Clinical Trial: Efficacy and Safety of Tacrolimus Versus Mycophenolate in Lupus Nephritis

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: A Randomized Open-label Study to Evaluate the Efficacy and Safety of Tacrolimus and Corticosteroids in Comparison With Mycophenolate Mofetil and Corticosteroids in Subjects With Class III/IV±V

Brief Summary: Prospective, randomized, parallel-group controlled, open-label, international (Asian) multicenter, comparison of corticosteroids combined with TAC and corticosteroids combined with MMF.

Detailed Summary: There is accumulating evidence that tacrolimus (TAC) could serve as an effective medication for the treatment of lupus nephritis (LN). TAC is a calcineurin inhibitor, which is a key component in first-line combination immunosuppressive regimens after kidney transplantation, based on its proven efficacy in the prevention and treatment of allograft rejection and acceptable tolerability profile. Although it primarily targets T lymphocyte activation, its immunosuppressive actions encompass multiple immune response pathways due to the complex interactions between different cellular and soluble immune mediators. Moreover, the effect of calcineurin inhibitors on podocyte morphology and function, independent of their immunosuppressive effect, has translated into therapeutic efficacy in the treatment of proteinuric glomerular diseases such as membranous nephropathy and focal segmental glomerulosclerosis. Recent data from short-term studies showed that combination immunosuppressive regimens that included TAC and corticosteroids with or without mycophenolate mofetil (MMF) appeared at least as effective as other standard-of-care treatments for Class III/IV±V LN, and the inclusion of TAC might lead to more effective suppression of proteinuria. There is also preliminary data on its favorable tolerability when used as long-term maintenance treatment. This study aims to examine the role of TAC combined with corticosteroids, in comparison with the most commonly used standard-of-care treatment MMF plus corticosteroids, in the management of lupus nephritis.
Sponsor: The University of Hong Kong

Current Primary Outcome: Efficacy of combined corticosteroids and TAC compared to combined corticosteroids and MMF in achieving sustained renal response (RR) in patients with active lupus nephritis [Class III/IV±V (LN)] [ Time Frame: 96 weeks ]

Sustained RR defined as satisfying all of the following criteria:

  1. proteinuria improved by >50% compared with baseline
  2. 24-hr urine protein <1 g
  3. serum creatinine not higher than 15% above baseline level
  4. no occurrence of disease flare, defined as receiving 'rescue' increase of immunosuppressive therapy with any one of the following - requiring increase of prednisolone (or prednisone, or equivalent) dose to above 15 mg/D for 4 weeks or longer, change of originally assigned immunosuppressive agent, or addition of immunosuppressive medications prohibited in protocol


Original Primary Outcome: Same as current

Current Secondary Outcome:

Original Secondary Outcome:

Information By: The University of Hong Kong

Dates:
Date Received: December 5, 2015
Date Started: September 2015
Date Completion: August 2019
Last Updated: October 24, 2016
Last Verified: October 2016