Effect of Azole/Echinocandin Use on Tacrolimus Pharmacokinetics

NCT ID: NCT06044558

Last Updated: 2023-09-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

507 participants

Study Classification

OBSERVATIONAL

Study Start Date

2022-09-01

Study Completion Date

2023-06-01

Brief Summary

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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.

Detailed Description

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In this study, investigators 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; investigators investigated the effects of antifungal drugs on the trough concentration of tacrolimus, and investigators 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.

Conditions

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Kidney Transplant Patients

Study Design

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Observational Model Type

COHORT

Study Time Perspective

RETROSPECTIVE

Study Groups

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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.

Combined with voriconazole

Intervention Type DRUG

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

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.

Combined with caspofungin

Intervention Type DRUG

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

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.

Tacrolimus-alone treatment

Intervention Type DRUG

Renal transplant patients treated with tacrolimus-based triple immunotherapy alone

Interventions

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Combined with voriconazole

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

Intervention Type DRUG

Combined with caspofungin

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

Intervention Type DRUG

Tacrolimus-alone treatment

Renal transplant patients treated with tacrolimus-based triple immunotherapy alone

Intervention Type DRUG

Other Intervention Names

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tacrolimus methylprednisolone sodium succinate mycophenolate sodium tacrolimus methylprednisolone sodium succinate mycophenolate sodium methylprednisolone sodium succinate mycophenolate sodium

Eligibility Criteria

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Inclusion Criteria

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

Exclusion Criteria

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

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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LI YAN

OTHER

Sponsor Role lead

Responsible Party

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LI YAN

director

Responsibility Role SPONSOR_INVESTIGATOR

Locations

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Shandong Provincial Qianfoshan Hospital

Jinan, Shandong, China

Site Status

Countries

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China

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

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QFS-LY-2023-TAC-001

Identifier Type: -

Identifier Source: org_study_id

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