Clinical trial NCT02453867: Efficacy and Safety of a Reduced Immunosuppression vs. Standard Triple Therapy in Senior Renal Transplant Recipients
Official title: Multicenter, Prospective, Randomized Study Investigating the Efficacy and Safety of a Reduced Immunosuppressive Therapy With Tacrolimus Once Daily in Comparison to Standard Triple Immunosuppression in Senior Renal Transplant Recipients
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Immunosuppression After Renal Transplantation
Keywords: kidney transplantation
senior kidney transplant recipients
tacrolimus once daily
reduced immunosuppression
recipients >65 years
Senior
Lead sponsor: Charite University, Berlin, Germany
Sponsor class: OTHER
Collaborators: name: Charite University, Berlin, Germany
name: European Renal Association - European Dialysis and Transplant Association
name: European Kidney Transplant Association (EKITA)
name: DESCARTES Working Group On Transplantation
First posted: 2015-05-27
Enrollment: 400
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Study purpose To establish efficacy and safety of a reduced immunosuppressive therapy with tacrolimus once daily for senior (\>65 years of age) renal transplant recipients

Detailed description: Study outline Stable senior transplant recipients (\>65 years of age) participating in the European SENIOR transplant registry may enter the trial at month 3 post-transplant, if they fulfil all of the in- and none of the exclusion criteria. At this time patients will be randomized 1:1 either to continue

Reference therapy:

Tacrolimus once daily (Advagraf®) Mycophenolate (either MMF ≥1g/d or EC-MPS ≥720g/d) Steroids (≥5mg prednisolone or equivalent) or to Investigational therapy: Tacrolimus once daily (Advagraf®) Steroid stop at month 3 (tapering within 2 weeks) Mycophenolate stop at month 6

Eligibility criteria: 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 over 20% and no known donor specific antibodies (DSA) at transplantation

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 (over 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)
18. Participation in any other investigational clinical trial 3 months before participation in this study, except the SENIOR transplant registry
19. Patients with leukopenia (\<2500 cells/nl) or neutropenia (\<1500 cells/nl)
20. Patients with thrombocytopenia (\<100 cells/nl)
21. Patients with liver transaminases or bilirubin values \> 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

Primary outcomes:
measure: Combined efficacy endpoint (BPAR, graft loss and death)
timeFrame: between randomization and month 12 posttransplant (month 9 of the study)
Secondary outcomes:
measure: Number of severe infections
timeFrame: between randomization and month 12 posttransplant
measure: Number of opportunistic infections
timeFrame: between randomization and month 12 posttransplant
measure: Number of hospitalisations and days of hospitalisation
timeFrame: between randomization and month 12 posttransplant
measure: Graft function by calculated glomarular filtration rate calculated by CKD-EPI
timeFrame: between randomization and month 12 posttransplant
measure: Number of occurrences and types of donor specific antibodies (DSA)
timeFrame: between randomization and month 12 posttransplant
Other outcomes:
Locations:
Study officials:
affiliation: Charite Universitaetsmedizin Berlin
name: Klemens Budde, MD
role: PRINCIPAL_INVESTIGATOR
References: