End-Stage Renal DiseasePhase 4NCT07877103
Study on the Safety and Efficacy of a Time-of-Day-Based Individualized Tacrolimus Dosing Regimen in Kidney Transplant Recipients
A Phase 4 study testing Chronotherapy-based individualized low-morning high-evening tacrolimus dosing and conventional dosing regimen in people with End-Stage Renal Disease, run by The First Affiliated Hospital of Guangzhou Medical University at 1 site in China.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- End-Stage Renal Disease
- What is being tested?
- Chronotherapy-based individualized low-morning high-evening tacrolimus dosing and conventional dosing regimen
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 1 siteChina
- Study dates
- 25 Oct 2026to 30 Dec 2028
- Phase
- Phase 4
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site
The First Affiliated Hospital of Guangzhou Medical University
Guangzhou, Guangdong, 511436
Xiaoyou Liu, +8618922217771, liuxy@gzhmu.edu.cn
About this study
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.
Read more
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
Read the detailed description
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.
- Conditions
- End-Stage Renal Disease
- Being tested
- Chronotherapy-based individualized low-morning high-evening tacrolimus dosing, conventional dosing regimen
- Keywords
- kidney transplantation, tacrolimus
- Medical subject headings
- Kidney Failure, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Chronotherapy-based individualized low-morning high-evening tacrolimus dosingDrug
Dosing regimen with unequal morning-evening doses guided by a chronopharmacokinetic model
conventional dosing regimenDrug
Conventional twice-daily equal-dose tacrolimus dosing regimen
| Study group | Role | What they receive |
|---|---|---|
| Chronotherapy-based individualized low-morning high-evening tacrolimus dosing group | Experimental | Renal transplant recipients receive twice-daily immediate-release tacrolimus with individualized chronotherapy-adjusted dosing (lower morning dose, higher evening dose). Receives: Drug: Chronotherapy-based individualized low-morning high-evening tacrolimus dosing |
| Conventional equal twice-daily tacrolimus dosing group | Active comparator | Renal transplant recipients receive standard twice-daily immediate-release tacrolimus with equal morning and evening doses. Receives: Drug: conventional dosing regimen |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of acute rejection (biopsy-proven or clinically diagnosed).
Renal-function tests are conducted, and renal allograft biopsy is carried out if needed
Measured: 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
Measured: Within one year subsequent to subject enrolment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Oct 2026
- Study start25 Oct 2026 (estimated)
- Primary completion30 Dec 2027 (estimated)
- Study completion30 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for End-Stage Renal DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- The First Affiliated Hospital of Guangzhou Medical University
- Sponsor type
- University, hospital or 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
- Responsible party
- Principal investigator, Liu Xiaoyou, The First Affiliated Hospital of Guangzhou Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07877103
- Sponsor's protocol ID
- ES-2024-064-02
- Status last verified
- Oct 2026
- First submitted
- 7 Oct 2026
- Last updated
- 16 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Lloberas N, Grinyo JM, Colom H, Vidal-Alabro A, Fontova P, Rigo-Bonnin R, Padro A, Bestard O, Melilli E, Montero N, Coloma A, Manonelles A, Meneghini M, Fava A, Torras J, Cruzado JM. A prospective controlled, randomized clinical trial of kidney transplant recipients developed personalized tacrolimus dosing using model-based Bayesian Prediction. Kidney Int. 2023 Oct;104(4):840-850. doi: 10.1016/j.kint.2023.06.021. Epub 2023 Jun 28.
PubMed 37391040