Study of Pharmacogenomic-Guided Tacrolimus Dosing and Monitoring in Kidney Transplant Recipients

NCT03020589 | Completed Phase 4 Results FDA Drug

• 1 other identifier: 16-2073
• Study Type: interventional
• Target: 97
• Locations: 1 country
• Sites: 1

Brief Summary

Objective: Investigate the direct correlation of CYP3A5 genotype with tacrolimus trough levels and clinical outcomes. The primary endpoint of this study is to evaluate the proportion of patients reaching target levels (8-10 ng/mL) on Day 3 and Day 7 after kidney transplantation.

Conditions

Renal Transplant

Keywords

Renal Transplant; Tacrolimus; UNC; Phase IV

Outcome Measures

Primary Outcomes (2)

• Proportion of Patients Reaching Target Tacrolimus Levels (8-10 ng/mL) on Day 3 After Kidney Transplantation

  Day 3 after transplantation

• Proportion of Patients Reaching Target Tacrolimus Levels (8-10 ng/mL) on Day 7 After Kidney Transplantation

  Day 7 after transplantation

Secondary Outcomes (5)

• Number of Events of Biopsy Proven Acute Rejection (BPAR)

  first 3 months (Days 0 through 90), 91-180, and 181-365 days after transplantation

• Tacrolimus Level

  4 months

• Mean Number of Dose Adjustments and/or Drug Alterations

  12 months

• Percent of Participants With Chronic Renal Impairment by eGFR Category

  12 months

• Number of Adverse Outcomes

  12 months

Other Outcomes (1)

• Direct and Indirect Costs

  12 months

Study Arms (2)

CYP3A5 based tacrolimus dosing

EXPERIMENTAL

Subjects in this treatment arm will receive initial tacrolimus based on their genotype i.e., CYP3A5\*1/\*1 and CYP3A5\*1/\*3 (Expressers) will receive the initial tacrolimus dose of 0.2 mg/kg/day, with maximum of 20 mg/day in 2 divided doses. For CYP3A5\*3/\*3 (Non-Expressers), the subjects will receive initial tacrolimus dose of 0.1 mg/kg/day in 2 divided doses.

Drug: Tacrolimus

Control

NO INTERVENTION

Subjects in the prospective control group will receive standard tacrolimus dosing as recommended per package insert and will not be dosed based on their genotype. Similarly, subjects that underwent renal transplant after 2010 and received standard tacrolimus dosing (per package insert) will serve as historical controls.

Interventions

Tacrolimus DRUG

See description in arm/group sections

Also known as: Prograf, Advagraf

CYP3A5 based tacrolimus dosing

Eligibility Criteria

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

You may qualify if:

• All new kidney transplant recipients aged 18 to 65 years who are admitted at UNC-CH and provided informed consent will be included in this study.

You may not qualify if:

• Recipients who did not consent to participate in the study.
• Highly sensitized patients (ie, pretransplant T or B cell flow crossmatch positive)
• Recipients of ABO incompatible kidney transplant
• Recipients with preformed donor-specific antibodies (DSA)
• Human Leukocyte Antigen (HLA) identical kidney transplant
• Recipients of non-kidney transplant
• Recipients of repeat transplant if they are on immunosuppression at the time of transplant
• Patients using medications that have known pharmacokinetic (PK) drug interaction with tacrolimus
• Patients in whom tacrolimus therapy is contraindicated

Sponsors & Collaborators

• University of North Carolina, Chapel Hill: lead

Study Sites (1)

Univeristy of North Carolina

Chapel Hill, North Carolina, 27514, United States

Location

MeSH Terms

Interventions

Tacrolimus

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Results Point of Contact

• Title: Robert Dupuis, PharmD
• Organization: University of North Carolina at Chapel Hill

re_dupuis@unc.edu

919-966-6194

Study Officials

• Alexander Toledo, MD

  University of North Carolina, Chapel Hill

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 11, 2017
• First Posted: January 13, 2017
• Study Start: February 6, 2017
• Primary Completion: July 31, 2021
• Study Completion: June 28, 2022
• Last Updated: June 26, 2023
• Results First Posted: July 21, 2022

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)