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A prospective, single center, randomized study comparing the efficacy and safety of the addition of everolimus to tacrolimus/mycophenolate mofetil/predinisone in kidney transplanted recipients HLA-sensitized

Grant number: 17/19339-9
Support type:Research Projects - Thematic Grants
Duration: August 01, 2019 - July 31, 2024
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Elias David-Neto
Grantee:Elias David-Neto
Home Institution: Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
Assoc. researchers: Carlucci Gualberto Ventura ; Clarisse Martins Machado ; Nelson Zocoler Galante ; Patrícia Soares de Souza ; Sueli Mieko Oba Shinjo ; Suely Kazue Nagahashi Marie ; Verônica Porto Carreiro de Vasconcellos Coelho

Abstract

Sensitized patients to HLA (Class I or II PRA e 10%) represents 20-25% of renal transplanted patient. They are usually over immunosuppressed to prevent rejection and therefore develop more infections like CMV disease. There is no current immunosuppressive regimen that addresses the demands for these patients. We hypothesize that adding everolimus, an mTOR inhibitor with different site of action and a role in CMV prevention to the tacrolimus/mycophenolic acid/steroids, we will reduce the incidence of acute rejection and prevent CMV disease. We also do not expect more serious adverse events due to the reduced level of all 4 drugs. To design this study, we previously performed a proof-of-concept pilot study with 24 patients and observed a reduction in acute rejection rate (50 vs 10%, p= 0.001) and lower levels of CMV viremia in the quadruple group compared to the triple therapy group. The aim of this study is to develop a clinical trial with a planned sample size for the primary objective and at the same time analyze some mechanisms (anti-HLA antibodies dynamics, CMV-specific T-cell immunity, differences in peripheral lymphocyte sub-populations, genes expressions in renal biopsies and the correlations of pharmacokinetics of these drugs with all events) involved in the observed efficacy of the pilot study. (AU)