Efficacy and Safety of Induction Strategies Combined With Low Tacrolimus Exposure in Kidney Transplant Recipients Receiving Everolimus or Sodium Mycophenolate

NCT01354301 | Completed Phase 4

• 1 other identifier: CRAD001ABR18T
• Study Type: interventional
• Target: 300
• Locations: 1 country
• Sites: 1

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.

Conditions

Cytomegalovirus Infection; Renal Transplant Failure; Transplant; Complication, Rejection

Keywords

kidney transplantation; thymoglobulin; everolimus

Outcome Measures

Primary Outcomes (1)

• incidence of CMV infection or disease

  1 year

Secondary Outcomes (1)

• incidence of treatment failure defined as a composite end-point of BCAR, graft loss, death, loss to follow up.

  1 year

Study Arms (3)

Thymoglobulin and everolimus

EXPERIMENTAL

single dose antithymocyte globulin, reduced concentration tacrolimus, everolimus starting at day 2 posttransplant and prednisone

Drug: Thymoglobulin; Drug: Everolimus; Drug: Tacrolimus

Basiliximabe and everolimus

EXPERIMENTAL

basiliximab, reduced concentration tacrolimus, everolimus starting at day 2 posttransplant and prednisone

Drug: Everolimus; Drug: Basiliximabe; Drug: Tacrolimus

Basiliximabe and mycophenolate

ACTIVE COMPARATOR

basiliximab, reduced concentration tacrolimus, mycophenolate and prednisone.

Drug: Basiliximabe; Drug: mycophenolate sodium; Drug: Tacrolimus

Interventions

Thymoglobulin DRUG

intravenously, beginning within the first 24 hours after graft revascularization. Pre-treatment includes hydrocortisone and dipyrone before antithymocyte globulin infusion, which will be reconstituted according to the package insert.

Thymoglobulin and everolimus

Everolimus DRUG

initial 0.75 mg BID dose of everolimus on day 2. Doses will be adjusted from day 5 on to maintain everolimus whole blood trough concentrations between 4-8 ng/ml.

Basiliximabe and everolimus; Thymoglobulin and everolimus

Basiliximabe DRUG

days 0 and 4, according to the package insert instructions.

Basiliximabe and everolimus; Basiliximabe and mycophenolate

mycophenolate sodium DRUG

720 mg BID. This dose will be reduced according to adverse events.

Basiliximabe and mycophenolate

Tacrolimus DRUG

0.05 mg/kg BID beginning on day 1. Doses will be adjusted to maintain tacrolimus whole blood trough concentrations between 3-5 ng/ml.

Thymoglobulin and everolimus

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Hospital do Rim e Hipertensão: lead

Study Sites (1)

Hospital do rim e Hipertensao

São Paulo, São Paulo, 04038-002, Brazil

Location

Related Publications (2)

• 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.

  PMID: 33988338 DERIVED

• 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.

  PMID: 25988935 DERIVED

MeSH Terms

Conditions

Cytomegalovirus Infections; Rejection, Psychology

Interventions

thymoglobulin; Everolimus; Mycophenolic Acid; Tacrolimus

Condition Hierarchy (Ancestors)

Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Social Behavior; Behavior

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids

Study Officials

• Hélio Tedesco, MD

  Hospital do Rim e Hipertensão - Fundação Oswaldo Ramos

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PhD

Study Record Dates

• First Submitted: May 13, 2011
• First Posted: May 16, 2011
• Study Start: May 1, 2011
• Primary Completion: April 1, 2014
• Study Completion: December 1, 2014
• Last Updated: March 23, 2015

Record last verified: 2015-03

Locations

BR (1)