Clinical trial NCT04945785: " SAVE Study (Switch AdVagraf® to Envarsus®) for Fast Metabolizers Kidney Transplant Recipients"
Official title: " SAVE Study (Switch AdVagraf® to Envarsus®) for Fast Metabolizers Kidney Transplant Recipients"
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Renal Transplant Failure
Lead sponsor: Nantes University Hospital
Sponsor class: OTHER
First posted: 2021-06-30
Enrollment: 225
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CROSSOVER
Time perspective: CROSS_SECTIONAL
Sampling method: PROBABILITY_SAMPLE
Study population: Major patients with row 1 or 2 renal transplants (1st or 2nd transplant) rapid metabolizers defined by a C0 / D ratio \<1.05 at one month post transplant, with impaired function of the graft. 75 patients will be prospectively included in the Advagraf® or Prograf® switch cohort for Envarsus® during their renal transplant follow-up. 150 patients matched on age, graft rank, type of donor (standard criteria / expanded criteria) and C0 / D at one month of grafting will constitute the retrospective control cohort extracted from the database in Nantes.

Brief summary: The use of calcineurin inhibitors (CNIs) in kidney transplantation is the gold standard treatment to prevent episodes of rejection. Nevertheless, CNIs have side effects and are in particular nephrotoxic for the kidney transplant. Monitoring CNI dosages is fundamental for the clinician, in order to find the right balance between toxicity and prevention of rejection. Several recent studies suggest that a Radio Residual Concentration / Dosage (C0 / D) less than 1.05 (patients with rapid metabolizers) is associated with poor graft function (eGFR) and decreased kidney transplant survival. LCPT prolonged-release tacrolimus (Novel Once-Daily Extended-Release Tacrolimus. Prolonged-release tacrolimus: Envarsus®) is a marketed form of tacrolimus with interesting pharmacokinetic properties: daily intake, reduction of the absorption peak (Meltodose® technology ) and reduction of the total CNI dose by 30% to obtain an equivalent CO compared to other molecules on the market (Advagraf®, Prograf®). Thus, the use of LCPT in patients rapid metabolisers in relay of Advagraf® or Prograf® could make it possible to decrease renal toxicity while preserving rejection, by increasing the C0 / D ratio.

The investigators propose a pilot study aiming to study a prospective cohort of rapid metabolisers patients put on Envarsus at one month of transplant compared to a historical cohort, in terms of C0 / D ratio, function and survival of the renal graft.


Eligibility criteria: Inclusion Criteria:

* Patient ≥ 18 years old
* 1st or 2nd kidney transplant
* Transplantation from a deceased donor (Encephalic death or arrested heart Maastricht III) or living donor
* C0 / D ratio \<1.05 at one month of kidney transplant
* Renal graft function \<60ml / min (eGFR estimate by CKD-EPI or MDRD).

Exclusion Criteria:

* Patient ≤ 18 years old, under guardianship or protected
* Graft rank ≥ 3
* Renal graft function \<30 ml / min (eGFR estimate by CKD-EPI or MDRD)
* Presence of pre-transplant DSA (threshold\> 2000 MFI)
* Occurrence of histologically proven rejection during the 1st month of transplant
* Presence of another functional transplant (heart / lung / liver / pancreas) or kidney bi-transplant
* Transplantation from a living donor
* Transplantation from an arrested heart donor Maastricht II

Primary outcomes:
measure: Improvement of kidney allograft between month 1 and month 12
timeFrame: 12 months
Secondary outcomes:
Other outcomes:
Locations:
city: Nantes
country: France
facility: CHU de Nantes
Study officials:
affiliation: Nantes University Hospital
name: Jacques DANTAL
role: PRINCIPAL_INVESTIGATOR
References: