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 Opportunities: Research Projects - Thematic Grants
• Start date: August 01, 2019
• End date: July 31, 2025
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Elias David-Neto
• Grantee: Elias David-Neto
• Host Institution: Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Associated 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
• Associated scholarship(s): 20/13282-8 - Pharmacokinetics of Micofenolato Mofetil in combination with Tacrolimus and Everolimo in kidney transplant patients, BP.IC; 20/07714-2 - Monitoring safety profile of the addiction of everolimus to the immunosuppression based in tacrolimus, mycophenolate mofetil and prednisone in HLA sensitized kidney transplant recipients, BP.IC

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)