rATG Versus rATG Combined With IVIG Induction Immunosuppression in HLA Incompatible Transplantation
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 17
- 试验地点
- 1
- 主要终点
- Combined endpoint defined as biopsy proven antibody mediated changes (Banff 2017, Category 2) and/or TCMR (Banff 2017, Category 4) regardless the biopsy indication (for cause or protocol biopsy) in HLAi (HLA incompatible)kidney transplantation
研究概览
简要总结
This study aims to prove similar efficacy of PE/rATG (intervention) and PE/rATG/IVIG (centre standard of care) induction regimens to prevent biopsy proven antibody-mediated changes and TCMR as composite endpoint within 12 months after HLA incompatible kidney transplantation.
详细描述
There have been no published clinical studies evaluating rATG/IVIG induction protocol in comparison with rATG alone in defined cohort of HLA incompatible kidney transplant recipients. Prescribing IVIG in management of prevention of transplant rejection is considered off-label use, however IVIG remains part of induction protocols in many transplant centres. IVIG therapy is demanding due to high cost and limited resources of these human origin products. Trial participants will be end-stage renal disease (ESRD) patients listed for deceased donor / living donor kidney transplantation with anti HLA antibody screening performed within 12 months before transplantation and with last DSA 1 000 - 5 000 Mean Fluorescence Intensity (MFI) and negative CDC (Complement-dependent cytotoxicity crossmatch test) prior to transplantation. Participants will be randomized into one of the treatment groups (PE/PP(Plasmapheresis) + rATG + IVIG, PE/PP + rATG) and as a primary outcome a composite endpoint defined as occurrence of antibody- or T-cell mediated rejection within 12 months after transplantation will be evaluated.
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Primary deceased donor or living donor kidney transplantation (first transplantation or re-transplantation)
- •Recipient age ≥ 18 years and < 70 years
- •Donor age < 70 years
- •Written Informed Consent and Consent for Processing Personal Data
- •Last anti-HLA screening no longer than 12 months with positive results
- •MFI DSA 1 000 - 5 000 (anti-HLA A, B, DR), MFI DSA 1000-15000 for anti DQ when available at randomization)
排除标准
- •Combined kidney transplantation with another organ
- •Immunosuppressive therapy up to 6 months before transplantation
- •AB0i (AB0 incompatible) transplantation
- •Women in childbearing potential without adequate contraception
- •HIV positivity
- •Leukopenia < 3 000, thrombocytopenia < 75 000
- •Tuberculosis history
- •Anti-HCV (Hepatitis C Virus) positivity, HBsAg (Hepatitis B Surface Antigen) positivity or HBV (Hepatitis B Virus) DNA positivity
- •DSA (anti A, B, DR) measured by Luminex with MFI > 5 000 known at screening prior to transplant, anti DQ > 15000 if known
- •FACS (flow-cytometry) T and B crossmatch positivity known at screening prior to transplant
- •Positive CDC prior to transplantation
- •Planned PP/PE and RTX (Rituximab) treatment post-transplant
- •Advanced liver disease (Child-Pugh C or laboratory values of ALT or AST more than 3 times upper limit of normal range)
- •Pregnancy, breastfeeding
- •Study medication is contraindicated according to the SmPC
- •Patient is enrolled in other clinical trial
研究组 & 干预措施
PE/rATG
Study participants will undergo therapeutic plasma exchange (PE, 1 plasma volume) before the transplant surgery and receive rATG (Thymoglobuline®) induction (1.5 mg/kg intraoperatively and 1 mg/kg when possible daily within first week up to cumulative dose 5-7 mg/kg).
干预措施: Thymoglobulin (Drug)
PE/rATG
Study participants will undergo therapeutic plasma exchange (PE, 1 plasma volume) before the transplant surgery and receive rATG (Thymoglobuline®) induction (1.5 mg/kg intraoperatively and 1 mg/kg when possible daily within first week up to cumulative dose 5-7 mg/kg).
干预措施: Plasma Exchange (Other)
PE/rATG/IVIG
Study participants will undergo therapeutic plasma exchange (PE, 1 plasma volume) before the transplant surgery and receive rATG (Thymoglobuline®) induction (1.5 mg/kg intraoperatively and 1 mg/kg when possible daily within first week up to cumulative dose 5-7 mg/kg) and IVIG 0.5g/kg intravenous infusions, on 1st, 3rd and 5th postoperative day. This is a center standard of care regimen.
干预措施: Privigen (Drug)
PE/rATG/IVIG
Study participants will undergo therapeutic plasma exchange (PE, 1 plasma volume) before the transplant surgery and receive rATG (Thymoglobuline®) induction (1.5 mg/kg intraoperatively and 1 mg/kg when possible daily within first week up to cumulative dose 5-7 mg/kg) and IVIG 0.5g/kg intravenous infusions, on 1st, 3rd and 5th postoperative day. This is a center standard of care regimen.
干预措施: Thymoglobulin (Drug)
PE/rATG/IVIG
Study participants will undergo therapeutic plasma exchange (PE, 1 plasma volume) before the transplant surgery and receive rATG (Thymoglobuline®) induction (1.5 mg/kg intraoperatively and 1 mg/kg when possible daily within first week up to cumulative dose 5-7 mg/kg) and IVIG 0.5g/kg intravenous infusions, on 1st, 3rd and 5th postoperative day. This is a center standard of care regimen.
干预措施: Plasma Exchange (Other)
结局指标
主要结局
Combined endpoint defined as biopsy proven antibody mediated changes (Banff 2017, Category 2) and/or TCMR (Banff 2017, Category 4) regardless the biopsy indication (for cause or protocol biopsy) in HLAi (HLA incompatible)kidney transplantation
时间窗: 12 months
Number of biopsy-confirmed rejections
次要结局
- Incidence of active antibody-mediated rejection (ABMR) lesions within 12 months post-transplantation(12 months)
- Time to active antibody-mediated rejection (ABMR) within 12 months post-transplantation(12 months)
- Incidence of chronic active antibody-mediated rejection (ABMR) and C4d staining without evidence of rejection in protocol biopsies at Month 3 and Month 12(3 and 12 months)
- Incidence of transplant glomerulopathy (TG) in protocol biopsies at Month 3 and Month 12(3 and 12 months)
- Incidence of acute T-cell mediated rejection (TCMR) and chronic active TCMR in protocol biopsies at Month 3 and Month 12 post-transplantation(3 and 12 months)
- Estimated glomerular filtration rate (eGFR) at Month 3, Month 6 and Month 12(3, 6 and 12 months)
- Measured proteinuria and albuminuria at Month 3, Month 6 and Month 12(3, 6 and 12 months)
- Donor specific antibodies (DSA) at Month 3, Month 6 and Month12(3, 6 and 12 months)
- De novo donor specific antibodies (DSA) at Month 3, Month 6 and Month 12(3, 6 and 12 months)
- Mortality rate within 12 months post-transplantation(12 months)
- Graft survival (rate of graft loss) within 12 months post transplantation(12 months)
- Incidence of metabolic, malignant and cardiovascular co-morbidities(12 months)
- Incidence of viral and bacterial complications(12 months)
- Incidence of BK Virus (BKV), Cytomegalovirus (CMV) and Epstein-Barr Virus (EBV) replications detected by PCR (polymerase chain reaction) at Month 3, Month 6 and Month 12(3, 6 and 12 months)
- Incidence of study treatment discontinuation(12 months)
- Incidence of molecular rejection in the 12-month protocol biopsies(12 months)
研究者
Prof. Ondřej Viklický, M.D., Ph.D.
Head of Department of Nephrology and Transplant Center
Institute for Clinical and Experimental Medicine