A Study Looking at Kidney Function in Kidney Transplant Recipients Who Are Taking Anti-rejection Medication Including Tacrolimus and With or Without Sirolimus.
Phase 4
Completed
- Conditions
- Kidney Transplantation
- Interventions
- Registration Number
- NCT01363752
- Lead Sponsor
- Astellas Pharma Inc
- Brief Summary
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
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 853
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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Advagraf + MMF + Steroids + Sirolimus Corticosteroids With sirolimus; MMF withdrawn on Day 28; Sirolimus introduced on Day 28 Advagraf + MMF + Steroids + Sirolimus Advagraf With sirolimus; MMF withdrawn on Day 28; Sirolimus introduced on Day 28 Advagraf + MMF + Steroids + Sirolimus Mycophenolate Mofetil With sirolimus; MMF withdrawn on Day 28; Sirolimus introduced on Day 28 Advagraf + MMF + Steroids Advagraf Without sirolimus Advagraf + MMF + Steroids Mycophenolate Mofetil Without sirolimus Advagraf + MMF + Steroids Corticosteroids Without sirolimus Advagraf + MMF + Steroids + Sirolimus Sirolimus With sirolimus; MMF withdrawn on Day 28; Sirolimus introduced on Day 28
- Primary Outcome Measures
Name Time Method Glomerular Filtration Rate (GFR) estimated by iohexol clearance at Week 52 post kidney transplantation up to 1 year
- Secondary Outcome Measures
Name Time Method 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 Subject survival up to 1 year Efficacy failure up to 1 year Composite endpoint defined as graft loss (re-transplantation, nephrectomy, death or dialysis ongoing at the study end) or subject withdrawal
New Onset Diabetes Mellitus (NODM) as per American Diabetic Association (ADA) criteria up to 1 year Incidence of Biopsy Confirmed Acute Rejection up to 1 year Time to Biopsy Confirmed Acute Rejection up to 1 year Graft survival up to 1 year Time to clinical acute rejection up to 1 year
Trial Locations
- Locations (58)
5042
🇦🇺New Lambton, Australia
5043
🇦🇺Perth, Australia
1141
🇦🇹Innsbruck, Austria
1142
🇦🇹Linz, Austria
1140
🇦🇹Vienna, Austria
3240
🇧🇾Minsk, Belarus
1241
🇧🇪Leuven, Belgium
1240
🇧🇪Liege 1, Belgium
Site 1441
🇨🇿Brno, Czechia
1440
🇨🇿Ostrava - Poruba, Czechia
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