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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Helio Tedesco Silva Junior, Hospital do Rim e Hipertensão
ClinicalTrials.gov Identifier:
NCT01354301
First received: May 13, 2011
Last updated: June 28, 2013
Last verified: June 2013
  Purpose

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.


Condition Intervention Phase
Cytomegalovirus Infection
Renal Transplant Failure
Transplant; Complication, Rejection
Drug: Thymoglobulin
Drug: Everolimus
Drug: Basiliximabe
Drug: mycophenolate sodium
Drug: Tacrolimus
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Efficacy and Safety of Induction Strategies Combined With Low Tacrolimus Exposure in Kidney Transplant Recipients Receiving Everolimus or Sodium Mycophenolate

Resource links provided by NLM:


Further study details as provided by Hospital do Rim e Hipertensão:

Primary Outcome Measures:
  • incidence of CMV infection or disease [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • incidence of treatment failure defined as a composite end-point of BCAR, graft loss, death, loss to follow up. [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Estimated Enrollment: 300
Study Start Date: May 2011
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Thymoglobulin and everolimus
single dose antithymocyte globulin, reduced concentration tacrolimus, everolimus starting at day 2 posttransplant and prednisone
Drug: Thymoglobulin
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.
Drug: Everolimus
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.
Drug: Tacrolimus
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.
Experimental: Basiliximabe and everolimus
basiliximab, reduced concentration tacrolimus, everolimus starting at day 2 posttransplant and prednisone
Drug: Everolimus
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.
Drug: Basiliximabe
days 0 and 4, according to the package insert instructions.
Drug: Tacrolimus
0.1 mg/kg BID beginning on day 1. Doses will be adjusted to maintain tacrolimus whole blood trough concentrations between 3-8 ng/ml and 3-5 ng/ml after 3 months.
Active Comparator: Basiliximabe and mycophenolate
basiliximab, reduced concentration tacrolimus, mycophenolate and prednisone.
Drug: Basiliximabe
days 0 and 4, according to the package insert instructions.
Drug: mycophenolate sodium
720 mg BID. This dose will be reduced according to adverse events.
Drug: Tacrolimus
0.1 mg/kg BID beginning on day 1. Doses will be adjusted to maintain tacrolimus whole blood trough concentrations between 3-8 ng/ml.

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01354301

Locations
Brazil
Hospital do rim e Hipertensao
Sao Paulo, Brazil, 04038-002
Sponsors and Collaborators
Hospital do Rim e Hipertensão
Investigators
Principal Investigator: Hélio Tedesco, MD Hospital do Rim e Hipertensão - Fundação Oswaldo Ramos
  More Information

No publications provided

Responsible Party: Helio Tedesco Silva Junior, PhD, Hospital do Rim e Hipertensão
ClinicalTrials.gov Identifier: NCT01354301     History of Changes
Other Study ID Numbers: CRAD001ABR18T
Study First Received: May 13, 2011
Last Updated: June 28, 2013
Health Authority: Brazil: ANVISA
Brazil: CEP-UNIFESP

Keywords provided by Hospital do Rim e Hipertensão:
kidney transplantation
thymoglobulin
everolimus

Additional relevant MeSH terms:
Cytomegalovirus Infections
DNA Virus Infections
Herpesviridae Infections
Virus Diseases
Everolimus
Mycophenolate mofetil
Mycophenolic Acid
Sirolimus
Tacrolimus
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Antineoplastic Agents
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 23, 2014