Precision Drug Use of Immunosuppressants Guided by Population Pharmacokinetics/Pharmacodynamic Models in Kidney Transplant Patients

1. Construct a population pharmacokinetic/pharmacodynamic model of tacrolimus in kidney transplant patients, and explore the quantitative relationship between combination drugs and gene polymorphisms on the safety and efficacy of tacrolimus in kidney transplant patients;
2. Based on the established pharmacokinetic/pharmacodynamic model of tacrolimus population in kidney transplant patients, combined with combined drugs, gene polymorphisms and other factors for simulation, predict the steady-state trough concentration and efficacy of tacrolimus in kidney transplant patients taking triple drugs (tacrolimus, mycophenolate mofetil/mycophenol sodium enteric-coated tablets, glucocorticoids), and apply the model to the real world to explore the optimal initial dose and maintenance therapeutic dose of tacrolimus, so as to achieve individualized and precise treatment and guide the rational clinical use of drugs.
3. Clarify the value of precision medicine guided by population pharmacokinetics/pharmacodynamics models in clinical practice.

Study Overview

• Status: Recruiting
• Conditions: Kidney Transplantation; Immunosuppressive Agents

Detailed Description

This is a retrospective study. It is proposed to combine the classical basic principles of pharmacokinetics with mathematical statistical models, and use nonlinear mixed effect model (NONMEM) or other population pharmacokinetics/pharmacodynamics software to establish a population pharmacokinetic/pharmacodynamic model of tacrolimus in kidney transplant patients, and elucidate the combination of drugs, demographic factors, pathophysiological factors, genotype, The quantitative effect of comorbid diseases and drugs on the steady-state trough concentration and efficacy of tacrolimus in kidney transplant patients, so as to realize individualized and precise treatment of kidney transplant patients through model simulation and prediction of steady-state trough concentration and efficacy after taking drugs.

• Study Type: Observational
• Enrollment (Estimated): 120

Contacts and Locations

• Study Contact: Name: Yu Xian; Phone Number: 18512356862; Email: 1clinicaltrial@hospital.cqmu.edu.cn
• Study Contact Backup: Name: Xiang Qiulin; Phone Number: 18716938270; Email: xql1844025147@163.com

Study Locations

• China
  • Chongqing, China
    • Recruiting
    • The Second Affiliated Hospital of Chongqing Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

All of the included population was kidney transplant patients,and all of they used triple immunosuppressant (tacrolimus + mycophenolate mofetil + glucocorticoids) for anti-rejection therapy,the results of laboratory could be collected.

Description

Inclusion Criteria:

• Patients undergoing kidney transplantation for the first time.
• Anti-rejection therapy with triple immunosuppressant (tacrolimus + mycophenolate mofetil + glucocorticoids).

Exclusion Criteria:

• The patient's medication status is unclear and there is a lack of relevant results of laboratory test indicators.
• The patient has undergone multi-organ or combined liver and kidney transplantation or has a history of liver and kidney transplantation.
• Transplantation failure or death.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Drug plasma tough concentrations	The tough concentrations of tacrolimus are as regard as the PK parameters	Blood samples were collected 30minutes before administration
Immune factors levels(CD4+、CD8+、CD4+/CD8+、CD4+%、CD8+%)	The Immune factors levels are as regard as the PD parameters	The Immune factors levels were collected 30minutes before administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical indicators	Incidence of acute rejection,Incidence of tacrolimus adverse reactions and other advers are as regard as the PD parameters	Follow-up after kidney transplantation was 6 months

Collaborators and Investigators

• Sponsor: The Second Affiliated Hospital of Chongqing Medical University

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2022
• Primary Completion (Estimated): July 1, 2024
• Study Completion (Estimated): July 1, 2024

Study Registration Dates

• First Submitted: April 19, 2023
• First Submitted That Met QC Criteria: May 15, 2023
• First Posted (Actual): May 24, 2023

Study Record Updates

• Last Update Posted (Actual): September 13, 2023
• Last Update Submitted That Met QC Criteria: September 12, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Kidney transplantation; Immunosuppressive Agents; Population pharmacokinetics/pharmacodynamics
• Other Study ID Numbers: 2023-50

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No