European Transplant Registry of Senior Renal Transplant Recipients on Advagraf

Quality of Life Clinical Trial

— SENIOR  

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT02558452
• Other study ID #: SENIOR
• Status: Not yet recruiting
• Phase: N/A
• First received: September 19, 2015
• Last updated: August 11, 2016
• Start date: December 2016
• Est. completion date: January 2028

Study information

• Verified date: August 2016
• Source: Charite University, Berlin, Germany
• Contact: Lukas J Lehner, MD
• Phone: 004930450
• Email: lukas.lehner[@]charite.de
• Is FDA regulated: No
• Health authority: Germany: Ethics Commission
• Study type: Observational [Patient Registry]

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 1000
• Est. completion date: January 2028
• Est. primary completion date: January 2027
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 65 Years and older

Eligibility

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 Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

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

Intervention

Drug:
• Tacrolimus once daily (Advagraf)
Antibody induction by antithymocyte Globulin (ATG) or Basiliximab possible but not mandatory

Locations

Country	Name	City	State
n/a

Sponsors (6)

Lead Sponsor	Collaborator
Klemens Budde	DESCARTES working group on transplantation, Dr. med. univ. L. J. Lehner, EKITA (European Kidney Transplant Association), ERA-EDTA, Koordinierungszentrum Klinischer Studie der Charite Berlin (KKS Berlin)

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Patient survival		From date of transplantation until the date of death from any cause, assessed up to 10 years	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Secondary	Incidence of kidney biopsies and suspected rejections	Incidence (number) of kidney biopsies and suspected rejections	from time of transplantation for up to 10 years	No
Secondary	Stroke	number and type of events	from time of transplantation up to 10 years	No
Secondary	Coronary revascularization procedure	number and type of events	from time of transplantation up to 10 years	No
Secondary	Carotid surgery	number and type of events	from time of transplantation up to 10 years	No
Secondary	Revascularisation procedures for symptomatic peripheral artery disease	number and type of events	from time of transplantation up to 10 years	No
Secondary	Symptomatic peripheral artery disease	number and type of Events, classification by Fontaine	from time of transplantation up to 10 years	No
Secondary	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	No
Secondary	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	No
Secondary	Hospitalisations	Incidence of hospitalisations, reasons and length of hospitalisations	from time of transplantation up to 10 years	No
Secondary	Infections in general	Incidence of infections and type of infections	from time of transplantation up to 10 years	No
Secondary	Cytomegalovirus (CMV) disease	Incidence, defined by symptomatic CMV infection (including pulmonary and intestinal infections)	from time of transplantation up to 10 years	No
Secondary	CMV infection	Incidence, Defined by nucleic acid testing (NAT) in blood	from time of transplantation up to 10 years	No
Secondary	BKV (BK-Virus) infection	Incidence; Def: NAT testing in urine and blood or by biopsy staining	from time of transplantation up to 10 years	No
Secondary	Pneumocystis jiroveci pneumonia infection	Incidence	from time of transplantation up to 10 years	No
Secondary	Malignancies	Incidence, types of malignancies	from time of transplantation up to 10 years	No
Secondary	Post transplant diabetes mellitus	Incidence and time to development of posttransplant diabetes mellitus (PTDM)	from time of transplantation up to 10 years	No
Secondary	Immunosuppressants	Type of IS, Changes of IS	from time of transplantation up to 10 years	No
Secondary	Bone disease	number of fractures, measured height (meters)	from time of transplantation up to 10 years	No
Secondary	Quality of life measures	Quality of life by questionnaire (SF36, MTSODS)	from time of transplantation up to 10 years	No