A Randomized Controlled Trial of Urine CXCL10 Chemokine Monitoring Post-renal Transplant
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 420
- 试验地点
- 13
- 主要终点
- Subclinical tubulitis
研究概览
简要总结
This is a Phase II-III multi-center prospective randomized controlled clinical trial of incident adult renal transplant patients.
The primary objective of this study is to determine if the early treatment of rejection, as detected by urinary CXCL10, will improve renal allograft outcomes.
详细描述
This is a Phase II-III multi-center prospective randomized controlled clinical trial of incident adult renal transplant patients. Patients will be screened for eligibility (n≈485) and n≈420 will be enrolled and undergo post-transplant surveillance with urinary CXCL10. Two hundred and fifty patients deemed at high risk for rejection based on a confirmed elevated urine CXCL10 will undergo 1:1 randomization to the intervention and control arms, stratified by center. The total study duration is approximately 5 years; and there two main phases - screening and intervention.
All eligible, enrolled patients will undergo the Screening Phase (n≈420). Routine urine CXCL10 screening will be done from 2 weeks - 9 months post-transplant. We have previously shown that urine CXCL10 is elevated in ischemia-reperfusion injury, so screening will commence at 2 weeks (+/- 4 days) to exclude this as a potential confounding factor (60).
If patient develops a confirmed elevated urine CXCL10 level and is considered high risk for rejection, they will proceed to Randomization in the Intervention Phase, which can occur anytime between 2 weeks - 9 months post-transplant. Participants in the Intervention Arm will undergo renal biopsy to check for rejection. Biopsy-proven subclinical rejection will be treated per study protocol. Participants in the Control Arm will continue routine post-transplant surveillance with serum creatinine and proteinuria; serial urine samples will continue to be collected and analyzed (blinded), but not used to direct care. All randomized participants will undergo a 12-month study exit visit with protocol biopsy to determine primary, secondary and long-term outcomes.
Enrolled patients with persistently low urine CXCL10 and low risk of rejection from 2 weeks - 9 months post-transplant will be considered Off-Study (not randomized). They will undergo a 12-month study exit visit (+/- 7 days) to determine secondary and long-term outcomes.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Screening
- 盲法
- Single (Outcomes Assessor)
盲法说明
The assessor of the primary outcome will be masked. As the intervention involves a study biopsy, based on an elevated urine CXCL10, it is not possible to blind the participant, care provider or 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
- •Participants must be able to understand and provide written informed consent
- •Stated willingness to comply with all study procedures and availability for the duration of the study
- •All ethnic and gender groups will have equal access to the study
- •Incident adult (age ≥18) renal transplant patients with a living or deceased donor kidney transplant
- •Confirmed elevated urine CXCL10:Cr without a urinary tract infection or gross hematuria.
排除标准
- •Primary non-function
- •Blood group (ABO) incompatible
- •Pre-transplant donor specific antibody (DSA) positive (MFI>1000 OR positive flow crossmatch)
- •Human leukocyte (HLA) 0 HLA antigen D-related (DR) + 0 major HLA class 2 (DQ) mismatch
- •Presence of other transplanted organ or co-transplanted organ
- •Medical contraindication to biopsy or rejection treatment
- •Followed outside of investigational center
- •Participation in other interventional trials within 4-weeks post-transplant or anytime post-transplant till study end at 12-months
- •Intention to not use a maintenance immunosuppression regimen consisting of calcineurin inhibitor (CNI) and anti-proliferative agents
- •Any condition that, in the opinion of the investigator, would pose risk to the subject's safe participation, or interfere with their ability to comply with the study requirements, or may impact the quality of interpretation of the data.
结局指标
主要结局
Subclinical tubulitis
时间窗: 12-month study exit biopsy
Subclinical rejection, Banff criteria
De novo donor specific antibody development
时间窗: 2 weeks-12 months post-transplant
De novo human leukocyte antibody (HLA) antibodies, donor specific
Interstitial fibrosis and inflammation (IFTA + i)
时间窗: 12-month study exit biopsy
IFTA + i, defined by Mayo criteria
Death-censored graft loss
时间窗: 2 weeks-12 months post-transplant
Return to dialysis or re-transplant
Clinical indication biopsy-proven acute rejection
时间窗: 2 weeks-12 months post-transplant
Clinical rejection, Banff criteria
次要结局
- Microvascular inflammation(12-month study exit biopsy)
- Development IFTA from implantation to 12-months(12-month study exit biopsy)
- Days from transplantation to clinical-biopsy proven rejection(2 weeks-12 months post-transplant)
- Quality of life(6 and 12 months post-transplant)
- Renal allograft function(6, 12, 24 and 60 months post-transplant)
- Albuminuria >300mg/day(6, 12, 24 and 60 months post-transplant)
- Cost-effectiveness of urine CXCL10 monitoring strategy(2 weeks-12 months post-transplant)
- Urine CXCL10 kinetics(2 weeks-12 months post-transplant)