Efficacy and Safety of Concentration-controlled Everolimus to Eliminate or to Reduce Tacrolimus Compared to Tacrolimus in de Novo Liver Transplant Recipients (RAD)


Tracking Information

Start Date  ICMJEJanuary 2008
Estimated Primary Completion DateJanuary 2010   (final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE 
 (submitted: February 22, 2008)
Assessment of renal function by Estimated Glomerular Filtration Rate,eGFR , using abbreviated Modification of Diet in Renal Disease at 12-mths post-transplantation Composite efficacy failure of death,graft loss,or loss to follow-up at 12-mths post-trans.
Original Primary Outcome Measures  ICMJESame as current
Change HistoryComplete list of historical versions of study NCT00622869 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE 
 (submitted: February 22, 2008)
Composite efficacy endpoint of treated biopsy proven acute rejection, graft loss, death or loss to follow-up at 12&24 mths post-transp.Incidence onset diabetes post-transp.
Original Secondary Outcome Measures  ICMJESame as current

Descriptive Information

Brief Title  ICMJEEfficacy and Safety of Concentration-controlled Everolimus to Eliminate or to Reduce Tacrolimus Compared to Tacrolimus in de Novo Liver Transplant Recipients
Official Title  ICMJEA 24 Month, Multicenter, Open-label, Randomized, Controlled Study to Evaluate the Efficacy and Safety of Concentration-controlled Everolimus to Eliminate or to Reduce Tacrolimus Compared to Tacrolimus in de Novo Liver Transplant Recipients
Brief Summary

This trial is designed to address important issues that impact recipients of liver allografts as well as clinicians, ie. renal function, reduction or discontinuation of tacrolimus early post-transplantation, and progression rate of fibrosis in Hepatitis C virus (HCV) positive patients.

Detailed Description 
Study PhasePhase III
Study Type  ICMJEInterventional
Study Design  ICMJETreatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study
Condition  ICMJELiver Transplantation
Intervention  ICMJE
  • Drug: Everolimus
    Tacrolimus elimination arm (low dose tacrolimus until Month 4, then tacrolimus eliminated + everolimus + corticosteroids)
  • Drug: Tacrolimus
    Tacrolimus minimization arm (low dose tacrolimus/tacrolimus reduced + everolimus + corticosteroids)
  • Drug: Tacrolimus
    Tacrolimus control arm (control dose tacrolimus + corticosteroids)
Study Arms / Comparison Groups
  • 1: Experimental
    Tacrolimus elimination arm (low dose tacrolimus until Month 4, then tacrolimus eliminated + everolimus + corticosteroids)
    Intervention: Drug: Everolimus
  • 3: Active Comparator
    Tacrolimus control arm (control dose tacrolimus + corticosteroids)
    Intervention: Drug: Tacrolimus
  • 2: Active Comparator
    Tacrolimus minimization arm (low dose tacrolimus/tacrolimus reduced + everolimus + corticosteroids)
    Intervention: Drug: Tacrolimus

Recruitment Information

Estimated Enrollment  ICMJE690
Completion Date 
Estimated Primary Completion DateJanuary 2010   (final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Ability and willingness to provide written informed consent and adhere to study regimen.
  • Recipients who are 18-70 years of age of a primary liver transplant from a deceased donor.
  • Recipients who have been initiated on an immunosuppressive regimen that contains corticosteroids and tacrolimus, 3-7 days post-transplantation.
  • Confirmed recipient HCV status at Screening (either by antibody or by PCR (Polymerase Chain Reaction).
  • Allograft is functioning at an acceptable level by the time of randomization as defined by protocol specific laboratory values.
  • Abbreviated MDRD eGFR ≥ 30 mL/min/1.73m2. Results obtained within 5 days prior to randomization are acceptable, however no sooner than Day 25 post-transplantation.
  • Verification of at least one tacrolimus trough level of ≥ 8 ng/mL in the week prior to randomization. Investigators should make adjustments in tacrolimus dosing to continue to target trough levels above 8 ng/mL prior to randomization.

Exclusion Criteria

  • Patients who are recipients of multiple solid organ or islet cell tissue transplants, or have previously received an organ or tissue transplant. Patients who have a combined liver-kidney transplant.
  • Recipients of a liver from a living donor, or of a split liver.
  • History of malignancy of any organ system within the past 5 years whether or not there is evidence of local recurrence or metastases, other than non-metastatic basal or squamous cell carcinoma of the skin, or HCC (Hepatocellular Carcinoma) (see next criteria).
  • Hepatocellular carcinoma that does not fulfill Milan criteria (1 nodule ≤5 cm, 2-3 nodules all <3 cm) at the time of transplantation as per explant histology of the recipient liver.
  • Any use of antibody induction therapy.
  • Patients with a known hypersensitivity to the drugs used on study or their class, or to any of the excipients
  • Patients who are recipients of ABO incompatible transplant grafts.
  • Recipients of organs from donors who test positive for Hepatitis B surface antigen or HIV are excluded.
  • Patients who have any surgical or medical condition, which in the opinion of the investigator, might significantly alter the absorption, distribution, metabolism and excretion of study drug.
  • Women of child-bearing potential (WOCBP)
  • Patients with any history of coagulopathy or medical condition requiring long-term anticoagulation which would preclude liver biopsy after transplantation. (Low dose aspirin treatment or interruption of chronic anticoagulant is allowed).

Other protocol-defined inclusion/exclusion criteria may apply.

GenderBoth
Ages18 Years to 70 Years
Accepts Healthy Volunteers 
Contacts  ICMJE
Contact: Novartis41613241111
Location Countries  ICMJEUnited States,   Argentina,   Australia,   Belgium,   Brazil,   Canada,   Colombia,   Czech Republic,   France,   Germany,   Hungary,   Ireland,   Israel,   Italy,   Netherlands,   Russian Federation,   Spain,   Sweden,   Switzerland,   United Kingdom

Administrative Information

NCT ID  ICMJENCT00622869
Responsible PartyExternal Affairs, Novartis Pharmaceticals
Study ID Numbers  ICMJECRAD001H2304
Study Sponsor  ICMJENovartis
Collaborators  ICMJE 
Investigators  ICMJE
Study Director:NovartisNovartis
Information Provided ByNovartis