Effect of Azole/Echinocandin Use on Tacrolimus Pharmacokinetics

NCT06044558 | Completed

• 1 other identifier: QFS-LY-2023-TAC-001
• Study Type: observational
• Target: 507
• Locations: 1 country
• Sites: 1

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.

Conditions

Kidney Transplant Patients

Keywords

tacrolimus; voriconazole; C0/D; CYP3A5; drug-drug interactions; caspofungin; kidney transplant

Outcome Measures

Primary Outcomes (1)

• The C0/D values of tacrolimus

  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.

  2015.01.01-2023.04.01

Secondary Outcomes (1)

• The D values of tacrolimus

  2015.01.01-2023.04.01

Study Arms (3)

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

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

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

Interventions

Combined with voriconazole DRUG

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

Also known as: tacrolimus, methylprednisolone sodium succinate, mycophenolate sodium

Combined with voriconazole group

Combined with caspofungin DRUG

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

Also known as: tacrolimus, methylprednisolone sodium succinate, mycophenolate sodium

Combined with caspofungin group

Tacrolimus-alone treatment DRUG

Renal transplant patients treated with tacrolimus-based triple immunotherapy alone

Also known as: methylprednisolone sodium succinate, mycophenolate sodium

Tacrolimus-alone treatment group

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The study included patients who underwent renal transplantation at our hospital between 01.01.2015 and 04.01.2023 and were divided into the co-voriconazole group, co-carbophenazole group and tacrolimus alone group according to co-administration.

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• LI YAN: lead

Study Sites (1)

Shandong Provincial Qianfoshan Hospital

Jinan, Shandong, China

Location

MeSH Terms

Interventions

Voriconazole; Tacrolimus; Methylprednisolone Hemisuccinate; Mycophenolic Acid; Caspofungin

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Macrolides; Lactones; Organic Chemicals; Methylprednisolone; Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids; Lipopeptides; Peptides; Amino Acids, Peptides, and Proteins; Echinocandins; Peptides, Cyclic

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: director

Study Record Dates

• First Submitted: August 28, 2023
• First Posted: September 21, 2023
• Study Start: September 1, 2022
• Primary Completion: January 1, 2023
• Study Completion: June 1, 2023
• Last Updated: September 28, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)