Efficacy and Safety of a Reduced Immunosuppression vs. Standard Triple Therapy in Senior Renal Transplant Recipients

NCT ID: NCT02453867

Last Updated: 2017-08-09

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 400 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-12-31
• Study Completion Date: 2019-07-31

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

Conditions

Immunosuppression After Renal Transplantation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Standard immunosuppression

starting immunosuppression: tacrolimus (Advagraf) (target trough levels \>5 ng/ml), mycophenolate mofetil \>1g/d in MMF or \>720 mg/d in mycophenolic acid, steroids from month 1-3 dosing according to local practice; 200 pts are planned to carry on with standard immunosuppression (tacrolimus (Advagraf), Mycophenolate, steroids) as stated above according to international guidelines for kidney transplant recipients from month 3 posttransplant to month 12 posttransplant

Group Type: ACTIVE_COMPARATOR

Tacrolimus

Intervention Type: DRUG

Tacrolimus is used in both the acitve comparator arm and the interventional arm

mycophenolate

Intervention Type: DRUG

Mycophenolate is used in the acitve comparator arm for the whole study period; Mycophenolate is stopped at month 6 after Transplantation (month 3 of the study) in the experimental arm

Steroids

Intervention Type: DRUG

Steroids are used continually in the active comparator arm and are stopped at the beginning of the study (month 3 after Transplantation) as an Intervention in the experimental arm

Reduced immunosuppression

The Intervention is stopping medication:

200 pts are planned to receive a reduced immunosuppression after month 3: carry on with tacrolimus (Advagraf; trough levels >5 ng/ml) steroids stop at month 3 mycophenolate stop at month 6

Group Type: EXPERIMENTAL

Reduced immunosuppression

Intervention Type: OTHER

Stop steroids at month 3 Stop mycophenolate at month 6 continue tacrolimus once daily (Advagraf, trough levels \> 5ng/ml) Stop mycophenolate at month 6

Tacrolimus

Intervention Type: DRUG

Tacrolimus is used in both the acitve comparator arm and the interventional arm

mycophenolate

Intervention Type: DRUG

Mycophenolate is used in the acitve comparator arm for the whole study period; Mycophenolate is stopped at month 6 after Transplantation (month 3 of the study) in the experimental arm

Interventions

Reduced immunosuppression

Stop steroids at month 3 Stop mycophenolate at month 6 continue tacrolimus once daily (Advagraf, trough levels \> 5ng/ml) Stop mycophenolate at month 6

Intervention Type: OTHER

Tacrolimus

Tacrolimus is used in both the acitve comparator arm and the interventional arm

Intervention Type: DRUG

mycophenolate

Mycophenolate is used in the acitve comparator arm for the whole study period; Mycophenolate is stopped at month 6 after Transplantation (month 3 of the study) in the experimental arm

Intervention Type: DRUG

Steroids

Steroids are used continually in the active comparator arm and are stopped at the beginning of the study (month 3 after Transplantation) as an Intervention in the experimental arm

Intervention Type: DRUG

Other Intervention Names

Advagraf

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

• Minimum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Charite University, Berlin, Germany

OTHER

Sponsor Role: collaborator

European Renal Association - European Dialysis and Transplant Association

OTHER

Sponsor Role: collaborator

European Kidney Transplant Association (EKITA)

OTHER

Sponsor Role: collaborator

DESCARTES Working Group On Transplantation

OTHER

Sponsor Role: collaborator

Klemens Budde

OTHER

Sponsor Role: lead

Responsible Party

Klemens Budde

Prof. Dr.

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Klemens Budde, MD

Role: PRINCIPAL_INVESTIGATOR

Charite Universitaetsmedizin Berlin

Central Contacts

Lukas J Lehner, MD

Role: CONTACT

lukas.lehner@charite.de

004930450613559

Klemens Budde, MD

Role: CONTACT

klemens.budde@charite.de

004930450614086

Other Identifiers

2014-002643-18

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

REDUCE

Identifier Type: -

Identifier Source: org_study_id