Extended Release Tacrolimus vs. Twice-Daily Tacrolimus
Condition: End Stage Renal Disease; Rejection of Renal Transplant
MeSH terms: Kidney Failure, Chronic
Study type: Interventional
Phase: Phase 3

Summary: 
      The overall aim of the study is to prospectively investigate the impact of two maintenance
      calcineurin inhibitor immunosuppressive regimens: once-daily extended release tacrolimus and
      twice-daily tacrolimus on subpopulations of T and B cells and alloreactive T cells as well as
      on renal allograft function.
    

Detailed description: 
      Kidney transplantation is the treatment of choice for most patients with end-stage renal
      disease. Lifelong immunosuppressive therapies are required to prevent organ rejection.
      However, long term exposure to immunosuppressive therapy after kidney transplantation can
      place patients at risk for multiple adverse events. The optimal immunosuppressive therapy is
      not well established. Tacrolimus, a calcineurin inhibitor (CNI) is highly effective in
      preventing acute rejection after organ transplantation (2). It is used as part of the
      immunosuppression regimen for the majority of kidney and liver transplant recipients (3).
      However, treatment with current formulation of Tacrolimus generates high peaks and low
      troughs in drug concentrations in the blood. It is known that high exposure to CNI is
      associated with renal toxicities and adverse events (4). New once-daily dosage formulations
      are now developed with the hope of minimizing side effects while maintaining excellent
      outcomes (5-8).

      LCP-Tacro (Envarsus® XR, Veloxis Pharmaceuticals), a new once-daily formulation of
      tacrolimus, was approved by the FDA in 2015 for conversion from twice-daily tacrolimus in
      kidney transplant recipients. It is a prolonged-release tacrolimus formulation, utilizing a
      MeltDose drug delivery technology designed to improve the bioavailability of drugs with low
      water solubility (1). Recent clinical data demonstrated that once-daily LCP-Tacro has
      improved pharmacokinetic bioavailability, rapid achievement of therapeutic trough levels,
      less fluctuation and swing in whole blood concentration, non-inferior efficacy and similar
      safety, with lower tacrolimus dose than other tacrolimus formulations.

      The target population is adult recipients of immediately functioning living and deceased
      donor renal allografts. Immediate function will be defined as the absence of the need for
      hemodialysis in the first week following renal transplantation.

      Prospective randomized single center open label study of 2 groups of kidney transplant
      patients

        -  Group 1 : standard of care (SOC) control group will receive tacrolimus twice-daily
           (n=25)

        -  Group 2 : LCP-Tacro (Envarsus® XR) group will receive LCPT tablets once daily (n=25)
    

Intervention name(s): Tacrolimus; Tacrolimus Extended Release Oral Tablet [Envarsus]
Intervention type(s): Drug; Drug
Intervention description(s): immunosuppressive agent tacrolimus, given twice-daily; immunosuppressive agent extended-release tacrolimus, given once daily
Other intervention name(s): LCP-tacro
Intervention MeSH terms: Tacrolimus
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: immunosuppression