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Renal Transplant RecipientsPhase 4OPTIMIZENCT03797196

RCT Comparing Immunosuppressive Regimens in Elderly Renal Transplant Recipients

A Phase 4 study testing low dose tacrolimus in combination with everolimus and standard dose tacrolimus with mycophenolate mofetil in people with Renal Transplant Recipients and Elderly Patients, run by University Medical Center Groningen at 7 sites in 2 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

Open label, randomized, multicenter, intervention trial comparing standard immunosuppression with tacrolimus and mycophenolate mofetil with a low exposure tacrolimus regimen in combination with everolimus. Read more about this study

Who is it for?
Ages 65 to 99 years
What is being tested?
low dose tacrolimus in combination with everolimus and standard dose tacrolimus with mycophenolate mofetil
Could I receive a placebo?
No, everyone receives an active treatment
How many people
374 participants
Where
7 sitesin 2 countries
Study dates
29 Jul 2019to Dec 2026
Phase
Phase 4
Are there results?
Not yet: the study is under way

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 to 99 years
  • All sexes
  • No healthy volunteers
  • Older adult

Who may be able to join

  • Written informed consent must be obtained before any assessment is performed
  • Male or female subject ≥65 years old
  • Subject randomized within 24 hours of completion of transplant surgery
  • Stratum A: Recipient of a primary (or secondary, if first graft is not lost due to immunological reasons) renal transplant from a deceased donor aged 65 years or older
  • Stratum B: Recipient of a primary (or secondary, if first graft is not lost due to immunological reasons) renal transplant from a deceased donor aged below 65 years or a living donor of any age
  • Exclusion Criteria: Exclusion criteria for both stratum A and B
Show all 19Show fewer
  • Subject is a multi-organ transplant recipient
  • Recipient of bloodgroup ABO incompatible allograft or CDC cross-match positive transplant
  • Subject at high immunological risk for rejection as determined by local practice for assessment of anti-donor reactivity
  • Recipient of a kidney with a cold ischaemia time (CIT) >24 hr
  • Recipients of a kidney from an HLA-identical related living donor
  • Known intolerability for one or more of the study drugs
  • Subject who is HIV positive
  • HBsAg and/or a HCV positive subject with evidence of elevated liver function tests (ALT/AST levels ≥2.5 times ULN). Viral serology results obtained within 6 months prior to randomization are acceptable
  • Recipient of a kidney from a donor who tests positive for human immunodeficiency virus, (HIV), hepatitis B surface antigen (HBsAg) or anti-hepatitis C virus (HCV)
  • Subject with severe systemic infections, current or within the two weeks prior to randomization
  • Subject with severe restrictive or obstructive pulmonary disorders
  • Subject with severe hypercholesterolemia or hypertriglyceridemia that cannot be controlled
  • Subject with white blood cell (WBC) count ≤ 2,000/mm3 or with platelet count ≤ 50,000/mm3

Who cannot join

None listed.

Trial locations and contacts

7 sites in 2 countries.

7 sites in 2 countries

Netherlands6 sites

  • Amsterdam UMC

    Amsterdam

  • UMCG

    Groningen

  • LUMC

    Leiden

  • Radboud University Hospital

    Nijmegen

  • Erasmus MC

    Rotterdam

  • UMCU

    Utrecht

Other trials in Netherlands

Belgium1 site

  • Leuven University Hospital

    Leuven

Other trials in Belgium

About this study

Official title: Open Label Multicenter Randomized Trial Comparing Standard Immunosuppression With Tacrolimus and Mycophenolate Mofetil With a Low Exposure Tacrolimus Regimen in Combination With Everolimus in de Novo Renal Transplantation in Elderly Patient

Open label, randomized, multicenter, intervention trial comparing standard immunosuppression with tacrolimus and mycophenolate mofetil with a low exposure tacrolimus regimen in combination with everolimus.

The primary objective is to test the hypothesis that an age-adapted immunosuppressive regimen targeted at reduced immunosuppression with low calcineurin inhibitor (tacrolimus) exposure in combination with everolimus will result in improved outcome in elderly recipients of A: Kidneys from older deceased donors (>64 years) and B: Kidneys from living donors (all ages) and younger deceased donors (<65 years).

