Simplified IMmunosuppressive Protocol Utilizing Low Dose EnvarsusXR

NCT ID: NCT04773392

Last Updated: 2025-11-10

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE4

Total Enrollment

20 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-11-23

Study Completion Date

2024-02-23

Brief Summary

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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

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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

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Kidney Transplantation Kidney Transplant Rejection

Keywords

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tacrolimus envarsus XR kidney transplant rejection immunosuppressive agents renal transplant

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

This is an open-label, randomized, prospective clinical trial. Patients will be screened prior to surgery and randomized 1:1 to each arm.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Twice-daily Regimen

Twice-daily regimen of immediate release tacrolimus, mycophenolate mofetil (MMF)/mycophenolic acid (MPA) plus daily methylprednisolone or prednisone.

Group Type ACTIVE_COMPARATOR

Twice-daily Tacrolimus

Intervention Type DRUG

Within 48 hours of transplantation, immediate release tacrolimus (IRT) (0.1 mg/kg /day) will be administered twice a day.

Induction Immunosuppression with Basiliximab or Rabbit Anti Thymoglobulin (rATG)

Intervention Type DRUG

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.

Methylprednisolone, prednisone

Intervention Type DRUG

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.

Mycophenolate mofetil (MMF) or Mycophenolic acid (MPA)

Intervention Type DRUG

Mycophenolate mofetil (MMF) (up to 1000mg) or Mycophenolic acid (MPA) (up to 720mg) will be administered twice a day.

Once-daily Regimen

Once-daily regimen of Envarsus, azathioprine plus methylprednisolone or prednisone.

Group Type ACTIVE_COMPARATOR

Once-daily envarsus XR

Intervention Type DRUG

Within 48 hours of transplantation, Envarsus XR (0.13mg/kg/day) will be administered once a day.

Induction Immunosuppression with Basiliximab or Rabbit Anti Thymoglobulin (rATG)

Intervention Type DRUG

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.

Methylprednisolone, prednisone

Intervention Type DRUG

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.

Azathioprine

Intervention Type DRUG

Azathioprine (1-3 mg/kg) will be administered once a day.

Interventions

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Twice-daily Tacrolimus

Within 48 hours of transplantation, immediate release tacrolimus (IRT) (0.1 mg/kg /day) will be administered twice a day.

Intervention Type DRUG

Once-daily envarsus XR

Within 48 hours of transplantation, Envarsus XR (0.13mg/kg/day) will be administered once a day.

Intervention Type 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.

Intervention Type 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.

Intervention Type 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.

Intervention Type DRUG

Azathioprine

Azathioprine (1-3 mg/kg) will be administered once a day.

Intervention Type DRUG

Other Intervention Names

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immediate release tacrolimus extended releated tacrolimus Simulect, ATG Steroids Twice a day anti-metabolite Once a day anti-metabolite

Eligibility Criteria

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Inclusion Criteria

* De- Novo Kidney transplant patients between 18 and 85 years old
* Cold ischemia time (CIT) \< 24 hours for 3-6 HLA mismatches between donor and recipient and CIT \>24 hours for HLA mismatch of less than 3 between donor and recipient
* Most recent pre-transplant cPRA (calculated panel reactive antibody) ≤ 20%

Exclusion Criteria

* Repeat kidney transplant recipients
* cPRA \>20%
* rATG (rabbit anti-thymocyte globulin) induction \>6mg/kg at time of induction
* Crossmatches deemed positive by accepting physician
* Presence of pre-formed anti-HLA (anti-Human Leukocyte Antigen) DSA (Donor-Specific Antibody) as defined by MFI (mean fluorescence intensity) approaching 3000 using flow cytometry/Luminex-based, specific anti-HLA antibody testing.
* Receipt of desensitization protocols
* History of skin cancer
* Recipient of multi-organ or dual kidney transplants
* For any condition, in which the investigator's opinion makes the subject unsuitable for study
Minimum Eligible Age

18 Years

Maximum Eligible Age

85 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Veloxis Pharmaceuticals

INDUSTRY

Sponsor Role collaborator

University of Southern California

OTHER

Sponsor Role lead

Responsible Party

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Santhi Voora

Assistant Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Santhi Voora, MD

Role: PRINCIPAL_INVESTIGATOR

University of Southern California

Locations

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University of Southern California

Los Angeles, California, United States

Site Status

Countries

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United States

References

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Park SI, Felipe CR, Pinheiro-Machado PG, Garcia R, Fernandes FB, Casarini DE, Tedesco-Silva H Jr, Medina-Pestana JO. Tacrolimus pharmacokinetic drug interactions: effect of prednisone, mycophenolic acid or sirolimus. Fundam Clin Pharmacol. 2009 Feb;23(1):137-45. doi: 10.1111/j.1472-8206.2008.00644.x.

Reference Type BACKGROUND
PMID: 19267777 (View on PubMed)

Dalal P, Shah G, Chhabra D, Gallon L. Role of tacrolimus combination therapy with mycophenolate mofetil in the prevention of organ rejection in kidney transplant patients. Int J Nephrol Renovasc Dis. 2010;3:107-15. doi: 10.2147/ijnrd.s7044. Epub 2010 Aug 4.

Reference Type BACKGROUND
PMID: 21694936 (View on PubMed)

Kulich KR, Madisch A, Pacini F, Pique JM, Regula J, Van Rensburg CJ, Ujszaszy L, Carlsson J, Halling K, Wiklund IK. Reliability and validity of the Gastrointestinal Symptom Rating Scale (GSRS) and Quality of Life in Reflux and Dyspepsia (QOLRAD) questionnaire in dyspepsia: a six-country study. Health Qual Life Outcomes. 2008 Jan 31;6:12. doi: 10.1186/1477-7525-6-12.

Reference Type BACKGROUND
PMID: 18237386 (View on PubMed)

Troster AI, Pahwa R, Fields JA, Tanner CM, Lyons KE. Quality of life in Essential Tremor Questionnaire (QUEST): development and initial validation. Parkinsonism Relat Disord. 2005 Sep;11(6):367-73. doi: 10.1016/j.parkreldis.2005.05.009.

Reference Type BACKGROUND
PMID: 16103000 (View on PubMed)

Related Links

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Other Identifiers

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HS-18-00513

Identifier Type: -

Identifier Source: org_study_id