Immunosuppression After Renal TransplantationPhase 4REDUCENCT02453867
Efficacy and Safety of a Reduced Immunosuppression vs. Standard Triple Therapy in Senior Renal Transplant Recipients
A Phase 4 study testing Reduced immunosuppression, Tacrolimus and mycophenolate in people with Immunosuppression After Renal Transplantation, run by Klemens Budde.
Trial 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 Read more about this study
- Who is it for?
- Ages 65 years and older
- Conditions the study is for
- Immunosuppression After Renal Transplantation
- What is being tested?
- Reduced immunosuppression, Tacrolimus and mycophenolate
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 400 participants
- Where
- No sites listed yet
- Study dates
- Dec 2017to Jul 2019
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 65 years and older
- All sexes
- No healthy volunteers
- Older adult
Who may be able to join
- 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
Who cannot join
- 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)
Show all 23Show fewer
- History of rejection 2 months prior to inclusion
- 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
- 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)
- Participation in any other investigational clinical trial 3 months before participation in this study, except the SENIOR transplant registry
- Patients with leukopenia (<2500 cells/nl) or neutropenia (<1500 cells/nl)
- Patients with thrombocytopenia (<100 cells/nl)
- Patients with liver transaminases or bilirubin values > 3x normal values
- 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.
- Patients who have been institutionalized by official or court order
Trial locations and contacts
No sites are listed yet.
About this study
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 purpose To establish efficacy and safety of a reduced immunosuppressive therapy with tacrolimus once daily for senior (>65 years of age) renal transplant recipients
Read the 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
- Being tested
- Reduced immunosuppression, Tacrolimus, mycophenolate, Steroids
- Keywords
- kidney transplantation, senior kidney transplant recipients, tacrolimus once daily, reduced immunosuppression, recipients >65 years, Senior
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Reduced immunosuppressionOther
Stop steroids at month 3 Stop mycophenolate at month 6 continue tacrolimus once daily (Advagraf, trough levels > 5ng/ml) Stop mycophenolate at month 6
TacrolimusDrug
Also called Advagraf
Tacrolimus is used in both the acitve comparator arm and the interventional arm
mycophenolateDrug
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
SteroidsDrug
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
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: Other: Reduced immunosuppression; Drug: Tacrolimus; Drug: mycophenolate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Combined efficacy endpoint (BPAR, graft loss and death)
BPAR (biopsy proven acute rejection)
Measured: between randomization and month 12 posttransplant (month 9 of the study)
Secondary outcomes (5)
Number of severe infections
Numbers, type of infections will be registered
Measured: between randomization and month 12 posttransplant
Number of opportunistic infections
CMV infections, BKV infections; numbers, type of infection will be registered
Measured: between randomization and month 12 posttransplant
Number of hospitalisations and days of hospitalisation
number of episodes, days in hospital
Measured: between randomization and month 12 posttransplant
Graft function by calculated glomarular filtration rate calculated by CKD-EPI
Comparison of estimated glomerular filtration rate calculated by CKD-EPI formula
Measured: between randomization and month 12 posttransplant
Number of occurrences and types of donor specific antibodies (DSA)
surveillance of detection of new donor specific antibodies by Luminex assay
Measured: between randomization and month 12 posttransplant
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 May 2015 (estimated)
- Study startDec 2017 (estimated)
- Primary completionJul 2018 (estimated)
- Study completionJul 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Immunosuppression After Renal TransplantationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 400 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Klemens Budde
- Sponsor type
- University, hospital or other
- Collaborators
- Charite University, Berlin, Germany, European Renal Association - European Dialysis and Transplant Association, European Kidney Transplant Association (EKITA), DESCARTES Working Group On Transplantation
- Responsible party
- Sponsor-investigator, Klemens Budde, Charite University, Berlin, Germany
- Investigators
- Klemens Budde, MD, Principal investigator, Charite Universitaetsmedizin Berlin
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02453867
- Sponsor's protocol ID
- REDUCE
- Other IDs
- 2014-002643-18, 2014
- Acronym
- REDUCE
- Status last verified
- Aug 2017
- First submitted
- 3 Apr 2015
- Last updated
- 9 Aug 2017
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: aggregated data are available through the Steering committee of DESCARTES and EKITA
Study at a glance
From the registry record, last updated by the sponsor on 9 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02453867
- Acronym / sponsor ID
- REDUCE / REDUCE
- Keywords
- kidney transplantation, senior kidney transplant recipients, tacrolimus once daily, reduced immunosuppression, recipients >65 years, Senior
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 400 participants (estimated)
- Lead sponsor
- Klemens BuddeUniversity, hospital or other
- Collaborators
- Charite University, Berlin, Germany, European Renal Association - European Dialysis and Transplant Association, European Kidney Transplant Association (EKITA), DESCARTES Working Group On Transplantation
- Study start
- Dec 2017 (estimated)
- Primary completion
- Jul 2018 (estimated)
- Study completion
- Jul 2019 (estimated)
- First posted
- 27 May 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Standard immunosuppression | Active comparator | Drug: Tacrolimus, Drug: mycophenolate, Drug: Steroidsstarting 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 |
| Reduced immunosuppression | Experimental | Other: Reduced immunosuppression, Drug: Tacrolimus, Drug: mycophenolateThe 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 |
Who may qualify
- Ages
- 65 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Older adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (23 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Reduced immunosuppressionStop steroids at month 3 Stop mycophenolate at month 6 continue tacrolimus once daily (Advagraf, trough levels > 5ng/ml) Stop mycophenolate at month 6 | Other | Reduced immunosuppression |
| TacrolimusAlso: AdvagrafTacrolimus is used in both the acitve comparator arm and the interventional arm | Drug | Reduced immunosuppression, Standard immunosuppression |
| mycophenolateMycophenolate 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 | Drug | Reduced immunosuppression, Standard immunosuppression |
| SteroidsSteroids 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 | Drug | Standard immunosuppression |
Primary outcome
Combined efficacy endpoint (BPAR, graft loss and death)
Time frame: between randomization and month 12 posttransplant (month 9 of the study)
BPAR (biopsy proven acute rejection)
5 secondary outcomes
Number of severe infections
Time frame: between randomization and month 12 posttransplant
Number of opportunistic infections
Time frame: between randomization and month 12 posttransplant
Number of hospitalisations and days of hospitalisation
Time frame: between randomization and month 12 posttransplant
Graft function by calculated glomarular filtration rate calculated by CKD-EPI
Time frame: between randomization and month 12 posttransplant
Number of occurrences and types of donor specific antibodies (DSA)
Time frame: between randomization and month 12 posttransplant
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Aug 2017.
- Individual participant dataSharing planned: Yes. aggregated data are available through the Steering committee of DESCARTES and EKITA
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Klemens Budde, MD principal investigator
Charite Universitaetsmedizin Berlin
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Reduced immunosuppression, Tacrolimus and mycophenolate in people with Immunosuppression After Renal Transplantation, run by Klemens Budde.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 9 Aug 2017. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Lukas J Lehner, MD (004930450613559, lukas.lehner@charite.de), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Combined efficacy endpoint (BPAR, graft loss and death) (time frame: between randomization and month 12 posttransplant (month 9 of the study)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Aug 2017.