Clinical Trial in Assigning of Tacrolimus Dosage Regimen According to CYP3A5 Genotype in Kidney Transplant Recipients

NCT03173820 | Unknown FDA Drug

• 1 other identifier: KhonKaenU_tacrolimus
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

Kidney transplantation is the most appropriated treatment in end stage renal failure patients in order to improve quality of life. However, patients have to take immunosuppressive drugs to prevent graft rejection. Tacrolimus is the most common immunosuppressive drug used now. However, tacrolimus has narrow therapeutic level and needs regularly therapeutic monitor because of inter-individual variation in dosage regimen. Not only age, body weight and drug interaction but also genetic factor in metabolic pathway of tacrolimus plays an important role in tacrolimus blood level. Previous data showed CYP3A5 genetic polymorphism was significant effect tacrolimus blood level. From previous study showed the mean dose of tacrolimus required for the induction phase was significantly higher (P= 0.006) in the CYP3A5\*1/\*1 group at 0.142±0.050 mg/kg/day than that required by patients who carried either the CYP3A5\*1/\*3 group of 0.097±0.040 mg/kg/day or the CYP3A5\*3/\*3 group of 0.077±0.020 mg/kg/day. Tacrolimus maintenance dose required for CYP3A5\*1/\*1 group of 0.12±0.03 mg/kg/day was 1.3 times higher (P\<0.0001) than used for the CYP3A5\*1/\*3 at 0.09±0.03 mg/kg/day and 2.4 times higher than the CYP3A5\*3/\*3 group of 0.05±0.02 mg/kg/day. Therefore, the investigators plan to investigate a prospective study to determine the clinical outcome of tacrolimus treatment in kidney transplant recipients between genotype guided dosage regimen group and conventional group.

Conditions

Kidney Transplantation

Keywords

tacrolimus; transplantation; CYP3A5; genotype

Outcome Measures

Primary Outcomes (1)

• Mean tacrolimus level

  Proportion of patients whose tacrolimus level were in therapeutic range at day 3 post transplantation

  at day 3 after transplantation

Secondary Outcomes (3)

• Mean tacrolimus level

  at day 1, 3, 5, 7, 14, 30,60, 90, 120, 150 and 180 days post transplantation

• Incidence of delay graft rejection

  day 1- 6 month after transplantation

• Mean GFR level

  at day 7, 14, 30, 60, 90, 120, 150, and 180 days after transplantation

Study Arms (2)

Conventional

PLACEBO COMPARATOR

no genotype of CYP3A5 investigated to adjust tacrolimus dosage regimen

Genetic: Conventional

Genotype guided

ACTIVE COMPARATOR

Use CYP3A5 genotype to adjust dosage regimen for tacrolimus

Genetic: Genotype guided

Interventions

Genotype guided GENETIC

Tacrolimus will be prescribed depend on CYP3A5 genotype. CYP3A5\*1/\*1 patients will receive tacrolimus 0.125 mg/kg/day. CYP3A5\*1/\*3 patients will receive tacrolimus 0.1 mg/kg/day. CYP3A5\*3/\*3 patients will received tacrolimus 0.08 mg/kg/day. Tacrolimus target level for this phase will be 5-8 ng/ml.

Genotype guided

Conventional GENETIC

Tacrolimus will be prescribed 0.1 mg/kg /day for all patients to achieve tacrolimus level 5-8 ng/ml.

Conventional

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Kidney transplantation recipients who
• Age \> 18 year old
• Will have kidney transplantation at Srinagarind hospital, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
• Will have the first kidney transplantation
• Will receive tacrolimus as immunosuppressive to prevent graft rejection
• Will have AST and ALT \< 2 time of normal level, total bilirubin \<1.5 mg/dl and direct bilirubin within normal limited
• Welling to volunteer in this study and sign the inform consent

You may not qualify if:

• Kidney transplantation recipients who
• Refuse to join this study
• Have drug allergy to tacrolimus
• Have Pregnancy and lactating Intervention All renal transplantation waiting list patients will invited to join this study and sign inform consent. The patients who will be enroll to this study, will be drawn the blood for 6 ml to perform CYP3A5 genotype assay.
• Patients who perform kidney transplantation and enrolled to this study will randomly assign in equal number to receive tacrolimus doses as in table 1 hr before transplantation and after transplantation. Tacrolimus blood level, BUN/Cr, will regularly perform on day 1, 3. 4, 5, 7, 14 and 28 during induction phase (1st-4th week after kidney transplantation). Moreover, urine 24 hour for Cr, protein will perform in day 7, 14, 28 after transplantation. The physicians will modify the daily dose of tacrolimus according to their practice in order to achieve target range of trough concentration (5-8 ng/ml). Patients will receive other immunosuppressive such as corticosteroid, mycophenolate mofetil as general practice.
• During maintenance phase (5th-24th week after kidney transplantation) tacrolimus doses will be adjusted as in table 1. Tacrolimus blood level, BUN/Cr and urine 24 hour for Cr and protein will be perform on 5, 8, 12, 16, 20, 24 after transplantation. The physicians will modify the daily dose of tacrolimus according to their practice in order to achieve target range of trough concentration (3-5 ng/ml).

Sponsors & Collaborators

• Khon Kaen University: lead
• National Science and Technology Development Agency, Thailand: collaborator

Study Sites (1)

Faculty of Medicine, Khon Kaen University

Khon Kaen, 40002, Thailand

RECRUITING

MeSH Terms

Interventions

Congresses as Topic

Intervention Hierarchy (Ancestors)

Organizations; Health Care Economics and Organizations

Study Officials

• Suda Vannaprasaht, MD

  Faculty of Medicine, Khon Kaen University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Suda Vannaprasaht, MD

CONTACT

66850104006; sudvan@kku.ac.th

Sirirat Reungjui, MD, PhD

CONTACT

66-43-363664; sirirt_a@kku.ac.th, siriratrj@gmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Department of Medicine

Model Details: genotype guided vs conventional tacrolimus dosage regimen

Study Record Dates

• First Submitted: May 22, 2017
• First Posted: June 2, 2017
• Study Start: April 30, 2015
• Primary Completion: December 31, 2017
• Study Completion: June 30, 2018
• Last Updated: June 2, 2017

Record last verified: 2017-06

Data Sharing

• IPD Sharing: Will not share

Locations

TH (1)