Effect of Azole/Echinocandin Use on Tacrolimus Pharmacokinetics

Sponsor

LI YAN (Other)

Overall Status

Completed

CT.gov ID

NCT06044558

Collaborator

(none)

507

Enrollment

Location

Actual Duration (Months)

56.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this observational study is to analyze the extent and characteristics of drug interactions (focusing on azole antifungals and echinocandins) and genetic polymorphisms on tacrolimus blood concentrations in renal transplant recipients in order to provide a reference for the appropriate adjustment of tacrolimus dosing regimen to reduce the incidence of adverse drug reactions and rejection, and to improve the survival of transplanted kidneys.

Condition or Disease	Intervention/Treatment	Phase
Kidney Transplant Patients	Drug: Combined with voriconazole Drug: Combined with caspofungin Drug: Tacrolimus-alone treatment

Detailed Description

In this study, we investigated the effects of CYP3A5 and CYP2C19 gene polymorphisms on the trough concentration of tacrolimus after renal transplantation in recipients who were on a tacrolimus-based immunosuppressive regimen (tacrolimus + mescaline + glucocorticosteroid) after their first renal transplantation; we investigated the effects of antifungal drugs on the trough concentration of tacrolimus, and we also analyzed the effects of genetic factors on the drug-drug interactions between antifungal drugs and tacrolimus, with the aim of providing a basis of reference for the rational use of tacrolimus and antifungal drugs in the clinic.

Study Design

Study Type:

Observational

Actual Enrollment :

507 participants

Observational Model:

Cohort

Time Perspective:

Retrospective

Official Title:

Effect of Azole/Echinocandin Use on Tacrolimus Pharmacokinetics in Kidney Transplant Recipients

Actual Study Start Date :

Sep 1, 2022

Actual Primary Completion Date :

Jan 1, 2023

Actual Study Completion Date :

Jun 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Combined with voriconazole group Methylprednisolone sodium succinate was administered intravenously the day after transplantation at an initial dose of 500 mg/day, with the dose being tapered evenly to 40 mg/day during the first week. During the second week, methylprednisolone tablets were administered continuously at a dose of 40 mg/day, after which the dose was tapered to 16 mg/day as a maintenance dose. Immunosuppression was maintained with oral mycophenolate sodium 720 mg twice daily. For renal transplant patients, the initial oral tacrolimus dose should be 0.15 - 0.30 mg/kg per day divided into morning and evening doses. The starting dose of voriconazole should be 400 mg twice a day, which should be changed to 200 mg twice a day from the next day as a maintenance dose.	Drug: Combined with voriconazole Renal transplant patients taking tacrolimus-based triple immunotherapy and voriconazole drug combination. Other Names: tacrolimus methylprednisolone sodium succinate mycophenolate sodium
Combined with caspofungin group Methylprednisolone sodium succinate was administered intravenously the day after transplantation at an initial dose of 500 mg/day, with the dose being tapered evenly to 40 mg/day during the first week. During the second week, methylprednisolone tablets were administered continuously at a dose of 40 mg/day, after which the dose was tapered to 16 mg/day as a maintenance dose. Immunosuppression was maintained with oral mycophenolate sodium 720 mg twice daily. For renal transplant patients, the initial oral tacrolimus dose should be 0.15 - 0.30 mg/kg per day divided into morning and evening doses. The dosage of caspofungin was 70 mg intravenous injection once on the first day after surgery and 50 mg intravenous injection once a day starting from the second day.	Drug: Combined with caspofungin Renal transplant patients taking a combination of tacrolimus-based triple immunotherapy and caspofungin drugs. Other Names: tacrolimus methylprednisolone sodium succinate mycophenolate sodium
Tacrolimus-alone treatment group Methylprednisolone sodium succinate was administered intravenously the day after transplantation at an initial dose of 500 mg/day, with the dose being tapered evenly to 40 mg/day during the first week. During the second week, methylprednisolone tablets were administered continuously at a dose of 40 mg/day, after which the dose was tapered to 16 mg/day as a maintenance dose. Immunosuppression was maintained with oral mycophenolate sodium 720 mg twice daily. For renal transplant patients, the initial oral tacrolimus dose should be 0.15 - 0.30 mg/kg per day divided into morning and evening doses.	Drug: Tacrolimus-alone treatment Renal transplant patients treated with tacrolimus-based triple immunotherapy alone Other Names: methylprednisolone sodium succinate mycophenolate sodium

