European Transplant Registry of Senior Renal Transplant Recipients on Advagraf (SENIOR)

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Infections; Quality of Life; Death; Cardiovascular Risk Factors; Graft Failure; Bone Disease; Post Transplant Diabetes Mellitus; Acute Rejection of Renal Transplant; HLA Antibody Production; Non-HLA Antibody Production
• Intervention / Treatment: Drug: Tacrolimus once daily (Advagraf)

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.

• Study Type: Observational
• Enrollment (Anticipated): 1000

Contacts and Locations

• Study Contact: Name: Lukas J Lehner, MD; Phone Number: 613559 004930450; Email: lukas.lehner@charite.de
• Study Contact Backup: Name: Klemens Budde, MD; Phone Number: 614086 004930450; Email: klemens.budde@charite.de

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years and older (Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• 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.

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Klemens Budde
• Collaborators: Charite University, Berlin, Germany; Dr. med. univ. L. J. Lehner; ERA-EDTA; DESCARTES Working Group On Transplantation; European Kidney Transplant Association (EKITA)
• Investigators: Principal Investigator: Lukas J Lehner, MD, Charite University, Berlin, Germany

Study record dates

Study Major Dates

• Study Start: December 1, 2016
• Primary Completion (Anticipated): January 1, 2027
• Study Completion (Anticipated): January 1, 2028

Study Registration Dates

• First Submitted: September 19, 2015
• First Submitted That Met QC Criteria: September 22, 2015
• First Posted (Estimate): September 24, 2015

Study Record Updates

• Last Update Posted (Estimate): August 12, 2016
• Last Update Submitted That Met QC Criteria: August 11, 2016
• Last Verified: August 1, 2016

More Information

Terms related to this study

• Keywords: registry; elderly kidney transplant recipient; tacrolimus once daily
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Bone Diseases; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Immunosuppressive Agents; Immunologic Factors; Calcineurin Inhibitors; Tacrolimus
• Other Study ID Numbers: SENIOR

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: aggregated data are available through the Steering committee of DESCARTES and EKITA