Read the detailed description

In this study two immunosuppressive regimes will be tested; In both groups basiliximab induction will be applied. Additionally, the standard therapy consisting of prednisolone, mycophenolic acid and tacrolimus once-daily (Envarsus®), or the comparator in which mycophenolic acid will be replaced by everolimus combined with strongly reduced levels of tacrolimus once-daily (Envarsus®). When not tolerated,tacrolimus may be replaced by ciclosporin. The hypothesis is that reduced calcineurin inhibitor (CNI) exposure in combination with everolimus will lead to improved allograft function, a reduced incidence of complications and improved quality of life.

This study will consist of two strata: Stratum A: Elderly recipients (≥65 years) of kidneys from elderly deceased donors (≥65 years) within the Eurotransplant Senior Program. Stratum B: Elderly recipients (≥65 years) of kidneys from living donors (all ages) or deceased donors (<65 years). The primary endpoint will be "successful transplantation" which is defined as survival with a functioning allograft with a minimum estimated GFR of 30 ml/min per 1.73 m2 in stratum A and 45 ml/min per 1.73 m2 in stratum B, after 2 years.

The study will be performed by the Dutch transplant centers and the Dutch Kidney Patient Organization (NVN) will participate.

Being tested
low dose tacrolimus in combination with everolimus, standard dose tacrolimus with mycophenolate mofetil

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • low dose tacrolimus in combination with everolimusDrug

    a low exposure Tacrolimus once-daily (Envarsus®) regimen in combination with Everolimus will be evaluated in elderly transplant recipients

  • standard dose tacrolimus with mycophenolate mofetilDrug

    A standard Tacrolimus once-daily (Envarsus) regimen in combination with Everolimus will be evaluated in elderly transplant recipients

Study groups in NCT03797196
Study groupRoleWhat they receive
group 1Active comparatorstandard tacrolimus with mycophenolate mofetil
Receives: Drug: standard dose tacrolimus with mycophenolate mofetil
group 2Experimentallow dose tacrolimus with everolimus
Receives: Drug: low dose tacrolimus in combination with everolimus

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. successful transplantation

    The overall primary study endpoint "successful transplantation" as defined for the individual strata and analyzed for the whole study population.

    Stratum A: Primary endpoint: successful transplantation at two years after transplantation defined as: absence of graft or patient loss in the presence of an eGFR above 30 ml/min/1.73m2.

    Stratum B: Primary endpoint: successful transplantation at two years after transplantation defined as absence of graft or patient loss in the presence of an eGFR above 45 ml/min/1.73m2

    Measured: 24 months

Secondary outcomes (20)

  1. death

    patient survival

    Measured: 24 months

  2. graft loss

    graft survival

    Measured: 24 months

  3. acute rejection

    treated biopsy-proven rejection (tBPAR)

    Measured: 24 months

  4. eGFR

    estimated Glomerular Filtration Rate below 30 and 45 ml/min/1.73m2

    Measured: 12 and 24 months

  5. type of rejection treatment

    type of rejection treatment will be scored by questionnaire to the treating nephrologist

    Measured: 24 months

  6. The evolution of renal function (eGFR) and creatinine clearance over time by slope analysis

    The evolution of renal function (eGFR) and creatinine clearance over time by slope analysis

    Measured: 24 months

  7. The incidence of adverse events, serious adverse events and adverse reactions

    The incidence of adverse events, serious adverse events and adverse reactions

    Measured: 24 months

  8. The incidence of clinically relevant infections, post transplantation diabetes mellitus, malignancies and cardiovascular events

    The incidence of clinically relevant infections, post transplantation diabetes, malignancies and cardiovascular events

    Measured: 24 months

  9. Presence of frailty after transplantation and change in frailty from baseline frailty from baseline

    frailty is measured by clinical frailty score, hand grip strength and fried frailty index

    Measured: 12 and 24 months

  10. Physical functioning and changes over time

    Short Physical Performance Battery

    Measured: 24 months

  11. Cognitive functioning and changes over time

    Montreal Cognitive Assessment

    Measured: 24 months

  12. Presence of T-cell immunosenescence at 12 and 24 months and changes from baseline

    T cell differentiation, exhaustion and telomere length will be assessed by flowcytometry

