| Registry | NCT07877103 |
|---|---|
| Status | Not yet recruiting |
| Phase | Phase 4 |
| Study type | Interventional; randomized, parallel, masking: none, treatment |
| Enrollment | 100 (Estimated) |
| Sponsor | The First Affiliated Hospital of Guangzhou Medical University (Other); collaborators: Second Affiliated Hospital of Guangzhou Medical University, The Third Affiliated Hospital of Guangzhou Medical University, Guangdong Provincial Hospital of Traditional Chinese Medicine, Zhujiang Hospital |
| Conditions | End-Stage Renal Disease |
| Interventions | Chronotherapy-based individualized low-morning high-evening tacrolimus dosing, conventional dosing regimen (Drug) |
| Dates | start 2026-10-25 (estimated), primary completion 2027-12-30 (estimated), completion 2028-12-30 (estimated), first posted 2026-10-16, last updated 2026-10-16 |
| Locations | 1 site in China |
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All trials for End-Stage Renal Disease All trials of Chronotherapy-based individualized low-morning high-evening tacrolimus dosing All trials of conventional dosing regimen
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.
| Arm | Type | Interventions | Description |
|---|---|---|---|
| Chronotherapy-based individualized low-morning high-evening tacrolimus dosing group | Experimental | Drug: Chronotherapy-based individualized low-morning high-evening tacrolimus dosing | Renal transplant recipients receive twice-daily immediate-release tacrolimus with individualized chronotherapy-adjusted dosing (lower morning dose, higher evening dose). |
| Conventional equal twice-daily tacrolimus dosing group | Active comparator | Drug: conventional dosing regimen | Renal transplant recipients receive standard twice-daily immediate-release tacrolimus with equal morning and evening doses. |
Sex: All, ages: 18 Years to 70 Years
Inclusion Criteria: * Sex not restricted, age 18-70 years (inclusive) * First living-donor or deceased-donor kidney transplantation * For deceased-donor transplantation, kidneys from donation after brain death (DBD) * ABO blood type compatibility between donor and recipient * Negative panel reactive antibody (PRA) result within 6 months before surgery * Post-transplant immunosuppressive regimen must be the triple regimen of TAC + mycophenolate mofetil (MMF)/mycophenolate sodium (MPS) + glucocorticoids * More than 3 months after kidney transplantation, with stable graft function * Stable TAC dose regimen and Ctrough results, and stable concomitant medication regimen * Voluntarily participate in the clinical study, fully understand the study and voluntarily sign the informed consent form (ICF), and be able to complete all study procedures Exclusion Criteria: * Multiple organ combined transplantation * History of prior organ transplantation other than the kidney * History of acute rejection after transplantation, or currently receiving treatment for acute rejection * Evidence of active systemic or localized infection * Currently severe diarrhea, vomiting, active peptic ulcer, or other gastrointestinal diseases affecting TAC absorption * Allergy to TAC or its ingredients, or other contraindications precluding the use of TAC * Pregnant women, or women of childbearing potential who plan to become pregnant * Use of strong CYP3A inhibitors or strong inducers within 2 weeks before first dosing, or short-term use during the study * Poor recipient compliance, or other conditions judged by the investigator to make the participant unsuitable for enrollment
| Facility | City | Country | Status |
|---|---|---|---|
| The First Affiliated Hospital of Guangzhou Medical University | Guangzhou, Guangdong | China |