Safety and Efficacy of Basiliximab, Delayed Dose Tacrolimus Plus ECMPA (Enteric Coated Mycophenolic Acid) Following Liver Transplantation
Condition: Liver Transplantation
Study type: Interventional
Phase: Phase 4

Summary: 
      This is an investigator initiated study at the University of California, Los Angeles (UCLA)
      funded by Novartis looking at using a combination of immunosuppressive drugs in liver
      transplant patients that are at risk of developing kidney problems. Kidney problems following
      liver transplants is the most problematic issue facing liver transplant patients today.

      This study will generate information in this area of high unmet medical need utilizing
      basiliximab and Myfortic and using a reduced dose of tacrolimus, one of the current standard
      of care medications, after kidney function has normalized.
    

Detailed description: 
      Since basiliximab works on the same receptor system as tacrolimus and has not been shown to
      cause significant adverse effects, such as nephrotoxicity or the cytokine release syndrome,
      the investigators are proposing induction therapy with basiliximab in liver transplant
      patients with concomitant preoperative renal dysfunction. This will combat acute rejection
      and allow the delay of tacrolimus therapy until post-operative day #7. The delay in
      tacrolimus therapy should allow renal function to improve and reduce the chance of continued
      renal dysfunction. Also, the addition of basiliximab to the immunosuppressive regimen should
      allow for a reduction in tacrolimus dose (normal tacrolimus concentrations at UCLA are
      7-10ng/mL. Our goal will be 3-5ng/mL) in the immediate post-transplant period thereby
      reducing the chance of acute and long-term efficacy-limiting adverse effects associated with
      the tacrolimus while maintaining adequate immunosuppression to reduce acute rejection
      episodes. This would be the most convincing prospective randomized study utilizing
      basiliximab as a renal sparing agent in liver transplantation.

      Objectives Primary objectives

      • To evaluate renal recovery/ function following OLT in patients undergoing orthotopic liver
      transplant at 6 and 12 months post-transplant.

      Secondary objectives (comparing the two treatment arms)

        -  To determine the tolerability and adverse event profile during the first year
           post-transplant.

        -  To determine incidence and severity acute rejection episodes

        -  To determine the incidence of death and/or graft failure within the first year
           post-transplant

      Study design The study is a single center prospective randomized trial wherein the
      investigators will have two groups. Patients will be screened and eligible patients will be
      enrolled pre-transplant. Patients will then be randomized at time of transplant to either the
      control or treatment arm. Post transplant laboratory data (chemistry, tacrolimus level and
      liver function tests) will be collected on a daily basis. For the duration of the patients'
      hospital stay (average 2-3 weeks). This will provide the early data set for early post
      operative results. Patients will subsequently be followed on a weekly outpatient basis upon
      discharge as per protocol. During these visits, laboratory data (chemistry, tacrolimus level
      and liver function tests) are also collected and will provide the continued flow of data for
      our follow up analysis. Any evidence of rejection will prompt treatment with rescue therapy
      and if necessary disenrollment from the study.
    

Intervention name(s): Basiliximab; Tacrolimus; Tacrolimus; Mycophenolic Acid
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): Peri-operative 40 mg IV dose within 4 hours of OLT Postoperative 20mg IV dose Day 4; Day #7 post-transplant or when serum creatinine (SCr) < 1.8 mg/dl 6 months to 1 year: 0.03-0.1 mg.kg q12h po to maintain whole blood trough concentration of 3-5ng/mL; Day #1 post-transplant to 6 months: 0.03-0.1mg/kg q12h po to maintain whole blood trough concentration of 7-10 ng/mL + 6 months to 1 year: maintain whole blood trough concentration of 5-8ng/mL; Enteric coated mycophenolic acid 360-720 mg po bid
Other intervention name(s): Simulect; Prograf; Prograf; Myfortic; Mycophenolate sodium
Intervention MeSH terms: Mycophenolic Acid; Tacrolimus; Basiliximab
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Simulect; Myfortic; Orthotopic liver transplantation (OLT); Renal Dysfunction