Randomized Controlled Trial of Infliximab (Remicade®) Induction Therapy for Deceased Donor Kidney Transplant Recipients (CTOT-19)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 290
- 试验地点
- 15
- 主要终点
- The Difference Between the Mean eGFR (Modified MDRD) in the Experimental vs. Control Groups.
研究概览
简要总结
During transplant surgery, there is a period of time when a donated kidney is removed from a donor's body and stored until the time of the transplant surgery. The storage procedure results in buildup of various proteins within the kidney that can injure the donated kidney after it is transplanted. One of these proteins is tumor necrosis factor-alpha (TNF-alpha).
The purpose of this study is to evaluate whether taking infliximab, which blocks tumor necrosis factor alpha (TNF-alpha), just prior to transplant surgery, along with usual transplant medicines will protect the donated kidney from damage caused by TNF-alpha and help keep the transplanted kidney healthy for a longer period of time.
详细描述
This is a Phase 2, multicenter, randomized, double blind (masked), placebo-controlled, 2-arm clinical trial of 300 deceased donor kidney transplant recipients. Participants will be randomized (1:1) to the experimental or control arm (150 subjects per arm).
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
- Triple (Participant, Care Provider, Investigator)
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 of age) male and female recipients (all races and ethnicities)
- •Subject must be able to understand and provide consent
- •Recipients of deceased donor kidney transplants (including re-transplants)
- •Negative crossmatch, actual or virtual, or a PRA of 0% on historic and current sera as determined by each participating study center
- •Donor kidneys from deceased donors and donors after cardiac death (DCD) with Kidney Donor Profile Indices (KDPI) ranging from ≥20 to <95
- •Female participants of childbearing potential must have a negative pregnancy test upon study entry
- •Subjects must have a negative test result for latent tuberculosis (TB) infection (PPD, QuantiFERON, ELISPOT):
- •Subjects who have a negative test result for latent TB infection within 1 year of transplant date are eligible for enrollment and no further action is required
- •Subjects who have a negative test for latent TB infection that is greater than 1 year old are eligible for enrollment but are required to have a repeat test prior to transplantation.
排除标准
- •Inability or unwillingness of a participant to give written informed consent or comply with study protocol
- •Recipients of living donor transplants
- •Presence of other transplanted solid organ (heart, lung, liver, pancreas, small intestines) or co-transplanted organ
- •Human immunodeficiency virus positive (HIV+) recipients
- •Epstein-Barr virus Immunoglobulin G (EBV IgG) negative recipients
- •Hepatitis B surface antigen positive kidney transplant recipients
- •Hepatitis B core antibody positive kidney transplant recipients
- •Hepatitis B negative kidney transplant recipients that receive transplants from Hepatitis B core antibody positive donor
- •Hepatitis C Virus positive (HCV+) patients who are either untreated or have failed to demonstrate sustained viral remission for more than 12 months after anti-viral treatment
- •Recipients with a previous history of active TB
- •Recipients with a positive test for latent TB infection (PPD, QuantiFERON, ELISPOT), regardless of previous therapy
- •Any severe infection at the time of transplantation.
- •-Note: Severe infection determination will be made by the local site investigator.
- •Severe congestive heart failure (NYHA functional class III or higher)
- •Subjects with a known hypersensitivity to any murine/ mouse proteins
- •Subjects with any history of receiving any anti-tumor necrosis factor (anti- TNF) products
- •Subjects in whom rabbit anti-thymocyte globulin (Thymoglobulin®) or infliximab might not be tolerated
- •Subjects with a white blood cell count less than 3000/mm^3
- •Subjects with a platelet count less than 100,000/mm^3
- •Subjects with systolic blood pressure <100 mm/Hg
- •Subjects with symptomatic orthostatic hypotension or currently requiring Midodrine for blood pressure support
- •Subjects from, or who have traveled, to endemic areas with a history of active histoplasmosis or, with a chest x-ray consistent with previous active histoplasmosis (no serological testing required) :
- •-Endemic regions determined by site based on local standard of care.
