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Efficacy and Safety of Concentration-Controlled Everolimus to Eliminate or to Reduce Tacrolimus Compared to Tacrolimus in de Novo Liver Transplant Recipients (RAD)
This study is currently recruiting participants.
Verified by Novartis, September 2008
Sponsored by: Novartis
Information provided by: Novartis
ClinicalTrials.gov Identifier: NCT00622869
  Purpose

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.


Condition Intervention Phase
Liver Transplantation
Drug: Everolimus
Drug: Tacrolimus
Phase III

MedlinePlus related topics: Liver Transplantation
Drug Information available for: Tacrolimus Everolimus Corticosteroids Tacrolimus anhydrous
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study
Official Title: A 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

Further study details as provided by Novartis:

Primary Outcome Measures:
  • 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.

Secondary Outcome Measures:
  • 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.

Estimated Enrollment: 690
Study Start Date: January 2008
Arms Assigned Interventions
1: Experimental
Tacrolimus elimination arm (low dose tacrolimus until Month 4, then tacrolimus eliminated + everolimus + corticosteroids)
Drug: Everolimus
Tacrolimus elimination arm (low dose tacrolimus until Month 4, then tacrolimus eliminated + everolimus + corticosteroids)
3: Active Comparator
Tacrolimus control arm (control dose tacrolimus + corticosteroids)
Drug: Tacrolimus
Tacrolimus control arm (control dose tacrolimus + corticosteroids)
2: Active Comparator
Tacrolimus minimization arm (low dose tacrolimus/tacrolimus reduced + everolimus + corticosteroids)
Drug: Tacrolimus
Tacrolimus minimization arm (low dose tacrolimus/tacrolimus reduced + everolimus + corticosteroids)

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Criteria

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.

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00622869

Contacts
Contact: Novartis 41613241111

  Show 94 Study Locations
Sponsors and Collaborators
Novartis
Investigators
Study Director: Novartis Novartis
  More Information

Responsible Party: Novartis ( Novartis )
Study ID Numbers: CRAD001H2304
Study First Received: February 13, 2008
Last Updated: September 8, 2008
ClinicalTrials.gov Identifier: NCT00622869  
Health Authority: Italy: The Italian Medicines Agency;   United States: Food and Drug Administration

Keywords provided by Novartis:
Liver transplantation
everolimus
calcineurin inhibitors
tacrolimus
renal function
MDRD formula
progression of fibrosis

Study placed in the following topic categories:
Everolimus
Fibrosis
Disease Progression
Tacrolimus

Additional relevant MeSH terms:
Immunologic Factors
Physiological Effects of Drugs
Immunosuppressive Agents
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 16, 2009