" SAVE Study (Switch AdVagraf® to Envarsus®) for Fast Metabolizers Kidney Transplant Recipients" (SAVE)

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.

Study Overview

• Status: Recruiting
• Conditions: Renal Transplant Failure
• Intervention / Treatment: Other: No intervention

• Study Type: Observational
• Enrollment (Estimated): 225

Contacts and Locations

• Study Contact: Name: Jacques DANTAL; Phone Number: (+33) 24 00 87 44 1; Email: jacques.dantal@chu-nantes.fr
• Study Contact Backup: Name: Christophe Masset; Phone Number: (+33) 27 66 43 96 1; Email: christophe.masset@chu-nantes.fr

Study Locations

• France
  • Nantes, France
    • Recruiting
    • CHU de Nantes

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• 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.

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
control; Before switch Advagraf to Envarsus	Other: No intervention; no intervention
case; After switch Advagraf to Envarsus	Other: No intervention; no intervention

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Improvement of kidney allograft between month 1 and month 12	comparison of eGFR (estimated Glomerular Filtration Rate) level at M12 by using the MDRD formula between Envarsus® and Advagraf® groups.	12 months

Collaborators and Investigators

• Sponsor: Nantes University Hospital
• Investigators: Principal Investigator: Jacques DANTAL, Nantes University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): July 28, 2021
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: June 1, 2021
• First Submitted That Met QC Criteria: June 22, 2021
• First Posted (Actual): June 30, 2021

Study Record Updates

• Last Update Posted (Actual): August 4, 2023
• Last Update Submitted That Met QC Criteria: August 3, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Other Study ID Numbers: RC20_0443

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No