- •Subjects currently or formerly residing in regions of the United States that are highly endemic for coccidioidomycosis, and who have a positive serologic test for coccidioidomycosis:
- •-Endemic regions determined by site based on local standard of care.
- •Recipients are excluded if the local site decides to treat the recipient with fluconazole because of diagnosis or suspicion of fungal infection the donor
- •Subjects that receive IVIG treatment within 3 months of transplant or planned intravenous immunoglobulin (IVIG) treatment peri-transplant
- •Use of an investigational agent within 4-weeks prior to study entry.
研究组 & 干预措施
Experimental
rATG is co-administered with anti-TNFa (infliximab/Remicade®) plus maintenance therapy with tacrolimus, a mycophenolic acid derivative (either MMF or enteric coated MPA) and prednisone.
干预措施: Infliximab (Biological)
Experimental
rATG is co-administered with anti-TNFa (infliximab/Remicade®) plus maintenance therapy with tacrolimus, a mycophenolic acid derivative (either MMF or enteric coated MPA) and prednisone.
干预措施: Methylprednisolone (Drug)
Experimental
rATG is co-administered with anti-TNFa (infliximab/Remicade®) plus maintenance therapy with tacrolimus, a mycophenolic acid derivative (either MMF or enteric coated MPA) and prednisone.
干预措施: Mycophenolate Mofetil (Drug)
Experimental
rATG is co-administered with anti-TNFa (infliximab/Remicade®) plus maintenance therapy with tacrolimus, a mycophenolic acid derivative (either MMF or enteric coated MPA) and prednisone.
干预措施: Tacrolimus (Drug)
Experimental
rATG is co-administered with anti-TNFa (infliximab/Remicade®) plus maintenance therapy with tacrolimus, a mycophenolic acid derivative (either MMF or enteric coated MPA) and prednisone.
干预措施: Thymoglobulin® (Biological)
Experimental
rATG is co-administered with anti-TNFa (infliximab/Remicade®) plus maintenance therapy with tacrolimus, a mycophenolic acid derivative (either MMF or enteric coated MPA) and prednisone.
干预措施: Acetaminophen (Drug)
Experimental
rATG is co-administered with anti-TNFa (infliximab/Remicade®) plus maintenance therapy with tacrolimus, a mycophenolic acid derivative (either MMF or enteric coated MPA) and prednisone.
干预措施: Loratadine (Drug)
Experimental
rATG is co-administered with anti-TNFa (infliximab/Remicade®) plus maintenance therapy with tacrolimus, a mycophenolic acid derivative (either MMF or enteric coated MPA) and prednisone.
干预措施: Prednisone (Drug)
Experimental
rATG is co-administered with anti-TNFa (infliximab/Remicade®) plus maintenance therapy with tacrolimus, a mycophenolic acid derivative (either MMF or enteric coated MPA) and prednisone.
干预措施: Diphenhydramine (Drug)
Control
Rabbit anti-thymocyte globulin (rATG/Thymoglobulin®) plus placebo (Sterile normal saline) induction followed by maintenance therapy with tacrolimus, a mycophenolic acid derivative (either MMF or enteric coated MPA) and prednisone.
干预措施: Methylprednisolone (Drug)
Control
Rabbit anti-thymocyte globulin (rATG/Thymoglobulin®) plus placebo (Sterile normal saline) induction followed by maintenance therapy with tacrolimus, a mycophenolic acid derivative (either MMF or enteric coated MPA) and prednisone.
干预措施: Mycophenolate Mofetil (Drug)
Control
Rabbit anti-thymocyte globulin (rATG/Thymoglobulin®) plus placebo (Sterile normal saline) induction followed by maintenance therapy with tacrolimus, a mycophenolic acid derivative (either MMF or enteric coated MPA) and prednisone.
