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

Cytomegalovirus Infection Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01354301
• Other study ID #: CRAD001ABR18T
• Status: Completed
• Phase: Phase 4
• First received: May 13, 2011
• Last updated: March 20, 2015
• Start date: May 2011
• Est. completion date: December 2014

Study information

• Verified date: March 2015
• Source: Hospital do Rim e Hipertensão
• Contact: n/a
• Is FDA regulated: No
• Health authority: Brazil: ANVISABrazil: CEP-UNIFESP
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 300
• Est. completion date: December 2014
• Est. primary completion date: April 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

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

Intervention

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.
• 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.
• Basiliximabe
days 0 and 4, according to the package insert instructions.
• mycophenolate sodium
720 mg BID. This dose will be reduced according to adverse events.
• 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.
• 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.
• 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.

Locations

Country	Name	City	State
Brazil	Hospital do rim e Hipertensao	Sao Paulo

Sponsors (1)

Lead Sponsor	Collaborator
Hospital do Rim e Hipertensão

Country where clinical trial is conducted

Brazil, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	incidence of CMV infection or disease		1 year	Yes
Secondary	incidence of treatment failure defined as a composite end-point of BCAR, graft loss, death, loss to follow up.		1 year	No