NCT04225988

Comparison of Tacrolimus Extended-Release (Envarsus XR) to Tacrolimus Immediate-Release in Human Leukocyte Antigen (HLA) Sensitized Kidney Transplant Recipients

A Prospective, Pilot Trial to Compare the Efficacy of Tacrolimus Extended-Release (Envarsus XR) to Tacrolimus Immediate-Release on Suppression of Donor-Specific Antibodies in HLA Sensitized Kidney Transplant Recipients

• Status: Completed
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 20 (actual)
• Sponsor: Cedars-Sinai Medical Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is a randomized, open-label, controlled clinical trial designed to compare clinical outcomes after kidney transplantation using extended-release tacrolimus (Envarsus XR) versus immediate tacrolimus among highly-sensitized kidney transplant recipients. Outcomes to be assessed include the incidence of biopsy-proven acute rejection at 12 months, the presence of de novo and pre-existing donor-specific HLA antibodies, estimated glomerular filtration rate, and the level of donor-derived cell-free DNA.

Detailed description

Extended-release tacrolimus (Envarsus XR) received FDA approval in July, 2015 for the prevention of allograft rejection in kidney transplantation on the basis of two separate phase 3 trials of de novo and stable kidney transplant recipients that demonstrated non-inferiority to immediate-release tacrolimus for the composite outcome of death, graft failure, biopsy-proven acute rejection, or loss to follow-up within 12 months (1,2). Both phase 3 trials involved mostly low immunologic risk recipients with follow-up to one year. It has been previously shown that the incidence of de novo donor-specific antibodies (DSA) in the first year after kidney transplant in low-immunologic patients is low, developing in only 2%-11% of unsensitized de novo kidney transplant recipients (3-6). Donor-specific antibodies (DSA) are the primary mediator of antibody-mediated rejection and their development after transplant is a major risk factor for late allograft failure (7). It is now believed that antibody-mediated rejection is the most common cause of late allograft failure (8,9). However, neither of the two phase 3 trials were able to adequately assess the effect of Envarsus XR on the development of donor specific antibodies and therefore, the efficacy of Envarsus XR in higher immunologic risk recipients is not known. Therefore, a comparative study of extended- and immediate-release tacrolimus in highly-sensitized recipients is warranted. This is a randomized, open-label, controlled clinical trial designed to compare clinical outcomes after kidney transplantation using extended-release tacrolimus (Envarsus XR) versus immediate tacrolimus among highly-sensitized kidney transplant recipients. Twenty patients will be enrolled, with ten assigned to each study arm. Outcomes to be assessed include the incidence of biopsy-proven acute rejection at 12 months, the presence of de novo and pre-existing donor-specific HLA antibodies, estimated glomerular filtration rate, and the level of donor-derived cell-free DNA.

Conditions

• Kidney Transplant Rejection

Interventions

Type	Name	Description
DRUG	Extended-release tacrolimus	Patients will receive the extended-release formulation of tacrolimus for maintenance immunosuppression.
DRUG	Immediate-release tacrolimus	Patients will receive the immediate-release formulation of tacrolimus for maintenance immunosuppression.

Timeline

• Start date: 2020-01-09
• Primary completion: 2023-07-11
• Completion: 2023-07-11
• First posted: 2020-01-13
• Last updated: 2024-07-10
• Results posted: 2024-07-10

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study