干预措施: Tacrolimus (Drug)
Control
Rabbit anti-thymocyte globulin (rATG/Thymoglobulin®) plus placebo (Sterile normal saline) induction followed by maintenance therapy with tacrolimus, a mycophenolic acid derivative (either MMF or enteric coated MPA) and prednisone.
干预措施: Thymoglobulin® (Biological)
Control
Rabbit anti-thymocyte globulin (rATG/Thymoglobulin®) plus placebo (Sterile normal saline) induction followed by maintenance therapy with tacrolimus, a mycophenolic acid derivative (either MMF or enteric coated MPA) and prednisone.
干预措施: Acetaminophen (Drug)
Control
Rabbit anti-thymocyte globulin (rATG/Thymoglobulin®) plus placebo (Sterile normal saline) induction followed by maintenance therapy with tacrolimus, a mycophenolic acid derivative (either MMF or enteric coated MPA) and prednisone.
干预措施: Loratadine (Drug)
Control
Rabbit anti-thymocyte globulin (rATG/Thymoglobulin®) plus placebo (Sterile normal saline) induction followed by maintenance therapy with tacrolimus, a mycophenolic acid derivative (either MMF or enteric coated MPA) and prednisone.
干预措施: Placebo for Infliximab (Biological)
Control
Rabbit anti-thymocyte globulin (rATG/Thymoglobulin®) plus placebo (Sterile normal saline) induction followed by maintenance therapy with tacrolimus, a mycophenolic acid derivative (either MMF or enteric coated MPA) and prednisone.
干预措施: Prednisone (Drug)
Control
Rabbit anti-thymocyte globulin (rATG/Thymoglobulin®) plus placebo (Sterile normal saline) induction followed by maintenance therapy with tacrolimus, a mycophenolic acid derivative (either MMF or enteric coated MPA) and prednisone.
干预措施: Diphenhydramine (Drug)
结局指标
主要结局
The Difference Between the Mean eGFR (Modified MDRD) in the Experimental vs. Control Groups.
时间窗: 24-Month post-transplantation
Glomerular filtration rate (GFR) is a measure of kidney function and helps determine the stage of kidney disease. eGFR was estimated using the Modification of Diet in Renal Disease (MDRD) equation. A value of 90+ means kidney function is normal. A value between 60 and 89 indicates mildly reduced kidney function, pointing to kidney disease. Values between 30 and 59 indicates moderately reduced kidney function. Values between 15 and 29 indicate severely reduced kidney function. Values below 15 indicate very severe or endstage kidney failure. eGFR values from months 1, 3, 6, 12, 18, and 24 were used to generate an estimate of the month 24 eGFR for each treatment group.
次要结局
- Percent of Participants With Biopsy Proven Acute Cellular Rejection (BPAR)(6 month post-transplantation)
- Percent of Participants With Biopsy Proven Acute Cellular Rejection (BPAR) or Borderline Rejection(24 months post-transplantation)
- Percent of Participants With Biopsy Proven Acute Antibody Mediated Rejection (AMR).(24 months post-transplantation)
- Change in eGFR Between 3 Months and 24 Months as Measured by MDRD(3 months and 24 months post-transplantation)
- Percent of Participants With Biopsy Proven Acute Cellular Rejection (BPAR).(24 months post-transplantation)
- BANFF Grades of First Acute Cellular Rejections (ACR).(6 month post-transplantation)
- Percent of Participants With Biopsy Proven Acute Cellular Rejection (BPAR) or Borderline Rejection.(6 months post-transplantation)
- Percent of Participants With Biopsy Proven Acute Antibody Mediated Rejection AMR or Suspicious for AMR.(24 months post-transplantation)
- Percent of Participants With BANFF Chronicity Scores > or Equal 2 on the 24 Month Biopsy.(24 months post-transplantation)
- Change in BANFF Chronicity Scores Between Implantation and the 24 Month Biopsy.(24 months post-transplantation)
- Percent of Participants With Locally Treated Rejection, Defined as Treatment Administered for Rejection Based on Clinical Signs or Biopsy Findings.(24 months post-transplantation)
