Urine CXCL10 Monitoring Trial in Kidney Transplant
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|ClinicalTrials.gov Identifier: NCT03206801|
Recruitment Status : Recruiting
First Posted : July 2, 2017
Last Update Posted : May 9, 2018
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.
|Condition or disease||Intervention/treatment||Phase|
|Kidney Transplant; Complications Rejection of Renal Transplant||Procedure: Kidney transplant biopsy||Phase 2 Phase 3|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||420 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||This is a Phase II-III multi-center prospective randomized controlled clinical trial of incident adult renal transplant patients. Patients with elevated urine CXCL10 will be randomized 1:1 to the intervention and control arms, stratified by center (~ 420 enrolled to urine CXCL10 screening for n=250 randomized participants).|
|Masking:||Single (Outcomes Assessor)|
|Masking Description:||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.|
|Official Title:||A Randomized Controlled Trial of Urine CXCL10 Chemokine Monitoring Post-renal Transplant|
|Actual Study Start Date :||April 3, 2018|
|Estimated Primary Completion Date :||July 2021|
|Estimated Study Completion Date :||July 2022|
Participants with high urine CXCL10 randomized to the Intervention Arm will undergo a kidney transplant biopsy to check for rejection. Biopsy-proven subclinical rejection will be treated per study protocol.
Procedure: Kidney transplant biopsy
Elevated urine CXCL10 will trigger a study biopsy in patients randomized to the intervention arm. Subclinical rejection will be treated per protocol.
Other Name: Protocol biopsy
No Intervention: Control
Participants with high urine CXCL10 randomized to 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.
- Death-censored graft loss [ Time Frame: 2 weeks-12 months post-transplant ]Return to dialysis or re-transplant
- Clinical indication biopsy-proven acute rejection [ Time Frame: 2 weeks-12 months post-transplant ]Clinical rejection, Banff criteria
- De novo donor specific antibody development [ Time Frame: 2 weeks-12 months post-transplant ]De novo human leukocyte antibody (HLA) antibodies, donor specific
- Subclinical tubulitis [ Time Frame: 12-month study exit biopsy ]Subclinical rejection, Banff criteria
- Interstitial fibrosis and inflammation (IFTA + i) [ Time Frame: 12-month study exit biopsy ]IFTA + i, defined by Mayo criteria
- Renal allograft function [ Time Frame: 6, 12, 24 and 60 months post-transplant ]Change in eGFR (slope, ∆) and graft function (eGFR) (absolute, mL/min)
- Microvascular inflammation [ Time Frame: 12-month study exit biopsy ]Banff ptc, g, c4d, cg
- Development IFTA from implantation to 12-months [ Time Frame: 12-month study exit biopsy ]Banff ∆ ci, ct, cv
- Days from transplantation to clinical-biopsy proven rejection [ Time Frame: 2 weeks-12 months post-transplant ]Time to biopsy proven rejection
- Albuminuria >300mg/day [ Time Frame: 6, 12, 24 and 60 months post-transplant ]Urine albumin: Cr ratio
- Cost-effectiveness of urine CXCL10 monitoring strategy [ Time Frame: 2 weeks-12 months post-transplant ]Costs of urine CXCL10 screening
- Quality of life [ Time Frame: 6 and 12 months post-transplant ]EuroQOL (EQ-5DL)
- Urine CXCL10 kinetics [ Time Frame: 2 weeks-12 months post-transplant ]Change in urine CXCL10 levels in response to rejection therapy
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03206801
|Contact: Brendon Foot, BA, CCRPfirstname.lastname@example.org|
|Contact: Kiran Sran, MScemail@example.com|
|Australia, South Australia|
|Royal Adelaide Hospital||Recruiting|
|Adelaide, South Australia, Australia, 5000|
|Contact: Bronwyn Hockley 61 8 7074 3077 firstname.lastname@example.org|
|Contact: Meg Hockley 61 8 7074 5780 email@example.com|
|Principal Investigator: Robert Carroll, MD|
|University of Manitoba, Transplant Manitoba Adult Kidney Program||Recruiting|
|Winnipeg, Manitoba, Canada, R3A 1R9|
|Contact: Michelle Lesyk, RN, BN 204-787-8590 firstname.lastname@example.org|
|Contact: Kiran Sran, MSc 204-787-3618 email@example.com|
|Principal Investigator: Julie Ho, MD|
|Sub-Investigator: Peter Nickerson, MD|
|Sub-Investigator: David Rush, MD|
|Sub-Investigator: Chris Wiebe, MD|
|Sub-Investigator: Ian Gibson, MD|
|Québec City, Quebec, Canada|
|Contact: France Samson 418-525-4444 ext 15195 firstname.lastname@example.org|
|Contact: Danielle Villeneuve 418-525-4444 ext 16487 email@example.com|
|Principal Investigator: Sacha De Serres, MD|
|Principal Investigator:||Julie Ho, MD||University of Manitoba|