Arm

Intervention/Treatment

Combined with voriconazole group

Methylprednisolone sodium succinate was administered intravenously the day after transplantation at an initial dose of 500 mg/day, with the dose being tapered evenly to 40 mg/day during the first week. During the second week, methylprednisolone tablets were administered continuously at a dose of 40 mg/day, after which the dose was tapered to 16 mg/day as a maintenance dose. Immunosuppression was maintained with oral mycophenolate sodium 720 mg twice daily. For renal transplant patients, the initial oral tacrolimus dose should be 0.15 - 0.30 mg/kg per day divided into morning and evening doses. The starting dose of voriconazole should be 400 mg twice a day, which should be changed to 200 mg twice a day from the next day as a maintenance dose.

Drug: Combined with voriconazole

Renal transplant patients taking tacrolimus-based triple immunotherapy and voriconazole drug combination.

Other Names:

tacrolimus

methylprednisolone sodium succinate

mycophenolate sodium

Combined with caspofungin group

Methylprednisolone sodium succinate was administered intravenously the day after transplantation at an initial dose of 500 mg/day, with the dose being tapered evenly to 40 mg/day during the first week. During the second week, methylprednisolone tablets were administered continuously at a dose of 40 mg/day, after which the dose was tapered to 16 mg/day as a maintenance dose. Immunosuppression was maintained with oral mycophenolate sodium 720 mg twice daily. For renal transplant patients, the initial oral tacrolimus dose should be 0.15 - 0.30 mg/kg per day divided into morning and evening doses. The dosage of caspofungin was 70 mg intravenous injection once on the first day after surgery and 50 mg intravenous injection once a day starting from the second day.

Drug: Combined with caspofungin

Renal transplant patients taking a combination of tacrolimus-based triple immunotherapy and caspofungin drugs.

Other Names:

tacrolimus

methylprednisolone sodium succinate

mycophenolate sodium

Tacrolimus-alone treatment group

Drug: Tacrolimus-alone treatment

Renal transplant patients treated with tacrolimus-based triple immunotherapy alone

Other Names:

methylprednisolone sodium succinate

mycophenolate sodium

Outcome Measures

Primary Outcome Measures

The C0/D values of tacrolimus [2015.01.01-2023.04.01]
Body weight is in kilograms, D values are in mg/d, and the combination of body weight and D is the body weight-corrected D value in mg/kg/d, with a range of 0.15-0.30 mg/kg/d. The C0 for tacrolimus is in ng/ml, with a range of 5-15 ng/ml, and the combination of the C0 and body weight-corrected D values is the C0/D value, reported as (ng/ml)/(mg /kg/d) is reported.

Secondary Outcome Measures

The D values of tacrolimus [2015.01.01-2023.04.01]
Body weight was expressed in kilograms, D values were expressed in mg/d, and body weight and D were combined to give body weight-corrected D values in mg/kg/d, ranging from 0.15 to 0.30 mg/kg/d.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients with first kidney transplantation and intact CYP3A5 genotype;
Renal transplant recipients taking a tacrolimus-based triple immunosuppressive regimen (tacrolimus + sodium mescaline enteric-coated tablets + glucocorticoids) postoperatively;
Age ≥ 18 years.

Exclusion Criteria:

Missing and incomplete clinical information and postoperative follow-up data;
Multi-organ combined transplantation and secondary transplantation;
Postoperative simultaneous joint application of other drugs that affect the blood concentration of tacrolimus or voriconazole or caspofungin (e.g. pentoxifylline capsules, rifampicin, etc.);
Severe impairment of liver function or severe gastrointestinal diseases, gastrointestinal resection surgery, malabsorption syndrome;
Pregnant and lactating women;
Recipients with significant rejection of the transplanted organ or death due to other reasons within 1~2 months after surgery;
Poor compliance and accuracy of results (e.g., irregular blood collection times).