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
Tutkimuksen yleiskatsaus
Tila
Ehdot
Interventio / Hoito
Yksityiskohtainen kuvaus
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).
Opintotyyppi
Ilmoittautuminen (Todellinen)
Yhteystiedot ja paikat
Opiskelupaikat
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Guangdong
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Guangzhou, Guangdong, Kiina, 510120
- The First Affiliated Hospital of Guangzhou Medical University
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Osallistumiskriteerit
Kelpoisuusvaatimukset
Opintokelpoiset iät
- Lapsi
- Aikuinen
- Vanhempi Aikuinen
Hyväksyy terveitä vapaaehtoisia
Näytteenottomenetelmä
Tutkimusväestö
Kuvaus
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
Opintosuunnitelma
Miten tutkimus on suunniteltu?
Suunnittelun yksityiskohdat
Kohortit ja interventiot
Ryhmä/Kohortti |
Interventio / Hoito |
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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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Mitä tutkimuksessa mitataan?
Ensisijaiset tulostoimenpiteet
Tulosmittaus |
Toimenpiteen kuvaus |
Aikaikkuna |
|---|---|---|
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Plasma isavuconazole trough concentration
Aikaikkuna: 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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Toissijaiset tulostoimenpiteet
Tulosmittaus |
Toimenpiteen kuvaus |
Aikaikkuna |
|---|---|---|
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Determinants of isavuconazole trough concentration
Aikaikkuna: 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)
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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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Yhteistyökumppanit ja tutkijat
Sponsori
Opintojen ennätyspäivät
Opi tärkeimmät päivämäärät
Opiskelun aloitus (Todellinen)
Ensisijainen valmistuminen (Todellinen)
Opintojen valmistuminen (Todellinen)
Opintoihin ilmoittautumispäivät
Ensimmäinen lähetetty
Ensimmäinen toimitettu, joka täytti QC-kriteerit
Ensimmäinen Lähetetty (Todellinen)
Tutkimustietojen päivitykset
Viimeisin päivitys julkaistu (Todellinen)
Viimeisin lähetetty päivitys, joka täytti QC-kriteerit
Viimeksi vahvistettu
Lisää tietoa
Tähän tutkimukseen liittyvät termit
Avainsanat
Muita asiaankuuluvia MeSH-ehtoja
Muut tutkimustunnusnumerot
- ES-2025-K203-01
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