Clinical trial NCT06235892: Tacrolimus Minimization in Kidney Transplant Recipients Selected According to the AGORA Algorithm for Their Low Immunological Risk and Medium-term Graft Failure
Official title: Prospective, Multicenter, Randomized, Open-label, Parallel-group Controlled Phase 3 Study of Tacrolimus Minimization in Kidney Transplant Recipients Selected According to the AGORA Algorithm for Their Low Immunological Risk and Medium-term Graft Failure
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Organ Grafts
Keywords: Tacrolimus minimization
kidney transplant
AGORA Algorithm
Lead sponsor: Nantes University Hospital
Sponsor class: OTHER
First posted: 2024-02-01
Enrollment: 332
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The goal of this clinical trial is that validation of the non-invasive biomarkers of the AGORA algorithm should make it possible to select patients with a very low immunological risk of graft failure to authorize safe minimization of their immunosuppression for adult patients at one-year post kidney transplantation.

The main question of the AGORAC trial is to demonstrate the impact of TACROLIMUS minimization using AGORA algorithm compared to standard of care on the kidney function 18 months after the minimization period.


Eligibility criteria: Inclusion Criteria:

* First kidney transplantation
* Living or brain death or
* Donation after circulatory death (Maastricht 3) donor,Compatible for ABO group with the donor,
* cPRA (Panel Reactive Antibody Calculated ) (or TGI: Incompatible Graft Rate )\<20% on the day of the transplantation and no DSA (MFI \<500) at pre transplant and at the time of the inclusion at one-year post transplantation (between 350 and 515 days after the transplantation.
* Eplet Mismatchs \<= 14
* Normal or IFTA 1-2 histology on one-year surveillance biopsy.
* Patient insured under a health insurance scheme, according to national regulation.
* Patient (of childbearing age) with effective contraception.
* Patients treated with Tacrolimus (Prograf® or Advagraf®) and MMF / MPS (Mycophenolate Sodium) +/- Corticosteroid (CS)

Exclusion Criteria:

* Donation after circulatory death maastricht 2 (uncontrolled) and maastricht 1
* Pregnant women (serum or urine test), breastfeeding women
* Patient under legal protection (incl. under guardianship or trusteeship)
* Participation to a drug interventional study within 1 month prior to the inclusion
* Any retransplantation and combined transplantations and also other organ previous transplantations
* History of lymphoproliferative disorders
* Diagnosis of a malignant disease (according to the type of malignancy)
* Hepatitis C antibody or hepatitis B surface antigen (HbsAg) positive patient or HIV infection

Primary outcomes:
measure: Improvement of the renal function at 18 months after "ultra" minimization of Tacrolimus
timeFrame: Month 18
Secondary outcomes:
measure: Incidence of biopsy-proven acute rejection (BPAR) according to the 2017 Banff classification (including borderline lesions)
timeFrame: Month 18
measure: Type, severity and treatment of biopsy-proven acute rejection ( BPAR)
timeFrame: Month 18
measure: Appearance of de novo donor-specific alloantibody (DSA) (4 digits and MFI treshold >500)
timeFrame: Month 18
measure: Appearance or worsening of histological lesions of interstitial fibrosis and inflammatory tubular atrophy (IFTA) of study biopsy by considering that only patients with normal histology or with an IFTA-1 or 2will be randomized
timeFrame: Month 18
measure: Prevalence of death, and graft loss (dialysis start or retransplantation) at end of study
timeFrame: Month 18
measure: Prevalence of metabolic disorders: post-transplant diabetes mellitus (PTDM), dyslipidaemia and hypertension at end of study
timeFrame: Month 18
measure: Treatment adherence consisting in monitoring immunosuppression adherence using Trackyourmed® to monitor individual variability tacrolimus intake
timeFrame: Month 18
measure: Change in quality of life estimated using the EQ-5D ( EuroQol instrument - dimensions) questionnaire fulfilled by patients at baseline, Month 3, Month 6, Month 9, Month 12, Month15 and Month18
timeFrame: Month 3, Month 6, Month 9, Month 12, Month15 and Month18
Other outcomes:
Locations:
city: Nantes
country: France
facility: CHU de NANTES
city: Oslo
country: Norway
facility: Oslo University Hospital
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
Study officials:
References: