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
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 110
- 试验地点
- 1
- 主要终点
- Plasma isavuconazole trough concentration
研究概览
简要总结
Isavuconazole is an antifungal medicine used to prevent or treat serious fungal infections in people who have received a solid organ transplant (mainly lung, and also kidney or liver) or a hematopoietic stem cell (bone marrow) transplant. Because these patients take medicines that suppress the immune system, they are at high risk of fungal infections. The amount of isavuconazole in the blood can vary widely from person to person, and it is not fully understood what drives these differences or whether higher blood levels are linked to side effects such as liver problems.This study reviews the medical records of transplant recipients who were treated with isavuconazole at a single hospital in China between January 2024 and April 2026. Using results from routine therapeutic drug monitoring (blood tests that measure the drug level), the researchers describe how isavuconazole blood levels are distributed, how much they vary within and between patients, and which clinical and genetic factors are associated with higher or lower levels. The study also examines whether isavuconazole blood levels are related to liver function abnormalities and to survival. Because this is an observational study, no treatment was assigned for research purposes; the study only analyzes data collected during routine clinical care. The findings are intended to help guide individualized dosing and monitoring of isavuconazole in transplant recipients.
详细描述
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).
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Retrospective
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •No available plasma isavuconazole trough concentration
- •Incomplete key clinical or dosing records precluding analysis
结局指标
主要结局
Plasma isavuconazole trough concentration
时间窗: 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.
次要结局
- Determinants of isavuconazole trough concentration(During the study period (January 2024 to April 2026))
- Attainment of the target trough window (1-7 µg/mL)(During the study period (January 2024 to April 2026))
- Association between isavuconazole exposure and hepatic function abnormality(During the study period (January 2024 to April 2026))
- Correlation between isavuconazole and calcineurin-inhibitor concentrations(During the study period (January 2024 to April 2026))
- All-cause mortality(During the study period (January 2024 to April 2026))
研究者
Zhibin Xu
PhD Candidate
Guangzhou Institute of Respiratory Disease