Efficacy and Safety of Induction Strategies Combined With Low Tacrolimus Exposure in Kidney Transplant Recipients Receiving Everolimus or Sodium Mycophenolate
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 300
- 试验地点
- 1
- 主要终点
- incidence of CMV infection or disease
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •low risk adult candidates for first renal transplants from living or deceased donors
排除标准
- •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.
研究组 & 干预措施
Thymoglobulin and everolimus
single dose antithymocyte globulin, reduced concentration tacrolimus, everolimus starting at day 2 posttransplant and prednisone
干预措施: Thymoglobulin (Drug)
Thymoglobulin and everolimus
single dose antithymocyte globulin, reduced concentration tacrolimus, everolimus starting at day 2 posttransplant and prednisone
干预措施: Everolimus (Drug)
Thymoglobulin and everolimus
single dose antithymocyte globulin, reduced concentration tacrolimus, everolimus starting at day 2 posttransplant and prednisone
干预措施: Tacrolimus (Drug)
Basiliximabe and everolimus
basiliximab, reduced concentration tacrolimus, everolimus starting at day 2 posttransplant and prednisone
干预措施: Everolimus (Drug)
Basiliximabe and everolimus
basiliximab, reduced concentration tacrolimus, everolimus starting at day 2 posttransplant and prednisone
干预措施: Basiliximabe (Drug)
Basiliximabe and everolimus
basiliximab, reduced concentration tacrolimus, everolimus starting at day 2 posttransplant and prednisone
干预措施: Tacrolimus (Drug)
Basiliximabe and mycophenolate
basiliximab, reduced concentration tacrolimus, mycophenolate and prednisone.
干预措施: Basiliximabe (Drug)
Basiliximabe and mycophenolate
basiliximab, reduced concentration tacrolimus, mycophenolate and prednisone.
干预措施: mycophenolate sodium (Drug)
Basiliximabe and mycophenolate
basiliximab, reduced concentration tacrolimus, mycophenolate and prednisone.
干预措施: Tacrolimus (Drug)
结局指标
主要结局
incidence of CMV infection or disease
时间窗: 1 year
次要结局
- incidence of treatment failure defined as a composite end-point of BCAR, graft loss, death, loss to follow up.(1 year)
研究者
Helio Tedesco Silva Junior
PhD
Hospital do Rim e Hipertensão