A Randomized Pilot Study of Treatment for Subclinical Antibody-Mediated Rejection in Kidney Transplant Recipients
试验速览
- 阶段
- 早期 1 期
- 状态
- 终止
- 入组人数
- 4
- 试验地点
- 1
- 主要终点
- Change in Acute Inflammatory Histologic Parameters
研究概览
简要总结
This is a pilot study to determine if extended release Envarsus at an optimal level is just as effective as more invasive standard therapies for subclinical (mild) AMR (antibody mediated rejection) in kidney transplant patients. Subjects will be randomized to either conversion to Envarsus XR (extended release); or, to a standard of care regimen of plasma exchange/IVIG (intravenous immunoglobulin)/rituximab treatments.
详细描述
There is currently minimal data to guide treatment of mild graft damage in kidney transplant patients. Some of the current therapies used often come with dangerous complications (infections, malignancies, etc.). This is a pilot study to determine if extended release Envarsus at an optimal level is just as effective as more invasive standard therapies for subclinical (mild) AMR (antibody mediated rejection) in kidney transplant patients. The subjects will be randomized to either conversion from their current tacrolimus regimen to Envarsus XR (a once a day, extended release version of tacrolimus); or, to a regimen of 5 plasma exchanges/IVIG (intravenous immunoglobulin) treatments and one treatment with rituximab. Subjects who are within their first year of transplant will visit their doctor monthly for regular tests and checks and then will have a kidney biopsy at 6 months. Subjects who had their transplant over a year prior will see the doctor for tests and checks at 1, 3 and 5 months and then will have a biopsy of the kidney at month 6.
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 79 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult (18+ years) recipients of kidney or kidney/pancreas transplants
- •Willing to sign an IRB (institutional review board)-approved consent and to comply with study requirements
- •DSA (donor specific antibodies) detected by SAB (single antigen beads) screening with MFI ≥ 2000
- •Graft biopsy performed within prior 30 days
- •Stable renal function defined by serum creatinine increase ≤ 30% over prior 6 months
- •Subacute antibody-mediated rejection on biopsy defined by ptc + g + C4d ≥ 2 by Banff 2013 criteria
排除标准
- •Kidney/liver or kidney/heart recipient
- •Unwilling/unable to undergo screening biopsy
- •HIV (human immunodeficiency virus), HCV (hepatitis-C virus), or HBsAg (hepatitis-B surface antigen) positive
- •Active/untreated infection
- •Acute cellular rejection with Banff grade 1b, 2a, 2b on initial biopsy requiring rATG (rabbit anti-thymocyte globulin) therapy
- •Pregnant or nursing females
研究组 & 干预措施
Arm 1 - conversion to Envarsus XR
Optimize: conversion to Envarsus XR (Tacrolimus Extended Release Oral Tablet [Envarsus]) with goal trough tac level > 8 ng/ml, MPA at 720 mg bid unless medically contraindicated, prednisone at current dose (5mg) or continue taper to 5mg per center standard of care protocol
干预措施: Tacrolimus Extended Release Oral Tablet [Envarsus] (Drug)
Arm 2 - plasma exchange and IVIG
Treat clinical AMR: Plasma exchange x 5 treatments, each followed by IVIG 200 mg/kg except last dose of 1 gm/kg. Rituximab 375 mg/m2 following final plasma exchange treatment.
干预措施: Plasma Exchange and IVIG (Intravenous Immunoglobulin ) (Other)
结局指标
主要结局
Change in Acute Inflammatory Histologic Parameters
时间窗: Baseline and 6 months
Any increase or reduction in ptc+g+C4d score by Banff 2013 criteria) from baseline (pre-treatment) to 6 month (post-treatment initiation). Analysis will comprise exact chi-squared tests for comparison of binomial proportions of histological response between the two treatment groups.
次要结局
- Change in MDRD GFR (Modification of Diet in Renal Disease Glomerular Filtration Rate)(6 and 12 months)
- Change in Donor-Specific Antibody (DSA) Mean Fluorescence Intensity (MFI) Level(6 and 12 months)
- Change in serum creatinine(6 and 12 months)
- Graft Survival(6 and 12 months)
- Patient Survival(6 and 12 months)
- Evaluation of Adverse Events(6 and 12 months)