Immunosuppression after kidney transplantion in elderly patients =65 years of age MedDRA version: 20.1 Level: PT Classification code 10062016 Term: Immunosuppression System Organ Class: 10021428 - Immune system disorders MedDRA version: 20.0 Level: LLT Classification code 10054990 Term: Immunodeficiency secondary to organ transplantation
Conditions
Interventions
Trade Name: Advagraf 0.5 mg prolonged-release hard capsules
Pharmaceutical Form: Prolonged-release capsule, hard
INN or Proposed INN: TACROLIMUS
CAS Num
Sponsors
Charité Universitätsmedizin Berlin
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Protocol chapter 4.1.1. Inclusion criteria 1. Males or females, aged =65 years and participating in the European SENIOR transplant registry 2. Patients who received a renal allograft 3 – 3.5 months prior to randomization. 3. Patient must have received primary or secondary renal allograft from a blood group compatible donor 4. Standard criteria donors (SCD), expanded criteria donors (ECD), donors after cardiac death (DCD) and living donors (LD) are eligible 5. Patients who are willing and able to participate in the study and from whom written informed consent has been obtained 6. Patients on continuous standard triple therapy with tacrolimus once daily (Advagraf®, trough level =5ng/ml) in combination with mycophenolate (either =1.0g/day MMF or =720mg/d EC-MPS) and steroids (=5mg prednisolone or equivalent) since transplantation 7. Stable graft function with serum creatinine =2.5 mg/dl. 8. Patients with low to standard immunological risk, who had a PRA below 20% or 20% and no known donor specific antibodies (DSA) at transplantation Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 400
Exclusion criteria
Exclusion criteria: Protocol chapter 4.1.2. Exclusion criteria 1. Patient with mental dysfunction or inability to comply with the study protocol 2. Patients, who - according to the investigator - require for medical reasons (e.g. previous rejections) continuous triple therapy or a different tacrolimus exposure 3. Multi-organ recipients (other solid organ (e.g. pancreas) or bone marrow) 4. Blood group ABO-incompatible allografts 5. Patients who suffered from severe T-cell mediated rejection (at least Banff II acute rejection), recurrent acute rejection (>1 episode), or steroid resistant rejection post-transplant 6. History of antibody-mediated rejection (acute or chronic) 7. History of rejection 2 months prior to inclusion 8. Documented presence of donor specific antibodies (DSA) according to local lab results at baseline 9. Panel reactive antibody (PRA) >20% prior to transplantation, measured according to local standard 10. Patients receiving or having received Sirolimus, Everolimus, Azathioprine, Belatacept or Cyclophosphamide within 3 months prior to enrolment 11. Patients having received any other induction therapy than Basiliximab (e.g. depleting polyclonal antithymocyte antibodies (ATG), OKT3, Alemtuzumab) 12. Patients with proteinuria >1.0 g/day (or >1.0 g/g creatinine) at screening or having experienced nephrotic syndrome due to recurrence of focal segmental glomerulosclerosis (FSGS) 13. History of alcohol or drug abuse with less than 6 months of sobriety 14. Patient with a known hereditary immunodeficiency 15. Patient with active malignancy posttransplant with the exception of local, non-invasive, fully excised, cutaneous basal cell carcinoma, cutaneous squamous cell carcinoma, or cervical carcinoma in situ 16. Patients with clinically symptomatic congestive heart failure or symptomatic coronary artery disease 17. Patients with documented (either by serology and/or nuclear acid testing (NAT) clinically active infections (e.g. with a known Hepatitis B, Hepatitis C, HIV, CMV or BK virus infection). Patients who do not have been screened in the previous 6 months, should be screened to confirm seronegativity before enrolment. 18. Participation in any other investigational clinical trial 3 months before participation in this study, except the SENIOR transplant registry 19. Patients with leukopenia ( 3x normal values 22. Any significant diseases or clinically significant findings, including psychiatric and behavioural problems, medical history and/or physical examination findings that would in the opinion of the investigator preclude the patient from participating in the study. 23. Patients who have been institutionalized by official or court order
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To establish efficacy and safety of a reduced immunosuppressive therapy with tacrolimus once daily for senior (>65 years of age) renal transplant recipients. Main objective: Non-inferiority of a reduced immunosuppressive therapy compared to standard therapy regarding a combined efficacy endpoint (BPAR, graft loss and death) between randomization (at month 3 post-transplant) and month 12 post-transplant ; Secondary Objective: Secondary objectives: - Incidence and time of graft loss - Incidence and time of death - Incidence and time of biopsy proven rejection - Evaluation infections: opportunistic (CMV, BKV), severe infections between study groups - Evaluation of kidney function by estimation of eGFR (CKD-EPI) between study Groups - Evaluation of hospitalisations - Evaluation of HLA antibody development and donor specific antibody (DSA) development - Evaluation of adverse and severe adverse events - Evaluation of post transplant Diabetes mellitus - Evaluation of laboratory result bundles (blood counts, etc.) - Evaluation of concomittant medication - Evaluation of quality of life measures - Assessment of Frailty ;Primary end point(s): Combined efficacy endpoint (BPAR, graft loss and death) between randomization (month 3 post-transpant) and month 12 posttransplant;Timepoint(s) of evaluation of this end point: Month 12 after transplantation. | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Month 12 after transplantation; Secondary end point(s): - Severe after randomization - Opportunistic infections after randomization, in particular - CMV Infection and CMV Viremia - BK Nephropathy and BK Viremia - Combined endpoint CMV and BK Viremia - Difference in renal function as estimated by the CKD-EPI [34], determined between treatment groups at month 6, 9 and 12 posttransplant. - Hospitalisations, hospitalisations for infections and hospitalisations for opportunistic infections (as confirmed by the investigator) after randomization - Time to efficacy failure (defined as any patient experiencing death, graft failure, BPAR) after randomization - Incidence and time of BPAR and/or graft loss, of graft loss and/or death, graft loss alone, death alone - Incidence and time to BPAR (Banff grade of at least IA) and Borderline rejection(s) after randomization according to BANFF classes 2013 - Incidence and time to clinically suspected and treated rejection episodes (treated acute rejection despite the absence of confirmatory evidence on a biopsy) and to steroid-resistant rejections, recurrent rejections, antibody-treated rejections and antibody-mediated acute rejection after randomization - Proportion of severity grades of the first episode of BPAR (Banff grade) occurring after randomization - Development of circulating anti-HLA-antibodies, non HLA-antibodies and/or de novo donor specific antibodies (DSA) - Change of renal function (according to CKD-EPI formula) from randomization to month 12 after transplantation. - Comparison of the GFR-slope between randomization and month 12 (according to CKD-EPI-formula) between groups - Incidence of patients with diffe | — |
Countries
Austria, Belgium, Czech Republic, Denmark, France, Germany, Italy, Netherlands, Norway, Poland, Spain, Sweden, United Kingdom
Contacts
Public ContactDivision of Nephrology
Charité Universitätsmedizin Berlin
Outcome results
None listed