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

NCT02453867 | Unknown Phase 4 DMC

• 2 other identifiers: REDUCE2014-002643-18
• Study Type: interventional
• Target: 400
• Locations: 0 countries
• Sites: N/A

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

Conditions

Immunosuppression After Renal Transplantation

Keywords

kidney transplantation; senior kidney transplant recipients; tacrolimus once daily; reduced immunosuppression; recipients >65 years; Senior

Outcome Measures

Primary Outcomes (1)

• Combined efficacy endpoint (BPAR, graft loss and death)

  BPAR (biopsy proven acute rejection)

  between randomization and month 12 posttransplant (month 9 of the study)

Secondary Outcomes (5)

• Number of severe infections

  between randomization and month 12 posttransplant

• Number of opportunistic infections

  between randomization and month 12 posttransplant

• Number of hospitalisations and days of hospitalisation

  between randomization and month 12 posttransplant

• Graft function by calculated glomarular filtration rate calculated by CKD-EPI

  between randomization and month 12 posttransplant

• Number of occurrences and types of donor specific antibodies (DSA)

  between randomization and month 12 posttransplant

Study Arms (2)

Standard immunosuppression

ACTIVE COMPARATOR

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

Drug: Tacrolimus; Drug: mycophenolate; Drug: Steroids

Reduced immunosuppression

EXPERIMENTAL

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

Other: Reduced immunosuppression; Drug: Tacrolimus; Drug: mycophenolate

Interventions

Reduced immunosuppression 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

Reduced immunosuppression

Tacrolimus DRUG

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

Also known as: Advagraf

Reduced immunosuppression; Standard immunosuppression

mycophenolate 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

Reduced immunosuppression; Standard immunosuppression

Steroids 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

Standard immunosuppression

Eligibility Criteria

• Age: 65 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• Males or females, aged ≥65 years and participating in the European SENIOR transplant registry
• Patients who received a renal allograft 3 - 3.5 months prior to randomization.
• Patient must have received primary or secondary renal allograft from a blood group compatible donor
• Standard criteria donors (SCD), expanded criteria donors (ECD), donors after cardiac death (DCD) and living donors (LD) are eligible
• Patients who are willing and able to participate in the study and from whom written informed consent has been obtained
• 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
• Stable graft function with serum creatinine ≤2.5 mg/dl.
• Patients with low to standard immunological risk, who had a PRA over 20% and no known donor specific antibodies (DSA) at transplantation

You may not qualify if:

• Patient with mental dysfunction or inability to comply with the study protocol
• Patients, who - according to the investigator - require for medical reasons (e.g. previous rejections) continuous triple therapy or a different tacrolimus exposure
• Multi-organ recipients (other solid organ (e.g. pancreas) or bone marrow)
• Blood group ABO-incompatible allografts
• 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
• History of antibody-mediated rejection (acute or chronic)
• Documented presence of donor specific antibodies (DSA) according to local lab results at baseline
• Panel reactive antibody (PRA) \>20% prior to transplantation, measured according to local standard
• Patients receiving or having received Sirolimus, Everolimus, Azathioprine, Belatacept or Cyclophosphamide within 3 months prior to enrolment
• Patients having received any other induction therapy than Basiliximab (e.g. depleting polyclonal antithymocyte antibodies (ATG), OKT3, Alemtuzumab)
• 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)
• History of alcohol or drug abuse with less than 6 months of sobriety
• Patient with a known hereditary immunodeficiency
• 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
• Patients with clinically symptomatic congestive heart failure or symptomatic coronary artery disease

Sponsors & Collaborators

• Klemens Budde: lead
• Charite University, Berlin, Germany: collaborator
• European Renal Association - European Dialysis and Transplant Association: collaborator
• European Kidney Transplant Association (EKITA): collaborator
• DESCARTES Working Group On Transplantation: collaborator

MeSH Terms

Interventions

Tacrolimus; Mycophenolic Acid; Steroids

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Klemens Budde, MD

  Charite Universitaetsmedizin Berlin

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lukas J Lehner, MD

CONTACT

004930450613559; lukas.lehner@charite.de

Klemens Budde, MD

CONTACT

004930450614086; klemens.budde@charite.de

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Prof. Dr.

Study Record Dates

• First Submitted: April 3, 2015
• First Posted: May 27, 2015
• Study Start: December 1, 2017
• Primary Completion: July 1, 2018
• Study Completion: July 1, 2019
• Last Updated: August 9, 2017

Record last verified: 2017-08

Data Sharing

• IPD Sharing: Will share