Research on individualisation of tacrolimus regimen based on the CYP3A5, MDR1 and PXR genotypes

Completed

Conditions: Renal transplantation/ allograft rejection
Injury, Occupational Diseases, Poisoning
Failure and rejection of transplanted organs and tissues

Registration Number: ISRCTN24376050

Lead Sponsor: Sun Yat-sen University (China)

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: All

Target Recruitment: 500

Inclusion Criteria

1. Adult (both males and females, 18-60 years) recipients underwent single primary renal transplantation in the First Affiliated Hospital of Sun Yat-sen University
2. Only for retrospective study: Used a triple regimen with tacrolimus, mycophenolate mofetil and prednisone after transplantation (Note: In prospective study, patients were enrolled before immunosuppresants were used)
3. Wish to participate in the study
4. Informed consent for the trial

Exclusion Criteria

1. Patients with abnormal hepatic function, serious infection, malignant tumour, and diabetes mellitus
2. Patients with ABO-incompatible renal transplantation
3. Panel reactive antibody (PRA) levels greater than 30% before transplantation
4. Underwent combined organ transplantations
5. Except for diltiazem and SchE, other medication known to affect tacrolimus blood levels, such as verapamil, ketoconazole, itraconazole, erythromycin or clarithromycin was used
6. Allergic history to study medicines
7. During pregnancy or plan to get pregnant during the study period

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
1. Distribution of CYP3A5, MDR1 and PXR polymorphisms in Chinese kidney transplant patients.<br>2. Correlation between dose-adjusted C0, Cmax, AUC0-12 h and CYP3A5, MDR1, PXR polymorphisms when tacrolimus is administered alone or co-administered with diltiazem/ SchE (See Interventions for details of assessment methods).

Secondary Outcome Measures

Name	Time	Method
Comparisons between the pharmacogenetic-guided combination therapy (co-administration with diltiazem or SchE) and conventional therapy:<br>1. The first C0 of tacrolimus after the first dosing of tacrolimus alone or in combination with diltiazem/SchE. The first C0 was measured 72 h (3 days) when plateau concentration can be reached for most people.<br>2. Percentage of out-of-range C0 after the first dosing of tacrolimus alone or in combination with diltiazem/SchE<br>3. Number of dose adjustments made to achieve therapeutic range (5-10 ng/mL)<br>4. Dose requirement to reach therapeutic range(5-10 ng/mL)<br>5. 1-year patient/graft survival and 2-year patient/graft survival<br>6. Incidence of acute rejection, drug-related adverse events and side effects. Duration of follow-up: 2 years. <br>7. Serum creatinine level will be assessed every 2 weeks for the first 3 months post-transplant and monthly thereafter for 2 years