Efficacy and Safety of Concentration-controlled Everolimus to Eliminate or to Reduce Tacrolimus Compared to Tacrolimus in de Novo Liver Transplant Recipients (RAD)
Tracking InformationStart Date ICMJE | January 2008 |
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Estimated Primary Completion Date | January 2010 (final data collection date for primary outcome measure) |
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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. |
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Original Primary Outcome Measures ICMJE | Same as current |
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Change History | Complete list of historical versions of study NCT00622869 on ClinicalTrials.gov Archive Site |
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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. |
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Original Secondary Outcome Measures ICMJE | Same as current |
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Descriptive InformationBrief Title ICMJE | Efficacy and Safety of Concentration-controlled Everolimus to Eliminate or to Reduce Tacrolimus Compared to Tacrolimus in de Novo Liver Transplant Recipients |
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Official Title ICMJE | 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 |
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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. |
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Detailed Description | |
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Study Phase | Phase III |
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Study Type ICMJE | Interventional |
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Study Design ICMJE | Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study |
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Condition ICMJE | Liver Transplantation |
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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)
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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
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Recruitment InformationEstimated Enrollment ICMJE | 690 |
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Completion Date | |
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Estimated Primary Completion Date | January 2010 (final data collection date for primary outcome measure) |
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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. |
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Gender | Both |
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Ages | 18 Years to 70 Years |
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Accepts Healthy Volunteers | |
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Contacts ICMJE | Contact: Novartis | 41613241111 | | |
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Location Countries ICMJE | United States, Argentina, Australia, Belgium, Brazil, Canada, Colombia, Czech Republic, France, Germany, Hungary, Ireland, Israel, Italy, Netherlands, Russian Federation, Spain, Sweden, Switzerland, United Kingdom |
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Administrative InformationNCT ID ICMJE | NCT00622869 |
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Responsible Party | External Affairs, Novartis Pharmaceticals |
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Study ID Numbers ICMJE | CRAD001H2304 |
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Study Sponsor ICMJE | Novartis |
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Collaborators ICMJE | |
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Investigators ICMJE | Study Director: | Novartis | Novartis | |
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Information Provided By | Novartis |
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