RCT Comparing Immunosuppressive Regimens in Elderly Renal Transplant Recipients

NCT03797196 | Active Not Recruiting Phase 4 DMC

• 1 other identifier: OPTIMIZE
• Study Type: interventional
• Target: 374
• Locations: 2 countries
• Sites: 7

Brief 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. 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).

Conditions

Renal Transplant Recipients; Elderly Patients; Immunosuppression

Outcome Measures

Primary Outcomes (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

  24 months

Secondary Outcomes (20)

• death

  24 months

• graft loss

  24 months

• acute rejection

  24 months

• eGFR

  12 and 24 months

• type of rejection treatment

  24 months

Other Outcomes (1)

• Evaluation of Cost-effectiveness of the new immunosuppressive regimen, and comparison to the current standard of care

  24 months

Study Arms (2)

group 1

ACTIVE COMPARATOR

standard tacrolimus with mycophenolate mofetil

Drug: standard dose tacrolimus with mycophenolate mofetil

group 2

EXPERIMENTAL

low dose tacrolimus with everolimus

Drug: low dose tacrolimus in combination with everolimus

Interventions

low dose tacrolimus in combination with everolimus DRUG

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

group 2

standard dose tacrolimus with mycophenolate mofetil DRUG

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

group 1

Eligibility Criteria

• Age: 65 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University Medical Center Groningen: lead
• Radboud University Medical Center: collaborator
• Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA): collaborator
• Amsterdam UMC, location VUmc: collaborator
• UMC Utrecht: collaborator
• Leiden University Medical Center: collaborator
• Erasmus Medical Center: collaborator
• Universitaire Ziekenhuizen KU Leuven: collaborator

Study Sites (7)

Leuven University Hospital

Leuven, Belgium

Location

Amsterdam UMC

Amsterdam, Netherlands

Location

UMCG

Groningen, Netherlands

Location

LUMC

Leiden, Netherlands

Location

Radboud University Hospital

Nijmegen, Netherlands

Location

Erasmus MC

Rotterdam, Netherlands

Location

UMCU

Utrecht, Netherlands

Location

Related Publications (3)

• 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. 2025 Nov 7. doi: 10.1681/ASN.0000000924. Online ahead of print. No abstract available.

  PMID: 41201871 DERIVED

• 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.

  PMID: 40197799 DERIVED

• 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.

  PMID: 34078323 DERIVED

MeSH Terms

Interventions

Tacrolimus; Everolimus; Mycophenolic Acid

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals; Sirolimus; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids

Study Officials

• Dennis Hesselink, MD, PhD

  EMC

  PRINCIPAL INVESTIGATOR

• Frederike Bemelman, Md, PhD

  AIDS Malignancy Consortium

  PRINCIPAL INVESTIGATOR

• Stefan Berger, Md, PhD

  University Medical Center Groningen

  STUDY CHAIR

• Jan-Stephan Sanders, MD, PhD

  University Medical Center Groningen

  STUDY DIRECTOR

• Azam Nurmohamed, Md, PhD

  VUMC

  PRINCIPAL INVESTIGATOR

• Aiko De Vries, MD, PhD

  LUMC

  PRINCIPAL INVESTIGATOR

• Luuk Hilbrands, Md, PhD

  Radboud MC

  PRINCIPAL INVESTIGATOR

• Arjan Van Zuilen, MD, PhD

  UMCU

  PRINCIPAL INVESTIGATOR

• Dirk Kuypers, MD, PhD

  Leuven MC

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: principal investigator, head of renal transplant program UMCG

Study Record Dates

• First Submitted: December 11, 2018
• First Posted: January 9, 2019
• Study Start: July 29, 2019
• Primary Completion: June 1, 2025
• Study Completion (Estimated): December 1, 2026
• Last Updated: May 10, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1); NL (6)