: Yang Jin, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Blood Exosomal Multi-omics and Lung Radiomics for Predicting Efficacy and Prognosis of Severe Eosinophilic ACOS (Asthma-COPD Overlap Syndrome) Treated With Different Biologics: A Real-World Observational Study
Firstly, to screen blood exosomal multi-omics (transcriptomics, proteomics, metabolomics) and lung radiomics (HRCT, Xe129MRI) biomarkers that can predict efficacy and prognosis in severe eosinophilic ACOS (asthma-COPD overlap) patients treated with different biologics (benralizumab, mepolizumab, dupilumab).
Then, to prospectively follow patients for 48 weeks after biologic initiation and collect clinical data, blood samples, and imaging features.
Finally, to build a multi-dimensional predictive model for efficacy and prognosis of severe eosinophilic ACOS.
Descripción general del estudio
Estado
Aún no reclutando
Condiciones
Descripción detallada
Firstly, eligible patients (age ≥14 years, diagnosis of severe eosinophilic ACOS, blood eosinophils ≥150/μL within 3 months or ≥300/μL within 1 year, and clinician decision to start a biologic) will be enrolled. Exclusion criteria include concurrent trial participation, allergy to biologics, malignancy, or prior biologic use.
Then, patients are followed for 48 weeks after the first biologic dose. Visits occur at weeks 0, 1, 2, 4, 8, 16, 24, 40, and 48. Data collected include demographics, medical history, ACQ-6, MiniAQLQ, pre-BD FEV1, exacerbations, medication use, adverse events, and blood routine tests (residual samples for exosome analysis). HRCT and Xe129MRI are optional.
Next, the primary outcome is the composite endpoint of efficacy and prognosis at week 48, defined as: no ACOS exacerbation, no oral corticosteroids, pre-BD FEV1 improvement ≥100 mL from baseline, and ACQ-6 score <1.5 (or ≤0.75). Secondary outcomes include changes in ACQ-6, FEV1, annualized exacerbation rate, MiniAQLQ, OCS dose reduction, and blood exosomal multi-omics and lung radiomics biomarkers.
Finally, statistical analyses include descriptive statistics, paired t-test/Wilcoxon, ANOVA/Kruskal-Wallis, mixed-effects model for repeated measures (MMRM), differential expression analysis (DESeq2/limma), pathway enrichment, machine learning (LASSO, random forest), ROC curves, logistic regression, and Cox regression. A total of 500 patients will be enrolled from multiple centers in China.
Tipo de estudio
De observación
Inscripción (Estimado)
500
Contactos y Ubicaciones
Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.
Estudio Contacto
- Nombre: Qi Huang
- Número de teléfono: +86 15827329098
- Correo electrónico: huangqi66@126.com
Ubicaciones de estudio
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Hubei
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Wuhan, Hubei, Porcelana, 430022
- Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
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Contacto:
- Qi Huang
- Número de teléfono: +86 15827329098
- Correo electrónico: huangqi66@126.com
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-
Criterios de participación
Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.
Criterio de elegibilidad
Edades elegibles para estudiar
- Niño
- Adulto
- Adulto Mayor
Acepta Voluntarios Saludables
No
Método de muestreo
Muestra no probabilística
Población de estudio
Patients aged 14 years or older with a confirmed diagnosis of severe eosinophilic ACOS (asthma-COPD overlap) who are prescribed a biologic (benralizumab, mepolizumab, or dupilumab) by their treating physician according to routine clinical practice.
The study population is recruited from outpatient and inpatient respiratory departments of multiple hospitals in China, including Union Hospital (Tongji Medical College, Huazhong University of Science and Technology) and its collaborating centers.
Descripción
Inclusion Criteria:
- Age ≥ 14 years
- Clinician decision to start biologic (benralizumab, mepolizumab, or dupilumab) for severe eosinophilic ACOS
- Blood eosinophils ≥150/μL within 3 months prior to informed consent, or ≥300/μL within 1 year prior
- Signed written informed consent
Exclusion Criteria:
- Currently participating in any other interventional clinical trial
- Known allergy or hypersensitivity to any component of the study drugs
- Any type of malignancy
- Prior or current biologic treatment for ACOS
Plan de estudios
Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.
¿Cómo está diseñado el estudio?
