Accepted for/Published in: JMIR Research Protocols
Date Submitted: Feb 12, 2025
Date Accepted: May 29, 2025
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Optimization of preemptive therapy for cytomegalovirus with valganciclovir based on therapeutic drug monitoring: Protocol for a phase II, single-center, single-arm trial
ABSTRACT
Background:
Valganciclovir (VGCV) is the first-line drug for preemptive therapy of cytomegalovirus (CMV). However, even when administered at the dose specified in the package insert, there is significant inter-individual variability in the plasma concentrations of ganciclovir. In addition, correlations between the area under the concentration–time curve (AUC) and therapeutic efficacy or adverse events have been reported. Therefore, therapeutic drug monitoring (TDM) can be used to improve the efficacy and safety of preemptive VGCV therapy.
Objective:
This study aims to evaluate whether the dosage adjustment of VGCV based on TDM in patients undergoing preemptive therapy for CMV is associated with a successful completion rate of treatment without severe hematological adverse effects.
Methods:
This ongoing phase II, single-center, single-arm trial aims to enroll 40 patients admitted at the Department of Rheumatology and Clinical Immunology, Kobe University Hospital who will receive oral VGCV as preemptive therapy for CMV. Participants will begin treatment with VGCV at the dose recommended in the package insert, with subsequent dose adjustments based on weekly TDM results. The primary endpoint will be the proportion of patients who achieve CMV antigenemia negativity within 3 weeks without serious adverse events. The secondary endpoints will include weekly changes in CMV antigen levels, total VGCV dose, and duration of preemptive therapy. For safety evaluation, the occurrence, type, and severity of VGCV-related adverse events will be analyzed. Additionally, the study will explore the correlations between the efficacy and safety of preemptive therapy and the pharmacokinetic parameters of GCV, CMV-polymerase chain reaction values, and NUDT15 genetic polymorphisms. The correlation between GCV plasma concentrations and blood concentrations using dried blood spots will be examined.
Results:
This study began with patient recruitment in September 2024, with two participants enrolled as of February 1, 2025. The target enrollment is 40 participants, and the anticipated study completion is set for July 2027.
Conclusions:
This is the first study to investigate the impact of TDM intervention in patients receiving VGCV as preemptive therapy. The findings are postulated to provide valuable evidence regarding the utility of TDM in patients receiving VGCV as preemptive therapy. Clinical Trial: Japan Registry of Clinical Trials jRCTs051240080; https://jrct.niph.go.jp/latest-detail/jRCTs051240080
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