Urine CXCL10 Monitoring Trial in Kidney Transplant

Phase 2

Active, not recruiting

• Conditions: Kidney Transplant; Complications; Rejection of Renal Transplant
• Interventions: Procedure: Kidney transplant biopsy

• Registration Number: NCT03206801
• Lead Sponsor: University of Manitoba

Brief Summary

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.

Detailed Description

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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2017-06-28
• Study First Submitted QC: 2017-06-29
• Study First Posted: 2017-07-02
• Study Start: 2018-04-03
• Status Verified: 2023-12
• Primary Completion: 2024-06-06
• Last Update Submitted: 2024-12-04
• Last Update Posted: 2024-12-09
• Study Completion: 2025-09-26

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 420

Inclusion Criteria

1. Participants must be able to understand and provide written informed consent
2. Stated willingness to comply with all study procedures and availability for the duration of the study
3. All ethnic and gender groups will have equal access to the study
4. Incident adult (age ≥18) renal transplant patients with a living or deceased donor kidney transplant
5. Confirmed elevated urine CXCL10:Cr without a urinary tract infection or gross hematuria.

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Exclusion Criteria

1. Primary non-function
2. Blood group (ABO) incompatible
3. Pre-transplant donor specific antibody (DSA) positive (MFI>1000 OR positive flow crossmatch)
4. Human leukocyte (HLA) 0 HLA antigen D-related (DR) + 0 major HLA class 2 (DQ) mismatch
5. Presence of other transplanted organ or co-transplanted organ
6. Medical contraindication to biopsy or rejection treatment
7. Followed outside of investigational center
8. Participation in other interventional trials within 4-weeks post-transplant or anytime post-transplant till study end at 12-months
9. Intention to not use a maintenance immunosuppression regimen consisting of calcineurin inhibitor (CNI) and anti-proliferative agents
10. 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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Intervention	Kidney transplant biopsy	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.

Primary Outcome Measures

Name	Time	Method
Subclinical tubulitis	12-month study exit biopsy	Subclinical rejection, Banff criteria
De novo donor specific antibody development	2 weeks-12 months post-transplant	De novo human leukocyte antibody (HLA) antibodies, donor specific
Interstitial fibrosis and inflammation (IFTA + i)	12-month study exit biopsy	IFTA + i, defined by Mayo criteria
Death-censored graft loss	2 weeks-12 months post-transplant	Return to dialysis or re-transplant
Clinical indication biopsy-proven acute rejection	2 weeks-12 months post-transplant	Clinical rejection, Banff criteria

Secondary Outcome Measures

Name	Time	Method
Microvascular inflammation	12-month study exit biopsy	Banff ptc, g, c4d, cg
Development IFTA from implantation to 12-months	12-month study exit biopsy	Banff ∆ ci, ct, cv
Days from transplantation to clinical-biopsy proven rejection	2 weeks-12 months post-transplant	Time to biopsy proven rejection
Quality of life	6 and 12 months post-transplant	EuroQOL (EQ-5DL)
Renal allograft function	6, 12, 24 and 60 months post-transplant	Change in eGFR (slope, ∆) and graft function (eGFR) (absolute, mL/min)
Albuminuria >300mg/day	6, 12, 24 and 60 months post-transplant	Urine albumin: Cr ratio
Cost-effectiveness of urine CXCL10 monitoring strategy	2 weeks-12 months post-transplant	Costs of urine CXCL10 screening
Urine CXCL10 kinetics	2 weeks-12 months post-transplant	Change in urine CXCL10 levels in response to rejection therapy

Trial Locations

Locations (9)

University Health Network, University of Toronto; 🇨🇦 Toronto, Ontario, Canada

Royal Adelaide Hospital; 🇦🇺 Adelaide, South Australia, Australia

University of Calgary; 🇨🇦 Calgary, Alberta, Canada

University of Manitoba, Transplant Manitoba Adult Kidney Program; 🇨🇦 Winnipeg, Manitoba, Canada

Western University; 🇨🇦 London, Ontario, Canada

University of Ottawa; 🇨🇦 Ottawa, Ontario, Canada

McGill; 🇨🇦 Montreal, Quebec, Canada

Centre de recherche du CHUM (CRCHUM); 🇨🇦 Montréal, Quebec, Canada

Université Laval; 🇨🇦 Québec City, Quebec, Canada