A Phase 4 interventional study of Chronotherapy-based individualized low-morning high-evening tacrolimus dosing and conventional dosing regimen in End-Stage Renal Disease, sponsored by The First Affiliated Hospital of Guangzhou Medical University. Not yet recruiting at 1 site in China. Open to participants aged 18 Years to 70 Years. Per ClinicalTrials.gov, last updated 2026-10-16.
Sponsored by The First Affiliated Hospital of Guangzhou Medical University · Phase 4, Interventional, and Treatment
The goal of this clinical trial is to evaluate whether chronopharmacokinetic model-guided individualized unequal twice-daily tacrolimus dosing improves renal allograft function and reduces acute rejection in stable kidney transplant recipients. The main questions it aims to answer are:
Does chrono-individualized tacrolimus dosing preserve graft renal function (eGFR) compared with conventional equal twice-daily dosing? Does chrono-individualized tacrolimus dosing lower the incidence of acute rejection in kidney transplant recipients? Researchers will compare recipients receiving chronopharmacokinetic-guided "low morning, high evening" individualized tacrolimus doses to recipients receiving conventional equal twice-daily tacrolimus doses to see if the chrono-individualized regimen improves renal function and reduces acute rejection risk.
Participants will:
Be randomly assigned to one of two tacrolimus dosing groups at a 1:1 ratio Receive routine immunosuppressive therapy and follow-up for 12 months Undergo blood sampling for tacrolimus concentration, calcineurin activity and multi-omics biomarker detection Complete regular clinical assessments of graft function, adverse events and rejection episodes
Tacrolimus (TAC) is the most commonly used calcineurin inhibitor after kidney transplantation; however, it has a narrow therapeutic window, high intrapatient variability, and exhibits marked diurnal (chronopharmacokinetic) differences in its pharmacokinetics. Our center performs approximately 100 kidney transplant surgeries per year and routinely uses a classic triple immunosuppressive regimen based on TAC combined with mycophenolate mofetil (MMF)/mycophenolate sodium (MPS) and glucocorticoids, providing a stable foundation for follow-up and research implementation in kidney transplant recipients. Both previously published literature and our center's earlier TAC pharmacokinetic (PK) data suggest that when the immediate-release (IR) formulation of TAC is administered as twice-daily equal doses, significant chronopharmacokinetic differences emerge: the morning dose produces higher exposure and peak concentration, whereas the evening dose yields relatively lower exposure-that is, a "high in the morning, low in the evening" biphasic concentration-time profile. Morning exposure is generally higher than evening exposure, and large peak-to-trough fluctuations may increase the risks of nephrotoxicity, metabolic abnormalities, and neurotoxicity.
This study will employ a multicenter, prospective, randomized controlled design and plans to enroll 100 stable-phase kidney transplant recipients, who will be randomized at a 1:1 ratio to either the chrono-individualized dosing group (receiving a "low in the morning, high in the evening" individualized dose regimen guided by the chronopharmacokinetic model) or the conventional equal-dose control group, with a total observation period of 12 months. The primary study endpoints include changes in graft renal function (eGFR) and the incidence of biopsy-proven or clinically diagnosed acute rejection. Secondary study endpoints include the incidence of adverse drug reactions (ADRs) and adverse events (AEs); 1-year patient and graft survival rates; TAC morning and evening trough concentrations and the AUC fluctuation index; the degree of fluctuation in AUC0-24; the degree of fluctuation in calcineurin (CN) activity; the trough concentration-to-daily dose ratio (C0/D); TAC intrapatient variability (IPV); and the number of dose adjustments. In addition, we will explore the correlation between biomarkers-including metabolomics, lipidomics, and gut microbiota-and TAC chronopharmacokinetic characteristics, and, depending on the data, perform a pharmacoeconomic evaluation. The results of this study will provide prospective evidence for chronopharmacokinetic model-guided precision dosing of TAC and for routine clinical monitoring.
2,121 studies on the registry are indexed under Kidney Failure, Chronic; 264 are open to participants now.
This study's planned enrollment of 100 is above the median of 55 across 1,582 interventional studies indexed under Kidney Failure, Chronic.
Browse Kidney Failure, Chronic studies →The First Affiliated Hospital of Guangzhou Medical University is the lead sponsor of 165 studies on the registry; 67 are open to participants now.
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Exclusion Criteria:
Renal transplant recipients receive twice-daily immediate-release tacrolimus with individualized chronotherapy-adjusted dosing (lower morning dose, higher evening dose).
Drug: Chronotherapy-based individualized low-morning high-evening tacrolimus dosing
Renal transplant recipients receive standard twice-daily immediate-release tacrolimus with equal morning and evening doses.
Drug: conventional dosing regimen
Dosing regimen with unequal morning-evening doses guided by a chronopharmacokinetic model
Conventional twice-daily equal-dose tacrolimus dosing regimen
Incidence of acute rejection (biopsy-proven or clinically diagnosed).
Renal-function tests are conducted, and renal allograft biopsy is carried out if needed
Time frame: Within one year subsequent to subject enrolment
Change in graft renal function (eGFR, calculated using the Cockcroft-Gault equation)
The Cockcroft-Gault equation is used for eGFR computation
Time frame: Within one year subsequent to subject enrolment
Documents are hosted by the registry — open the source record to download them.
Plan to share: No
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
This study is not yet recruiting, as verified in Oct 2026. You cannot join it, but the record below documents what was studied.
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The First Affiliated Hospital of Guangzhou Medical University →