RCT Comparing Immunosuppressive Regimens in Elderly Renal Transplant Recipients

NCT ID: NCT03797196

Last Updated: 2023-05-10

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 374 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-07-29
• Study Completion Date: 2026-12-31

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).

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.

Conditions

Renal Transplant Recipients; Elderly Patients; Immunosuppression

Study Design

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

Study Groups

group 1

standard tacrolimus with mycophenolate mofetil

Group Type: ACTIVE_COMPARATOR

standard dose tacrolimus with mycophenolate mofetil

Intervention Type: DRUG

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

group 2

low dose tacrolimus with everolimus

Group Type: EXPERIMENTAL

low dose tacrolimus in combination with everolimus

Intervention Type: DRUG

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

Interventions

low dose tacrolimus in combination with everolimus

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

Intervention Type: DRUG

standard dose tacrolimus with mycophenolate mofetil

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

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Written informed consent must be obtained before any assessment is performed

2. Male or female subject ≥65 years old

3. Subject randomized within 24 hours of completion of transplant surgery

4. 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

5. 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

1. Subject is a multi-organ transplant recipient

2. Recipient of bloodgroup ABO incompatible allograft or CDC cross-match positive transplant

3. Subject at high immunological risk for rejection as determined by local practice for assessment of anti-donor reactivity

4. Recipient of a kidney with a cold ischaemia time (CIT) >24 hr

5. Recipients of a kidney from an HLA-identical related living donor

6. Known intolerability for one or more of the study drugs

7. Subject who is HIV positive

8. 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

9. 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)

10. Subject with severe systemic infections, current or within the two weeks prior to randomization

11. Subject with severe restrictive or obstructive pulmonary disorders

12. Subject with severe hypercholesterolemia or hypertriglyceridemia that cannot be controlled

13. Subject with white blood cell (WBC) count ≤ 2,000/mm3 or with platelet count ≤ 50,000/mm3

• Minimum Eligible Age: 65 Years
• Maximum Eligible Age: 99 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Radboud University Medical Center

OTHER

Sponsor Role: collaborator

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

OTHER

Sponsor Role: collaborator

Amsterdam UMC, location VUmc

OTHER

Sponsor Role: collaborator

UMC Utrecht

OTHER

Sponsor Role: collaborator

Leiden University Medical Center

OTHER

Sponsor Role: collaborator

Erasmus Medical Center

OTHER

Sponsor Role: collaborator

Universitaire Ziekenhuizen KU Leuven

OTHER

Sponsor Role: collaborator

University Medical Center Groningen

OTHER

Sponsor Role: lead

Responsible Party

J.S.F. Sanders

principal investigator, head of renal transplant program UMCG

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Dennis Hesselink, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

EMC

Frederike Bemelman, Md, PhD

Role: PRINCIPAL_INVESTIGATOR

AIDS Malignancy Consortium

Stefan Berger, Md, PhD

Role: STUDY_CHAIR

UMCG

Jan-Stephan Sanders, MD, PhD

Role: STUDY_DIRECTOR

UMCG

Azam Nurmohamed, Md, PhD

Role: PRINCIPAL_INVESTIGATOR

VUMC

Aiko De Vries, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

LUMC

Luuk Hilbrands, Md, PhD

Role: PRINCIPAL_INVESTIGATOR

Radboud MC

Arjan Van Zuilen, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

UMCU

Dirk Kuypers, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Leuven MC

Locations

Leuven University Hospital

Leuven, , Belgium

Amsterdam UMC

Amsterdam, , Netherlands

UMCG

Groningen, , Netherlands

LUMC

Leiden, , Netherlands

Radboud University Hospital

Nijmegen, , Netherlands

Erasmus MC

Rotterdam, , Netherlands

UMCU

Utrecht, , Netherlands

Countries

Belgium; Netherlands

References

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.

Reference Type: DERIVED

PMID: 40197799 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 34078323 (View on PubMed)

Other Identifiers

OPTIMIZE

Identifier Type: -

Identifier Source: org_study_id