A Study Looking at Kidney Function in Kidney Transplant Recipients Who Are Taking Anti-rejection Medication Including Tacrolimus and With or Without Sirolimus.

Study Overview
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Brief Summary
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The purpose of this study is to compare the effect of two anti-rejection therapy regimens on kidney function in kidney transplant recipients.

Detailed Description
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This study will evaluate the potential to reduce nephrotoxic calcineurin inhibitors (CNI) therapy by lowering tacrolimus exposure from Advagraf® in combination with the non-nephrotoxic immunosuppressant sirolimus to avoid the risk of acute graft rejection, compared with an Advagraf® and Mycophenolate Mofetil (MMF) immunosuppressive regimen.

Official Title
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A Multicenter, Two Arm, Randomized, Open Label Clinical Study Investigating Renal Function in an Advagraf® Based Immunosuppressive Regimen With or Without Sirolimus in Kidney Transplant Patients

Conditions
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Kidney Transplantation

Intervention / Treatment
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* Drug: Advagraf
* Drug: Mycophenolate Mofetil
* Drug: Sirolimus
* Drug: Corticosteroids


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: End stage kidney disease and a suitable candidate for primary renal transplantation or re-transplantation (unless the graft was lost from rejection within 6 months) Receiving a kidney transplant from a deceased or living (non Human Leukocyte Antigen [HLA] identical) donor with compatible ABO blood type Female subject of childbearing potential has a negative serum or urine pregnancy test at enrollment Female and male subjects agree to maintain highly effective birth control during the study and for 90 days after discontinuation of dosing with study drugs. A highly effective method of birth control is defined as those which result in a low failure rate (CPMP/ ICH/ 286/ 95 modified) of less than 1% per year when used consistently and correctly such as implants, injectables, combined oral contraceptives, some Intrauterine Devises (IUDs), sexual abstinence or vasectomized partner Exclusion Criteria: Receiving or having previously received an organ transplant other than a kidney Cold ischemia time of the donor kidney > 30 hours Panel Reactive Antibody (PRA) >20% Receiving a graft from a non-heart-beating donor other than of Maastricht category 3 (withdrawal of support awaiting cardiac arrest) Significant liver disease, defined as having continuously elevated SGPT/ ALT and/ or SGOT/ AST and/ or total bilirubin levels ≥ 2 times the upper value of the normal range of the investigational site or is receiving a graft from a hepatitis C or B positive donor Requiring initial sequential or parallel therapy with immunosuppressive antibody preparation(s) Requiring ongoing dosing with a systemic immunosuppressive drug prior to transplantation (other than minimal levels of immunosuppression following failure of previous transplantation without nephrectomy) Significant, uncontrolled concomitant infections and/ or severe diarrhea, vomiting, active upper gastro-intestinal tract malabsorption or active peptic ulcer Pregnant woman or breast-feeding mother Subject or donor known to be HIV positive Known allergy or intolerance to tacrolimus, macrolide antibiotics, corticosteroids, sirolimus, MMF or any of the product excipients or iodine Evidence of malignant disease within the last 5 years, not including non-malignant skin cancers Currently participating in another clinical trial, and/ or has taken an investigational drug within 28 days prior to enrollment Unlikely to comply with the visits scheduled in the protocol

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Advagraf + MMF + Steroids<br>Without sirolimus | Drug: Advagraf<br>* oral<br>* Other names: Prolonged release tacrolimus;Drug: Mycophenolate Mofetil<br>* oral<br>* Other names: CellCept;Drug: Corticosteroids<br>* i.v. and oral<br>|
| Experimental: Advagraf + MMF + Steroids + Sirolimus<br>With sirolimus; MMF withdrawn on Day 28; Sirolimus introduced on Day 28 | Drug: Advagraf<br>* oral<br>* Other names: Prolonged release tacrolimus;Drug: Mycophenolate Mofetil<br>* oral<br>* Other names: CellCept;Drug: Sirolimus<br>* oral<br>* Other names: Rapamune;Drug: Corticosteroids<br>* i.v. and oral<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glomerular Filtration Rate (GFR) estimated by iohexol clearance at Week 52 post kidney transplantation |  | up to 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy failure | Composite endpoint defined as graft loss (re-transplantation, nephrectomy, death or dialysis ongoing at the study end) or subject withdrawal | up to 1 year | 
| GFR at Week 52 post kidney transplantation by Modification Diet in Renal Disease (MDRD) formula |  | up to 1 year | 
| GFR at Week 52 post kidney transplantation by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula |  | up to 1 year | 
| Calculated creatinine clearance at Week 52 post kidney transplantation by Cockcroft and Gault formula |  | up to 1 year | 
| Incidence of clinical acute rejection |  | up to 1 year | 
| Time to clinical acute rejection |  | up to 1 year | 
| Incidence of Biopsy Confirmed Acute Rejection |  | up to 1 year | 
| Time to Biopsy Confirmed Acute Rejection |  | up to 1 year | 
| Subject survival |  | up to 1 year | 
| Graft survival |  | up to 1 year | 
| New Onset Diabetes Mellitus (NODM) as per American Diabetic Association (ADA) criteria |  | up to 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Kidney, Kidney Failure, Acute, Astagraf XL, Immunosuppression, Advagraf, Tacrolimus, Transplant