- Change in eGFR Between Post-transplant Nadir and 24 Months as Measured by CKD-EPI(6 months and 24 months post-transplantation)
- Change in eGFR Between 6 Months and 24 Months as Measured by CKD-EPI(6 months and 24 months post-transplantation)
- Duration of Delayed Graft Function (DGF), Defined as Time From Transplantation to the Last Required Dialysis Treatment.(First post-transplant dialysis treatment to last post-transplant dialysis treatment)
- The Percent of Participants With a Serum Creatinine of More Than 3 mg/dL.(Day 5 post-transplantation)
- Percent of Participants With Biopsy Proven Acute Antibody Mediated Rejection (AMR)(6 months post-transplantation)
- Percent of Participants With Biopsy Proven Acute Antibody Mediated Rejection AMR or Suspicious for AMR(6 months post-transplantation)
- BANFF Grades of First AMR.(6 months post-transplantation)
- Change in eGFR Between 3 Months and 24 Months as Measured by CKD-EPI(3 months and 24 months post-transplantation)
- Change in eGFR Between Post-transplant Nadir and 24 Months as Measured by MDRD(6 months and 24 months post-transplantation)
- Change in eGFR Between 6 Months and 24 Months as Measured by MDRD(6 months and 24 months post-transplantation)
- Percent of Participants With Death or Graft Failure.(24 months post-transplantation)
- Percent of Participants With Mycobacterial or Fungal Infections(24 months post-transplantation)
- eGFR Values as Measured by MDRD(Days 30, 60, and 180 post-transplantation)
- Percent of Participants That Required at Least One Dialysis Treatment.(1 week post-transplantation)
- Number of Dialysis Sessions.(8 weeks post-transplantation)
- Percent of Participants With Primary Non-Function (PNF), Defined as Dialysis-dependency for More Than 3 Months.(Transplantation through at least month 3 up to month 24)
- The Percent of Participants Who Need Dialysis After Week 1.(1 week to 24 months post-transplantation)
- eGFR Values as Measured by CKD-EPI(Days 30, 90, and 180 post-transplantation)
- Percent of Participants With Only Graft Failure.(24 months post-transplantation)
- Days From Transplantation Until Event (ACR, AMR, or Hospitalization for Infection and/or Malignancy)(24 months post-transplantation)
- The Percent of Participants Whose Day 2 Serum CRR Was Less Than 30%.(Day 2 post-transplantation)
- Percent of Participants With de Novo DSA.(24 months post-transplantation)
- Percent of Participants With BK Viremia That Require a Change in Immunosuppression or Anti-viral Treatment as Per Standard of Care at the Site.(24 months post-transplantation)
- Creatinine Reduction Ratio (CRR), Defined as the First Creatinine on Day 2 Divided by he First Creatinine After Surgery(Day 2 post-transplantation)
- The Percent of Participants Whose Day 5 Serum CRR Was Less Than 70%.(Day 5 post-transplantation)
- Percent of Participants With Any Infection Requiring Hospitalization or Resulting in Death.(24 months post-transplantation)
- Change From Baseline (Immediately After Surgery) in Serum Creatinine.(24, 48 and 72 hours post-transplantation)
- Creatinine Reduction Ratio (CRR), Defined as the First Creatinine on Day 5 Divided by the First Creatinine After Surgery.(Day 5 post-transplantation)
- Percent of Participants With CMV Viremia That Require a Change in Immunosuppression or Anti-viral Treatment as Per Standard of Care at the Site(24 months post-transplantation)
- Percent of Participants With Malignancy.(24 months post-transplantation)
- Percent of Participants With Impaired Wound Healing Manifested by Wound Dehiscence, Wound Infection, or Hernia at the Site of the Transplant Incision(24 months post-transplantation)