    Measured: 24 months

  13. HRQoL at 0, 12 and 24 months and changes from baseline

    Questionnaire: EQ-5D and SF-12

    Measured: 24 months

  14. Development of donor-specific anti-HLA antibodies (DSA)

    DSA as measured by Luminex

    Measured: 24 months

  15. Difference in illness perception at 0, 12 and 24 months and changes from baseline

    Questionnaire: Brief Illness Perception Questionnaire

    Measured: 24 months

  16. Difference in adherence of immunosuppressive medication at 12 and 24 months

    Questionnaire: Basel Assessment of Adherence to Immunosuppressive Medication Scale

    Measured: 24 months

  17. Difference in symptoms at 0, 12 and 24 months and changes from baseline

    Questionnaire: Dialysis Symptom Index with additional items from the Modified Transplant Symptom Occurrence and Symptom Distress Scale-59

    Measured: 24 months

  18. Difference in iBOX predicted outcome at 3, 5 and 7 years

    Based on the available data

    Measured: 24 months

  19. Development of a pharmacokinetic model for tacrolimus once-daily (Envarsus®), using data on AUC's

    In addition to trough levels, additional AUC's will be withdrawn at the Leiden University Medical Center as routine patient care on week 2 and 6.

    Measured: 24 months

  20. o evaluate the response to the COIVD-19 vaccine and identify possible differences between both treatment groups at the University Medical Center Groningen.

    Humoral and T-cell response

    Measured: 24 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Jan 2019
  2. Study start29 Jul 2019
  3. Primary completionJun 2025 (estimated)
  4. Study completionDec 2026 (estimated)

Resources

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
374 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03797196
Sponsor's protocol ID
OPTIMIZE
Acronym
OPTIMIZE
Status last verified
May 2023
First submitted
11 Dec 2018
Last updated
10 May 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Sanders JF, de Boer SE, Jonker J, Bemelman FJ, Betjes MGH, de Vries APJ, Hilbrands L, Hilhorst M, Kuypers DRJ, Vart P, van Zuilen AD, Hesselink DA, Berger SP. Immunosuppression in Older Kidney Transplant Recipients: A Randomized Controlled Trial. J Am Soc Nephrol. 2026 Apr 1;37(4):814-824. doi: 10.1681/ASN.0000000924. Epub 2025 Nov 7.

    PubMed 41201871

  • Oliveras L, Lopez-Vargas P, Melilli E, Codina S, Royuela A, Coloma Lopez A, Fava A, Manonelles A, Couceiro C, Lloberas N, Cruzado JM, Montero N. Delayed initiation or reduced initial dose of calcineurin-inhibitors for kidney transplant recipients at high risk of delayed graft function. Cochrane Database Syst Rev. 2025 Apr 8;4(4):CD014855. doi: 10.1002/14651858.CD014855.pub2.

    PubMed 40197799

  • de Boer SE, Sanders JSF, Bemelman FJ, Betjes MGH, Burgerhof JGM, Hilbrands L, Kuypers D, van Munster BC, Nurmohamed SA, de Vries APJ, van Zuilen AD, Hesselink DA, Berger SP. Rationale and design of the OPTIMIZE trial: OPen label multicenter randomized trial comparing standard IMmunosuppression with tacrolimus and mycophenolate mofetil with a low exposure tacrolimus regimen In combination with everolimus in de novo renal transplantation in Elderly patients. BMC Nephrol. 2021 Jun 2;22(1):208. doi: 10.1186/s12882-021-02409-8.

    PubMed 34078323

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing low dose tacrolimus in combination with everolimus and standard dose tacrolimus with mycophenolate mofetil in people with Renal Transplant Recipients and Elderly Patients, run by University Medical Center Groningen at 7 sites in 2 countries.

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 19 inclusion and 0 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: under way, not looking for participants, as of the sponsor's last update on 10 May 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in Netherlands, Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.

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?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

successful transplantation (time frame: 24 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03797196, which also lists 3 linked publications.

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 10 May 2023.

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