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
Обзор исследования
Статус
Условия
Вмешательство/лечение
Подробное описание
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).
Тип исследования
Регистрация (Действительный)
Контакты и местонахождение
Места учебы
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Guangdong
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Guangzhou, Guangdong, Китай, 510120
- The First Affiliated Hospital of Guangzhou Medical University
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Критерии участия
Критерии приемлемости
Возраст, подходящий для обучения
- Ребенок
- Взрослый
- Пожилой взрослый
Принимает здоровых добровольцев
Метод выборки
Исследуемая популяция
Описание
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
Учебный план
Как устроено исследование?
Детали дизайна
Когорты и вмешательства
Группа / когорта |
Вмешательство/лечение |
|---|---|
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Treatment cohort
Transplant recipients who received isavuconazole for the treatment of suspected or documented invasive fungal infection.
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Isavuconazole administered orally or intravenously as part of routine clinical care; plasma trough concentrations measured by routine therapeutic drug monitoring.
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Prophylaxis cohort
Transplant recipients who received isavuconazole for the prophylaxis of invasive fungal infection.
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Isavuconazole administered orally or intravenously as part of routine clinical care; plasma trough concentrations measured by routine therapeutic drug monitoring.
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Что измеряет исследование?
Первичные показатели результатов
Мера результата |
Мера Описание |
Временное ограничение |
|---|---|---|
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Plasma isavuconazole trough concentration
Временное ограничение: During the study period (January 2024 to April 2026)
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Distribution (median [IQR], range) and within- and between-patient variability (coefficient of variation) of plasma isavuconazole trough concentrations obtained by routine therapeutic drug monitoring.
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During the study period (January 2024 to April 2026)
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Вторичные показатели результатов
Мера результата |
Мера Описание |
Временное ограничение |
|---|---|---|
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Determinants of isavuconazole trough concentration
Временное ограничение: During the study period (January 2024 to April 2026)
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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).
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During the study period (January 2024 to April 2026)
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Attainment of the target trough window (1-7 µg/mL)
Временное ограничение: During the study period (January 2024 to April 2026)
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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.
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During the study period (January 2024 to April 2026)
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Association between isavuconazole exposure and hepatic function abnormality
Временное ограничение: During the study period (January 2024 to April 2026)
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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.
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During the study period (January 2024 to April 2026)
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Correlation between isavuconazole and calcineurin-inhibitor concentrations
Временное ограничение: During the study period (January 2024 to April 2026)
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Spearman correlation between concurrently measured isavuconazole trough concentrations and tacrolimus or cyclosporine blood concentrations.
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During the study period (January 2024 to April 2026)
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All-cause mortality
Временное ограничение: During the study period (January 2024 to April 2026)
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All-cause mortality during follow-up and its association with isavuconazole exposure.
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During the study period (January 2024 to April 2026)
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Соавторы и исследователи
Спонсор
Даты записи исследования
Изучение основных дат
Начало исследования (Действительный)
Первичное завершение (Действительный)
Завершение исследования (Действительный)
Даты регистрации исследования
Первый отправленный
Впервые представлено, что соответствует критериям контроля качества
Первый опубликованный (Действительный)
Обновления учебных записей
Последнее опубликованное обновление (Действительный)
Последнее отправленное обновление, отвечающее критериям контроля качества
Последняя проверка
Дополнительная информация
Термины, связанные с этим исследованием
Ключевые слова
Дополнительные соответствующие термины MeSH
Другие идентификационные номера исследования
- ES-2025-K203-01
Планирование данных отдельных участников (IPD)
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Информация о лекарствах и устройствах, исследовательские документы
Изучает лекарственный продукт, регулируемый FDA США.
Изучает продукт устройства, регулируемый Управлением по санитарному надзору за качеством пищевых продуктов и медикаментов США.
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