European Transplant Registry of Senior Renal Transplant Recipients on Advagraf

Study Overview
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Brief Summary
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SENIOR transplant Registry European transplant registry of senior renal transplant recipients (above the age of 65 years) receiving initial immunosuppression with tacrolimus once daily, mycophenolate and steroids to investigate long term outcomes on an observational basis.

Detailed Description
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The purpose of the registry is to establish data on the long-term outcome of elderly renal transplant recipients receiving an initial standard immunosuppression with tacrolimus once daily, mycophenolate and steroids The objectives of this registry are to investigate the long-term course of renal transplantation in the elderly European population (≥65 years) under immunosuppression with tacrolimus once daily, mycophenolate and steroids in order to better define risk factors for patient death and graft loss and predictors for favourable outcomes in this growing population. For this purpose, the SENIOR transplant registry will be implemented to collect data on graft loss, death, renal function, quality of life and biopsy proven acute rejections (BPAR), analyze common complications such as severe infections, opportunistic infections (CMV and/or BKV viremia), malignancies, cardiovascular events, and hospitalisations in a large population of European senior renal allograft recipients. In addition, type and severity of rejections (Banff-grade, steroid resistant rejections, antibody-mediated rejections, antibody-treated rejections, recurrent rejections), development of circulating donor specific antibodies (DSA), cardiovascular risk factors (such as diabetes, development of posttransplant diabetes (PTDM), hypertension), renal function (as estimated by CKD-EPI), and proteinuria will be longitudinally assessed in parallel to immunosuppressive doses and drug levels. The registry will focus on common side effects of immunosuppressive therapy (such as leucopenia, anemia), treatment patterns and reasons for treatment changes. Finally, a prospective analysis of quality of life including the burden of medication in elderly transplant recipients is planned. All recipients (≥65 years) of a kidney transplant who are willing to participate in the European SENIOR-Registry may enter the registry prior to transplantation if they are fulfilling all in- and none of the exclusion criteria and receive the intended initial immunosuppression consisting of tacrolimus once daily (Advagraf, initially adjusted to trough blood levels of ≥5ng/ml), mycophenolate (either ≥1.0g/day Mycophenolate Mofetil (MMF) or ≥720mg/d enteric-coated Mycophenolate Sodium (EC-MPS)) and Steroids. There will be 12 study visits during the 10 year period. Except for quality of life questionnaires there are no study specific procedures planned. Only data will be recorded which anyway will be recorded in clinical routine. The study population will consist of a representative group of approximately 1000 senior (≥65 years) kidney transplant patients, who receive a renal allograft and an initial standard triple immunosuppression (tacrolimus once daily (Advagraf), mycophenolate (either ≥1.0g/day Mycophenolate Mofetil (MMF) or ≥720mg/d enteric-coated Mycophenolate Sodium (EC-MPS)) and steroids. The patients will be recruited from approximately 42 transplant centers in Europe.

Official Title
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European Transplant Registry of Senior Renal Transplant Recipients Receiving Initial Immunosuppression With Tacrolimus Once Daily, Mycophenolate and Steroids

Conditions
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Graft Failure, Death, Acute Rejection of Renal Transplant, Infections, Bone Disease, Post Transplant Diabetes Mellitus, Quality of Life, HLA Antibody Production, Cardiovascular Risk Factors, Non-HLA Antibody Production

Intervention / Treatment
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* Drug: Tacrolimus once daily (Advagraf)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males or females, aged ≥65 years Patients who received a renal allograft Patients who are willing and able to participate in the study and from whom written informed consent has been obtained Patients on an intended standard triple therapy with tacrolimus once daily (Advagraf with trough level ≥5ng/ml) in combination with mycophenolate (either ≥1.0g/day MMF or ≥720mg/d EC-MPS) and Steroids (≥5mg prednisolone or equivalent) Patient must have received primary or secondary renal allograft from a blood group compatible donor (either deceased or living) Patients with low to standard immunological risk, who had a PRA 20% (PRA testing according to center's practice) or no known donor specific antibodies at transplantation Exclusion Criteria: Multi-organ recipients (solid organ or bone marrow) More than secondary renal allograft recipients Blood group A,B,O-incompatible allografts Documented presence of donor specific antibodies (DSA) Panel reactive antibody (PRA) >20% prior to transplantation (PRA testing according to center's practice) Patients having received any other induction therapy than Basiliximab or depleting polyclonal antithymocyte antibodies (ATG) (e.g. OKT3, Campath) Patients receiving Sirolimus, Everolimus, Azathioprine, Belatacept or Cyclophosphamide within 3 months prior to or at enrolment History of alcohol or drug abuse with less than 6 months of sobriety Patient with any condition that may affect absorption of immunosuppressives, (e.g. severe diarrhoea, gastrectomy, active peptic ulcer disease or clinically significant diabetic gastroenteropathy) or tacrolimus metabolism (e.g. liver cirrhosis) Patient with mental dysfunction or inability to cooperate within the study Patients who have been institutionalized by official or court order

Ages Eligible for Study
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Minimum Age: 65 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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Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Tacrolimus once daily (Advagraf)|Antibody induction by antithymocyte Globulin (ATG) or Basiliximab possible but not mandatory|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patient survival |  | From date of transplantation until the date of death from any cause, assessed up to 10 years | 
| Renal graft survival |  | From date of transplantation until the date of documented graft failure (need for permanent dialysis, explantation of the graft, retransplantation) or date of death from any cause, whichever came first, assessed up to 10 years | 
| Biopsy proven acute rejection (BPAR) | Type of rejection according to BANFF 2013 classification | Time of transplantation to date of first BPAR and consecutive BPARs, assessed up to 10 years | 
| Development of anti-HLA antibodies | type of antibodies (by HLA class and specificity), outcome after antibody production | Time of transplantation to date of first detection of any HLA antibodies, assesments are month 3 and year 1,3,5,7 and 10 in the central laboratory and all in all up to 10 years locally | 
| Renal graft function by estimated glomerular Filtration rate (eGFR) by CKD-EPI) calculation | Change of creatinine from baseline to the discrete observational visits, Calculation of eGFR (CKD-EPI) and eGFR slope | Assesment of renal graft function over time up to 10 years or graft failure or death, whichever comes first | 
| Development of non-HLA antibodies | type of antibodies, outcome after antibody production | Time of transplantation to date of first detection of any HLA antibodies, assesments are month 3 and year 1,3,5,7 and 10 in the central laboratory and all in all up to 10 years locally | 
| Development of donor specific antibodies (DSA) | type of antibodies (by HLA class and specificity), outcome after antibody production | Time of transplantation to date of first detection of any HLA antibodies, assesments are month 3 and year 1,3,5,7 and 10 in the central laboratory and all in all up to 10 years locally | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of kidney biopsies and suspected rejections | Incidence (number) of kidney biopsies and suspected rejections | from time of transplantation for up to 10 years | 
| Stroke | number and type of events | from time of transplantation up to 10 years | 
| Coronary revascularization procedure | number and type of events | from time of transplantation up to 10 years | 
| Carotid surgery | number and type of events | from time of transplantation up to 10 years | 
| Revascularisation procedures for symptomatic peripheral artery disease | number and type of events | from time of transplantation up to 10 years | 
| Symptomatic peripheral artery disease | number and type of Events, classification by Fontaine | from time of transplantation up to 10 years | 
| cardiac death | number and type of events | from time of transplantation to the date of the event for up to 10 years, whichever comes first | 
| non-fatal myocardial infarction | number and type of events | from time of transplantation to the date of the event for up to 10 years, whichever comes first | 
| Hospitalisations | Incidence of hospitalisations, reasons and length of hospitalisations | from time of transplantation up to 10 years | 
| Infections in general | Incidence of infections and type of infections | from time of transplantation up to 10 years | 
| Cytomegalovirus (CMV) disease | Incidence, defined by symptomatic CMV infection (including pulmonary and intestinal infections) | from time of transplantation up to 10 years | 
| CMV infection | Incidence, Defined by nucleic acid testing (NAT) in blood | from time of transplantation up to 10 years | 
| BKV (BK-Virus) infection | Incidence; Def: NAT testing in urine and blood or by biopsy staining | from time of transplantation up to 10 years | 
| Pneumocystis jiroveci pneumonia infection | Incidence | from time of transplantation up to 10 years | 
| Malignancies | Incidence, types of malignancies | from time of transplantation up to 10 years | 
| Post transplant diabetes mellitus | Incidence and time to development of posttransplant diabetes mellitus (PTDM) | from time of transplantation up to 10 years | 
| Immunosuppressants | Type of IS, Changes of IS | from time of transplantation up to 10 years | 
| Bone disease | number of fractures, measured height (meters) | from time of transplantation up to 10 years | 
| Quality of life measures | Quality of life by questionnaire (SF36, MTSODS) | from time of transplantation up to 10 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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elderly kidney transplant recipient, registry, tacrolimus once daily