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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

May 13, 2011
June 28, 2013
May 2011
April 2014   (final data collection date for primary outcome measure)
incidence of CMV infection or disease [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
Same as current
Complete list of historical versions of study NCT01354301 on ClinicalTrials.gov Archive Site
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 ]
Same as current
Not Provided
Not Provided
 
Efficacy and Safety of Induction Strategies Combined With Low Tacrolimus Exposure in Kidney Transplant Recipients Receiving Everolimus or Sodium Mycophenolate
Efficacy and Safety of Induction Strategies Combined With Low Tacrolimus Exposure in Kidney Transplant Recipients Receiving Everolimus or Sodium Mycophenolate

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.

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.

Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Cytomegalovirus Infection
  • Renal Transplant Failure
  • Transplant; Complication, Rejection
  • 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: 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
    0.05 mg/kg BID beginning on day 1. Doses will be adjusted to maintain tacrolimus whole blood trough concentrations between 3-5 ng/ml.
  • 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.
  • 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.
  • Experimental: Thymoglobulin and everolimus
    single dose antithymocyte globulin, reduced concentration tacrolimus, everolimus starting at day 2 posttransplant and prednisone
    Interventions:
    • Drug: Thymoglobulin
    • Drug: Everolimus
    • Drug: Tacrolimus
  • Experimental: Basiliximabe and everolimus
    basiliximab, reduced concentration tacrolimus, everolimus starting at day 2 posttransplant and prednisone
    Interventions:
    • Drug: Everolimus
    • Drug: Basiliximabe
    • Drug: Tacrolimus
  • Active Comparator: Basiliximabe and mycophenolate
    basiliximab, reduced concentration tacrolimus, mycophenolate and prednisone.
    Interventions:
    • Drug: Basiliximabe
    • Drug: mycophenolate sodium
    • Drug: Tacrolimus
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
300
December 2014
April 2014   (final data collection date for primary outcome measure)

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.
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Brazil
 
NCT01354301
CRAD001ABR18T
No
Helio Tedesco Silva Junior, Hospital do Rim e Hipertensão
Hospital do Rim e Hipertensão
Not Provided
Principal Investigator: Hélio Tedesco, MD Hospital do Rim e Hipertensão - Fundação Oswaldo Ramos
Hospital do Rim e Hipertensão
June 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP