Clinical trial NCT01354301: Efficacy and Safety of Induction Strategies Combined With Low Tacrolimus Exposure in Kidney Transplant Recipients Receiving Everolimus or Sodium Mycophenolate
Official title: Efficacy and Safety of Induction Strategies Combined With Low Tacrolimus Exposure in Kidney Transplant Recipients Receiving Everolimus or Sodium Mycophenolate
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Cytomegalovirus Infection
Renal Transplant Failure
Transplant; Complication, Rejection
Keywords: kidney transplantation
thymoglobulin
everolimus
Lead sponsor: Hospital do Rim e Hipertensão
Sponsor class: OTHER
First posted: 2011-05-16
Enrollment: 300
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: Despite the improvement of efficacy results with current immunosuppressive regimens (about 15% of incidence of acute rejection), the security schemes used do not show the same results.The most worldwide used regime is tacrolimus, mycophenolate and prednisone. Despite the favorable efficacy results in our population, the use of this combination is associated with higher incidence of viral infections such as cytomegalovirus, and gastrointestinal events, two common causes of hospital readmissions after renal transplantation at our institution.Given this, the investigators propose a study of our own initiative that attends our local needs: identify the best strategy among the therapeutic options available to maintain the result of current effectiveness and improve the safety profile for kidney transplant recipients.This protocol is a prospective, randomized, single center, designed to compare the safety and efficacy of three immunosuppressive regimens: (1) single dose of antithymocyte globulin, reduced exposure to tacrolimus, everolimus starting on day 2 after transplantation and prednisone; ( 2) basiliximab, reduced exposure to tacrolimus, everolimus starting on day 2 after transplantation and prednisone; (3-control group) basiliximab, reduced exposure to tacrolimus, mycophenolate and prednisone.Our hypothesis is that a single dose of antithymocyte globulin or basiliximab induction therapy in combination with low doses of tacrolimus, everolimus and prednisone results in comparable efficacy observed in patients receiving tacrolimus / mycophenolate / prednisone, but with a better safety profile.

To ensure efficacy, the investigators added to the regimes the induction with monoclonal or polyclonal antibody. To improve the toxicities associated with the current scheme, the investigators replace the use of mycophenolate by everolimus and the investigators reduced the dose of tacrolimus.

Patients will be monitored for blood levels of tacrolimus and everolimus to ensure adequate exposure to immunosuppressive agents.

Detailed description: Primary end-point: The incidence of CMV infection or disease during the first year of transplantation.Secondary main end-point: the incidence of treatment failure defined as a composite end-point of BCAR, graft loss, death, loss to follow up.

The investigators anticipate enrolling 300 patients within 12 months. Only low risk adult candidates for first renal transplants from living or deceased donors will be considered for enrollment. Patients will be excluded if they have been receiving immunosuppressive therapy before transplantation; have received an investigational medication within the past 30 days; have a known contraindication to the administration of antithymocyte globulin; if tested positive for human immunodeficiency virus (HIV); if had had cancer (except nonmelanoma skin cancer) within the previous 2 years. Pregnant women, nursing mothers, and women of childbearing potential who will be not using condoms or oral contraceptives will be excluded. Patients with any panel reactive antibody (PRA) equal to or above 50%, class I or class II, will also be excluded. Study visits will be performed at pre transplant, days 0, 1, 7, every week up to month 6 and month 12.

Eligibility criteria: Inclusion Criteria:

* low risk adult candidates for first renal transplants from living or deceased donors

Exclusion Criteria:

* receiving immunosuppressive therapy before transplantation;
* have received an investigational medication within the past 30 days;
* have a known contraindication to the administration of antithymocyte globulin;
* tested positive for human immunodeficiency virus (HIV);
* had had cancer (except nonmelanoma skin cancer) within the previous 2 years;
* Pregnant women, nursing mothers, and women of childbearing potential who will be not using condoms or oral contraceptives will be excluded;
* Patients with any panel reactive antibody (PRA) equal to or above 50%, class I or class II.

Primary outcomes:
measure: incidence of CMV infection or disease
timeFrame: 1 year
Secondary outcomes:
measure: incidence of treatment failure defined as a composite end-point of BCAR, graft loss, death, loss to follow up.
timeFrame: 1 year
Other outcomes:
Locations:
city: Sao Paulo
country: Brazil
facility: Hospital do rim e Hipertensao
Study officials:
affiliation: Hospital do Rim e Hipertensão - Fundação Oswaldo Ramos
name: Hélio Tedesco, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Nunes Ficher K, Dreige Y, Gessolo Lins PR, Nicolau Ferreira A, Toniato de Rezende Freschi J, Linhares K, Stopa Martins S, Custodio L, Cristelli M, Viana L, Wagner Santos D, de Marco R, Gerbase-DeLima M, Proenca H, Aguiar W, Nakamura M, Rosso Felipe C, Medina Pestana J, Tedesco Silva H Jr. Long-term Efficacy and Safety of Everolimus Versus Mycophenolate in Kidney Transplant Recipients Receiving Tacrolimus. Transplantation. 2022 Feb 1;106(2):381-390. doi: 10.1097/TP.0000000000003714.
citation: Tedesco-Silva H, Felipe C, Ferreira A, Cristelli M, Oliveira N, Sandes-Freitas T, Aguiar W, Campos E, Gerbase-DeLima M, Franco M, Medina-Pestana J. Reduced Incidence of Cytomegalovirus Infection in Kidney Transplant Recipients Receiving Everolimus and Reduced Tacrolimus Doses. Am J Transplant. 2015 Oct;15(10):2655-64. doi: 10.1111/ajt.13327. Epub 2015 May 18.