Detalles de diseño
Cohortes e Intervenciones
Grupo / Cohorte |
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Benralizumab Group
Patients with severe eosinophilic ACOS receiving benralizumab as prescribed by their treating physician according to routine clinical practice.
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Mepolizumab Group
Patients with severe eosinophilic ACOS receiving mepolizumab as prescribed by their treating physician according to routine clinical practice.
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Dupilumab Group
Patients with severe eosinophilic ACOS receiving dupilumab as prescribed by their treating physician according to routine clinical practice.
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Composite efficacy and prognosis endpoint at week 48 in severe eosinophilic ACOS
Periodo de tiempo: 48 weeks after the first dose of biologic
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We define the composite endpoint as achieving ALL of the following at week 48: (1) no ACOS exacerbation (worsening of respiratory symptoms requiring systemic corticosteroids ≥3 days, emergency visit <24h, or hospitalization ≥24h); (2) no use of oral corticosteroids (OCS); (3) pre-bronchodilator FEV1 improvement ≥100 mL from baseline; (4) ACQ-6 score <1.5 (or ≤0.75).
The proportion of patients meeting all four criteria will be calculated.
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48 weeks after the first dose of biologic
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Change in Asthma Control Questionnaire-6 (ACQ-6) score
Periodo de tiempo: Baseline to 48 weeks
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ACQ-6 is a validated questionnaire (6 items, score 0-6, lower = better control).
Change from baseline will be assessed at weeks 1,2,4,8,16,24,40,48.
Mean difference and standard deviation will be reported.
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Baseline to 48 weeks
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Change in pre-bronchodilator FEV1 (mL)
Periodo de tiempo: Baseline to 48 weeks
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FEV1 (forced expiratory volume in 1 second) will be measured using spirometry according to international standards (ATS/ERS).
Change in mL from baseline will be calculated at weeks 8, 16, and 48.
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Baseline to 48 weeks
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Annualized rate of ACOS exacerbations
Periodo de tiempo: 48 weeks
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Number of ACOS exacerbations per year during the 48-week follow-up.
Exacerbation defined as worsening of respiratory symptoms requiring systemic corticosteroids (≥3 days), emergency department visit (<24 hours), or hospitalization (≥24 hours).
Rate = (total exacerbations × 365.25) / follow-up days.
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48 weeks
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Change in Mini Asthma Quality of Life Questionnaire (MiniAQLQ) score
Periodo de tiempo: Baseline to 48 weeks
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MiniAQLQ is a 15-item questionnaire (score 1-7, higher = better quality of life).
Change from baseline will be assessed at weeks 8, 16, 24, and 48.
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Baseline to 48 weeks
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Change in blood exosomal multi-omics biomarkers
Periodo de tiempo: Baseline to 48 weeks
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Residual blood from routine tests (2-3 mL per time point at weeks 0,4,8,16,24,40,48) will be used to isolate exosomes.
Transcriptomics (RNA-seq), proteomics (mass spectrometry), and metabolomics (LC-MS) profiles will be compared between baseline and week 48.
Differentially expressed features (|log2FC|>1, FDR<0.05) will be reported.
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Baseline to 48 weeks
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Change in lung radiomics features
Periodo de tiempo: Baseline to 48 weeks
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For patients who undergo HRCT or Xe129MRI (optional), radiomics features (e.g., texture, shape, intensity) will be extracted using standard software.
Changes from baseline to week 24 and 48 will be analyzed.
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Baseline to 48 weeks
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Colaboradores e Investigadores
Aquí es donde encontrará personas y organizaciones involucradas en este estudio.
Fechas de registro del estudio
Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.
Fechas importantes del estudio
Inicio del estudio (Estimado)
1 de junio de 2026
Finalización primaria (Estimado)
1 de junio de 2028
Finalización del estudio (Estimado)
1 de julio de 2028
Fechas de registro del estudio
Enviado por primera vez
17 de mayo de 2026
Primero enviado que cumplió con los criterios de control de calidad
21 de mayo de 2026
Publicado por primera vez (Actual)
22 de mayo de 2026
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
22 de mayo de 2026
Última actualización enviada que cumplió con los criterios de control de calidad
21 de mayo de 2026
Última verificación
1 de mayo de 2026
Más información
Términos relacionados con este estudio
Palabras clave
Otros números de identificación del estudio
- XHJY202605
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
No
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
No
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