NCT04773392

Simplified IMmunosuppressive Protocol Utilizing Low Dose EnvarsusXR

SIMPLE Study: A Prospective and Randomized Trial of a Simplified Immunosuppressive Protocol Utilizing Low Dose EnvarsusXR

• Status: Terminated
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 20 (actual)
• Sponsor: University of Southern California · Academic / Other
• Sex: All
• Age: 18 Years – 85 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study is to determine if the combination of once-daily tacrolimus extended-release (EnvarsusXR) and Azathioprine is non inferior with respect to the composite outcome of acute rejection, graft and patient survival as compared to a combination of twice-daily immediate release tacrolimus and mycophenolate mofetil/mycophenolic acid.

Detailed description

While short-term graft outcomes in kidney transplantation have improved, this requires adherence to a complex medication regimen. The current twice-daily immunosuppressive regimen, immediate release tacrolimus and mycophenolate mofetil/mycophenolic acid, has reduced rejection rates significantly, but frequently cause neurologic and gastrointestinal side effects which impact recipient quality of life. These side effects often require dose adjustments and studies have shown inferior outcomes when multiple changes are made to the immunosuppressive regimen. Furthermore, patients taking twice-daily medications have poorer compliance and yet adherence to these medications is critical to mitigate the risk of allograft rejection. Acute and chronic rejection are important causes of graft failure and patient survival. Immediate release (IR) tacrolimus based immunosuppressive regimens have become the standard of care at most US centers. With the introduction of a once-daily tacrolimus formulation, kidney transplant recipients can now be on a combination regimen (EnvarsusXR and azathioprine) that permits all immunosuppressive medications to be taken once a day instead of twice . Previous studies suggest that therapeutic goals with EnvarsusXR may be achieved at a lower dose than the currently recommended dose. This once a day medication schedule has the potential to simplify the immunosuppressive regimen by reducing adverse side effects and facilitating compliance. The investigators seek to demonstrate that a once-daily regimen, including EnvarsusXR and azathioprine, will be at least equally effective with respect to acute rejection, graft and patient survival as compared to the standard, twice-daily, immediate release tacrolimus and mycophenolate mofetil/mycophenolic acid. The investigators will also assess graft function, medication complications and side effects in each arm.

Conditions

• Kidney Transplantation
• Kidney Transplant Rejection

Interventions

Type	Name	Description
DRUG	Twice-daily Tacrolimus	Within 48 hours of transplantation, immediate release tacrolimus (IRT) (0.1 mg/kg /day) will be administered twice a day.
DRUG	Once-daily envarsus XR	Within 48 hours of transplantation, Envarsus XR (0.13mg/kg/day) will be administered once a day.
DRUG	Induction Immunosuppression with Basiliximab or Rabbit Anti Thymoglobulin (rATG)	Induction immunosuppression with Basiliximab or Rabbit Anti Thymoglobulin (rATG) per protocol. The dose of Basiliximab will be a standard of two 20 mg doses and total rATG will not exceed 6 mg/kg.
DRUG	Methylprednisolone, prednisone	Methylprednisolone intraoperatively (500mg) and immediately post transplantation (200mg on post operative day (POD) #1, 150mg on POD#2, 100mg on POD#3) then oral prednisone (50mg on POD #4, 20mg on POD #5). Oral prednisone will be tapered down to a minimal dose of 5mg within 6 weeks post transplantation.
DRUG	Mycophenolate mofetil (MMF) or Mycophenolic acid (MPA)	Mycophenolate mofetil (MMF) (up to 1000mg) or Mycophenolic acid (MPA) (up to 720mg) will be administered twice a day.
DRUG	Azathioprine	Azathioprine (1-3 mg/kg) will be administered once a day.

Timeline

• Start date: 2021-11-23
• Primary completion: 2024-02-23
• Completion: 2024-02-23
• First posted: 2021-02-26
• Last updated: 2025-11-10

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study