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

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.

Study Overview

• Status: Completed
• Conditions: Invasive Fungal Infections; Kidney Transplantation; Lung Transplantation; Hematopoietic Stem Cell Transplantation (HSCT); Liver Transplantation (LT)
• Intervention / Treatment: Drug: Isavuconazole

Detailed Description

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).

• Study Type: Observational
• Enrollment (Actual): 110

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510120
      • The First Affiliated Hospital of Guangzhou Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Consecutive solid organ (lung, kidney, liver) and hematopoietic stem cell transplant recipients who received isavuconazole and underwent routine therapeutic drug monitoring at a single tertiary-care hospital in China between January 2024 and April 2026. A total of 110 recipients were included (89 lung, 6 kidney, 2 liver, and 13 hematopoietic stem cell transplant), contributing 427 trough concentration measurements.

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Treatment cohort; Transplant recipients who received isavuconazole for the treatment of suspected or documented invasive fungal infection.	Drug: Isavuconazole; 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.	Drug: Isavuconazole; Isavuconazole administered orally or intravenously as part of routine clinical care; plasma trough concentrations measured by routine therapeutic drug monitoring.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma isavuconazole trough concentration	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)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Determinants of isavuconazole trough concentration	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)	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	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	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	All-cause mortality during follow-up and its association with isavuconazole exposure.	During the study period (January 2024 to April 2026)

Collaborators and Investigators

• Sponsor: Zhibin Xu

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2024
• Primary Completion (Actual): April 1, 2026
• Study Completion (Actual): April 1, 2026

Study Registration Dates

• First Submitted: July 16, 2026
• First Submitted That Met QC Criteria: July 16, 2026
• First Posted (Actual): July 21, 2026

Study Record Updates

• Last Update Posted (Actual): July 21, 2026
• Last Update Submitted That Met QC Criteria: July 16, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Isavuconazole; Therapeutic Drug Monitoring; CYP3A5; Trough Concentration; Antifungal Triazole; Drug Exposure Variability
• Additional Relevant MeSH Terms: Infections; Bacterial Infections and Mycoses; Mycoses; Invasive Fungal Infections; isavuconazole
• Other Study ID Numbers: ES-2025-K203-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No