Open Label Randomized Study of Thymoglobulin Versus Daclizumab Induction Therapies for the Reduction of Acute Rejection in Live Donor Kidney Transplant Recipients With a Positive Crossmatch
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 56
- 试验地点
- 1
- 主要终点
- 6-month Cumulative Rejection Incidence (Either CMR, AMR or Both)
研究概览
简要总结
The purpose of this study is to determine whether the anti-T cell antibody, Thymoglobulin is a more effective induction medication than the anti-IL-2R inhibitor daclizumab, in kidney transplant recipients who have a positive crossmatch with their live donor.
详细描述
Kidney transplantation is widely recognized as the optimal therapy for the management of end-stage renal disease. Presently, the deceased donor kidney waiting list has expanded disproportionately with the number of transplant procedures that are performed in the United States. To further compound this problem, as many as 1/3 of the patients on this list are highly sensitized against a broad range of potential donors.
In order to address this problem, we developed an antibody depletion protocol that permits transplantation in patients who have a positive crossmatch with their live donor. The protocol consists of standard immunosuppressant therapy, plasmapheresis, and intravenous immunoglobulin infusion. We have successfully performed transplantation in over 100 such patients with low complication rates.
Because these patients have been exposed to their donor's human leukocyte antigen (HLA) they are at high risk for both acute cellular and acute antibody-mediated rejection. This intent of this prospective, randomized, open-label trial is to determine whether induction therapy (i.e. therapy given at the time of transplantation for prophylaxis) with Thymoglobulin is associated with a lower 6-month incidence of acute cellular and antibody-mediated rejection than with our standard therapy, daclizumab.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 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
- •Adult (18 years or older)
- •End-stage renal disease
- •Identified to have positive lymphocytotoxic crossmatch or flow cytometric crossmatch with live donor
排除标准
- •Deceased donor recipients
- •Pregnancy
- •Active infection
- •History of cancer within the past two years (with the exception of non-melanomatous skin cancer)
- •History of heparin induced thrombocytopenia
- •Medical contraindications to transplant procedure
研究组 & 干预措施
Thymoglobulin
Thymoglobulin was administered as 1.5 mg/kg prior to reperfusion followed by 6 post-operative doses on days 1 through 6.
干预措施: Thymoglobulin (Drug)
Thymoglobulin
Thymoglobulin was administered as 1.5 mg/kg prior to reperfusion followed by 6 post-operative doses on days 1 through 6.
干预措施: Plasmapheresis (Other)
Thymoglobulin
Thymoglobulin was administered as 1.5 mg/kg prior to reperfusion followed by 6 post-operative doses on days 1 through 6.
干预措施: Mycophenolate mofetil (Drug)
Thymoglobulin
Thymoglobulin was administered as 1.5 mg/kg prior to reperfusion followed by 6 post-operative doses on days 1 through 6.
干预措施: Tacrolimus (Drug)
Thymoglobulin
Thymoglobulin was administered as 1.5 mg/kg prior to reperfusion followed by 6 post-operative doses on days 1 through 6.
干预措施: Dexamethasone (Drug)
Thymoglobulin
Thymoglobulin was administered as 1.5 mg/kg prior to reperfusion followed by 6 post-operative doses on days 1 through 6.
干预措施: Prednisone (Drug)
Thymoglobulin
Thymoglobulin was administered as 1.5 mg/kg prior to reperfusion followed by 6 post-operative doses on days 1 through 6.
干预措施: Cytogam (Drug)
Daclizumab
Daclizumab was administered as 2 mg/kg prior to reperfusion followed by 1 mg/kg every other week for 8 weeks post-operatively (4 post-operative doses).
干预措施: Daclizumab (Drug)
Daclizumab
Daclizumab was administered as 2 mg/kg prior to reperfusion followed by 1 mg/kg every other week for 8 weeks post-operatively (4 post-operative doses).
干预措施: Plasmapheresis (Other)
Daclizumab
Daclizumab was administered as 2 mg/kg prior to reperfusion followed by 1 mg/kg every other week for 8 weeks post-operatively (4 post-operative doses).
干预措施: Mycophenolate mofetil (Drug)
Daclizumab
Daclizumab was administered as 2 mg/kg prior to reperfusion followed by 1 mg/kg every other week for 8 weeks post-operatively (4 post-operative doses).
干预措施: Tacrolimus (Drug)
Daclizumab
Daclizumab was administered as 2 mg/kg prior to reperfusion followed by 1 mg/kg every other week for 8 weeks post-operatively (4 post-operative doses).
干预措施: Dexamethasone (Drug)
Daclizumab
Daclizumab was administered as 2 mg/kg prior to reperfusion followed by 1 mg/kg every other week for 8 weeks post-operatively (4 post-operative doses).
干预措施: Prednisone (Drug)
Daclizumab
Daclizumab was administered as 2 mg/kg prior to reperfusion followed by 1 mg/kg every other week for 8 weeks post-operatively (4 post-operative doses).
干预措施: Cytogam (Drug)
结局指标
主要结局
6-month Cumulative Rejection Incidence (Either CMR, AMR or Both)
时间窗: Up to 6 months
Biopsy shows evidence of either AMR or CMR or evidence both.
6-month Acute Antibody-mediated Rejection Rate (AMR)
时间窗: Up to 6 months
A diagnosis of AMR was based on the 2013 international Banff Classification Criteria and is defined as the presence of circulating donor-specific antibody (DSA) and either: 1) peritubular capillary staining of C4d and at least one of the following: peritubular capillaritis (ptc) score\>0, glomerulitis (g) score\>0, acute thrombotic microangiopathy (TMA) in the absence of any other cause, or other features consistent with AMR (endothelial injury, fibrin thrombi, microinfarctions, interstitial hemorrhage), or 2) absence of capillary staining of C4d and the presence of ptc\>0 and g\>0 or ptc\>0 or g\>0 and acute TMA, in the absence of any other cause of TMA.
6-month Acute Cellular-mediated Rejection Rate (CMR)
时间窗: Up to 6 months
Per 2007 international Banff Classification Criteria, CMR 1A was diagnosed on biopsies displaying significant interstitial infiltration (\>25% of parenchyma affected, i2 or i3) and foci of moderate tubulitis (t2). CMR IB was diagnosed in cases with significant interstitial infiltration (\>25% of parenchyma affected, i2 or i3) and foci of severe tubulitis (t3). CMR IIA were cases with mild-to-moderate intimal arteritis (v1), while CMR IIB were those with severe intimal arteritis comprising \>25% of the luminal area (v2). CMR III were those cases with transmural arteritis and/or arterial fibrinoid change and necrosis of medial smooth muscle cells with accompanying lymphocytic inflammation (v3).
次要结局
未报告次要终点