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Urine CXCL10 Monitoring Trial in Kidney Transplant

PHASE2PHASE3RECRUITING

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.

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Study details:

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.

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Eligibility criteria

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Inclusion criteria

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.

Exclusion criteria

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.

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Eligibility

Age eligible for study : 18 and older

Healthy volunteers accepted : No

Gender eligible for study: All

Things to know

Study dates

Study start: 2018-04-03

Primary completion: 2024-12-31

Study completion finish: 2025-12-31

Study type

SCREENING

Phase

PHASE2

PHASE3

Trial ID

NCT03206801

Intervention or treatment

PROCEDURE: Kidney transplant biopsy

Conditions

• Kidney Transplant; Complications
• Rejection of Renal Transplant

Image related to Kidney Transplant; Complications

Condition: Kidney Transplant; Complications, Rejection of Renal Transplant
PROCEDURE: Kidney transplant biopsy
Adelaide, South Australia, Australia
Sponsor: University of Manitoba

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Find a site

Closest Location:

Royal Adelaide Hospital

Research sites nearby

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Royal Adelaide Hospital
Adelaide, South Australia, Australia

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Intervention 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.
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.	Not specified

What is the study measuring?

Primary outcome

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

Secondary outcome

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

Frequently Asked Questions

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References

Clinical Trials Gov: Urine CXCL10 Monitoring Trial in Kidney Transplant