Clinical trial NCT06044558: Effect of Azole/Echinocandin Use on Tacrolimus Pharmacokinetics
Official title: Effect of Azole/Echinocandin Use on Tacrolimus Pharmacokinetics in Kidney Transplant Recipients
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Kidney Transplant Patients
Keywords: tacrolimus
voriconazole
C0/D
CYP3A5
drug-drug interactions
caspofungin
kidney transplant
Lead sponsor: Qianfoshan Hospital
Sponsor class: OTHER
First posted: 2023-09-21
Enrollment: 507
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
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.

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.

Detailed description: 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.

Eligibility criteria: 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).

Primary outcomes:
measure: The C0/D values of tacrolimus
timeFrame: 2015.01.01-2023.04.01
Secondary outcomes:
measure: The D values of tacrolimus
timeFrame: 2015.01.01-2023.04.01
Other outcomes:
Locations:
city: Jinan
country: China
facility: Shandong Provincial Qianfoshan Hospital
state: Shandong
Study officials:
References: