Clinical trial NCT02558452: European Transplant Registry of Senior Renal Transplant Recipients on Advagraf
Official title: European Transplant Registry of Senior Renal Transplant Recipients Receiving Initial Immunosuppression With Tacrolimus Once Daily, Mycophenolate and Steroids
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: 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
Keywords: elderly kidney transplant recipient
registry
tacrolimus once daily
Lead sponsor: Charite University, Berlin, Germany
Sponsor class: OTHER
Collaborators: name: Dr. med. univ. L. J. Lehner
name: Charite University, Berlin, Germany
name: ERA-EDTA
name: DESCARTES Working Group On Transplantation
name: European Kidney Transplant Association (EKITA)
First posted: 2015-09-24
Enrollment: 1000
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: 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.

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Patient survival
timeFrame: From date of transplantation until the date of death from any cause, assessed up to 10 years
measure: Renal graft survival
timeFrame: 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
measure: Biopsy proven acute rejection (BPAR)
timeFrame: Time of transplantation to date of first BPAR and consecutive BPARs, assessed up to 10 years
measure: Development of anti-HLA antibodies
timeFrame: 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
measure: Renal graft function by estimated glomerular Filtration rate (eGFR) by CKD-EPI) calculation
timeFrame: Assesment of renal graft function over time up to 10 years or graft failure or death, whichever comes first
measure: Development of non-HLA antibodies
timeFrame: 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
measure: Development of donor specific antibodies (DSA)
timeFrame: 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 outcomes:
measure: Incidence of kidney biopsies and suspected rejections
timeFrame: from time of transplantation for up to 10 years
measure: Stroke
timeFrame: from time of transplantation up to 10 years
measure: Coronary revascularization procedure
timeFrame: from time of transplantation up to 10 years
measure: Carotid surgery
timeFrame: from time of transplantation up to 10 years
measure: Revascularisation procedures for symptomatic peripheral artery disease
timeFrame: from time of transplantation up to 10 years
measure: Symptomatic peripheral artery disease
timeFrame: from time of transplantation up to 10 years
measure: cardiac death
timeFrame: from time of transplantation to the date of the event for up to 10 years, whichever comes first
measure: non-fatal myocardial infarction
timeFrame: from time of transplantation to the date of the event for up to 10 years, whichever comes first
measure: Hospitalisations
timeFrame: from time of transplantation up to 10 years
measure: Infections in general
timeFrame: from time of transplantation up to 10 years
measure: Cytomegalovirus (CMV) disease
timeFrame: from time of transplantation up to 10 years
measure: CMV infection
timeFrame: from time of transplantation up to 10 years
measure: BKV (BK-Virus) infection
timeFrame: from time of transplantation up to 10 years
measure: Pneumocystis jiroveci pneumonia infection
timeFrame: from time of transplantation up to 10 years
measure: Malignancies
timeFrame: from time of transplantation up to 10 years
measure: Post transplant diabetes mellitus
timeFrame: from time of transplantation up to 10 years
measure: Immunosuppressants
timeFrame: from time of transplantation up to 10 years
measure: Bone disease
timeFrame: from time of transplantation up to 10 years
measure: Quality of life measures
timeFrame: from time of transplantation up to 10 years
Other outcomes:
Locations:
Study officials:
affiliation: Charite University, Berlin, Germany
name: Lukas J Lehner, MD
role: PRINCIPAL_INVESTIGATOR
References: