Isavuconazole Therapeutic Drug Monitoring in Transplant Recipients (TRIM-1)
Therapeutic Drug Monitoring of Isavuconazole in Solid Organ and Hematopoietic Stem Cell Transplant Recipients: A Single-Center Retrospective Cohort Study of Plasma Trough Exposure, Its Determinants, and Hepatic Safety
Descripción general del estudio
Estado
Condiciones
Intervención / Tratamiento
Descripción detallada
This is a single-center, retrospective, observational cohort study conducted at the First Affiliated Hospital of Guangzhou Medical University. It includes solid organ transplant (lung, kidney, liver) and hematopoietic stem cell transplant recipients who received isavuconazole for the prophylaxis or treatment of invasive fungal infections between January 2024 and April 2026 and who had at least one plasma isavuconazole trough concentration measured by routine therapeutic drug monitoring (TDM).
The primary objective is to characterize the distribution and the within- and between-patient variability of isavuconazole plasma trough concentrations and to identify clinical and pharmacogenetic determinants of drug exposure. Secondary objectives include describing attainment of a pre-specified target trough window (1-7 µg/mL); the relationship between isavuconazole exposure and calcineurin-inhibitor (tacrolimus, cyclosporine) concentrations; and the association of isavuconazole exposure with hepatic function abnormalities and all-cause mortality.
Demographic, clinical, laboratory, immunosuppressant, CYP3A5 genotype, and TDM data are extracted from medical records. Trough concentrations are analyzed at both the measurement level and the patient level. Determinants of log-transformed trough concentration are evaluated using linear mixed-effects models with a patient-level random intercept to account for repeated measurements. Subgroup analyses are pre-specified by transplant type (lung, kidney, liver, hematopoietic stem cell), treatment scenario (prophylaxis vs treatment), age (adult vs pediatric), and CYP3A5 genotype, with case-series description for small subgroups; a sensitivity analysis restricted to adults is also performed. No study intervention is assigned; all data reflect routine clinical care. The study is reported in accordance with the STROBE statement and was approved by the institutional ethics committee (approval number ES-2025-K203-01).
Tipo de estudio
Inscripción (Actual)
Contactos y Ubicaciones
Ubicaciones de estudio
-
-
Guangdong
-
Guangzhou, Guangdong, Porcelana, 510120
- The First Affiliated Hospital of Guangzhou Medical University
-
-
Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
- Niño
- Adulto
- Adulto Mayor
Acepta Voluntarios Saludables
Método de muestreo
Población de estudio
Descripción
Inclusion Criteria:
- Recipients of solid organ transplantation (lung, kidney, or liver) or hematopoietic stem cell transplantation
- Received isavuconazole for prophylaxis or treatment of invasive fungal infection during the study period, with traceable prescription and administration records
- Isavuconazole treatment duration of at least 7 days and at least one measured plasma isavuconazole trough concentration
- Adequate follow-up information to assess the main study variables
Exclusion Criteria:
- No available plasma isavuconazole trough concentration
- Incomplete key clinical or dosing records precluding analysis
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
Cohortes e Intervenciones
Grupo / Cohorte |
Intervención / Tratamiento |
|---|---|
|
Treatment cohort
Transplant recipients who received isavuconazole for the treatment of suspected or documented invasive fungal infection.
|
Isavuconazole administered orally or intravenously as part of routine clinical care; plasma trough concentrations measured by routine therapeutic drug monitoring.
|
|
Prophylaxis cohort
Transplant recipients who received isavuconazole for the prophylaxis of invasive fungal infection.
|
Isavuconazole administered orally or intravenously as part of routine clinical care; plasma trough concentrations measured by routine therapeutic drug monitoring.
|
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Plasma isavuconazole trough concentration
Periodo de tiempo: During the study period (January 2024 to April 2026)
|
Distribution (median [IQR], range) and within- and between-patient variability (coefficient of variation) of plasma isavuconazole trough concentrations obtained by routine therapeutic drug monitoring.
|
During the study period (January 2024 to April 2026)
|
Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Determinants of isavuconazole trough concentration
Periodo de tiempo: During the study period (January 2024 to April 2026)
|
Clinical and pharmacogenetic factors independently associated with log-transformed trough concentration, estimated by linear mixed-effects models (e.g., weight-adjusted daily dose, serum albumin, total bilirubin, estimated glomerular filtration rate, hemoglobin, transplant type, CYP3A5 genotype).
|
During the study period (January 2024 to April 2026)
|
|
Attainment of the target trough window (1-7 µg/mL)
Periodo de tiempo: During the study period (January 2024 to April 2026)
|
Proportion of trough measurements falling within the pre-specified target window of 1-7 µg/mL, and below (<1 µg/mL) or above (>7 µg/mL) it.
|
During the study period (January 2024 to April 2026)
|
|
Association between isavuconazole exposure and hepatic function abnormality
Periodo de tiempo: During the study period (January 2024 to April 2026)
|
Association between isavuconazole trough concentration and hepatic function abnormality, defined as alanine or aspartate aminotransferase >120 U/L and/or total bilirubin >21 µmol/L.
|
During the study period (January 2024 to April 2026)
|
|
Correlation between isavuconazole and calcineurin-inhibitor concentrations
Periodo de tiempo: During the study period (January 2024 to April 2026)
|
Spearman correlation between concurrently measured isavuconazole trough concentrations and tacrolimus or cyclosporine blood concentrations.
|
During the study period (January 2024 to April 2026)
|
|
All-cause mortality
Periodo de tiempo: During the study period (January 2024 to April 2026)
|
All-cause mortality during follow-up and its association with isavuconazole exposure.
|
During the study period (January 2024 to April 2026)
|
Colaboradores e Investigadores
Patrocinador
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Actual)
Finalización primaria (Actual)
Finalización del estudio (Actual)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
- ES-2025-K203-01
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .