Urine CXCL10 Monitoring Trial in Kidney Transplant

NCT ID: NCT03206801

Last Updated: 2025-03-25

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE2/PHASE3

Total Enrollment

420 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-04-03

Study Completion Date

2025-09-26

Brief Summary

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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

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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.

Conditions

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Kidney Transplant; Complications Rejection of Renal Transplant

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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).
Primary Study Purpose

SCREENING

Blinding Strategy

SINGLE

Outcome Assessors
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.

Study Groups

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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.

Group Type EXPERIMENTAL

Kidney transplant biopsy

Intervention Type PROCEDURE

Elevated urine CXCL10 will trigger a study biopsy in patients randomized to the intervention arm. Subclinical rejection will be treated per protocol.

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.

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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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.

Intervention Type PROCEDURE

Other Intervention Names

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Protocol biopsy

Eligibility Criteria

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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.

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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Canadian Institutes of Health Research (CIHR)

OTHER_GOV

Sponsor Role collaborator

Canadian National Transplant Research Program

OTHER

Sponsor Role collaborator

University of Manitoba

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Julie Ho, MD

Role: PRINCIPAL_INVESTIGATOR

University of Manitoba

Locations

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Royal Adelaide Hospital

Adelaide, South Australia, Australia

Site Status

University of Calgary

Calgary, Alberta, Canada

Site Status

University of Manitoba, Transplant Manitoba Adult Kidney Program

Winnipeg, Manitoba, Canada

Site Status

Western University

London, Ontario, Canada

Site Status

University of Ottawa

Ottawa, Ontario, Canada

Site Status

University Health Network, University of Toronto

Toronto, Ontario, Canada

Site Status

Centre de recherche du CHUM (CRCHUM)

Montreal, Quebec, Canada

Site Status

McGill

Montreal, Quebec, Canada

Site Status

Université Laval

Québec, Quebec, Canada

Site Status

Countries

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Australia Canada

References

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Ho J, Rush DN, Karpinski M, Storsley L, Gibson IW, Bestland J, Gao A, Stefura W, HayGlass KT, Nickerson PW. Validation of urinary CXCL10 as a marker of borderline, subclinical, and clinical tubulitis. Transplantation. 2011 Oct 27;92(8):878-82. doi: 10.1097/TP.0b013e31822d4de1.

Reference Type BACKGROUND
PMID: 21876477 (View on PubMed)

Hirt-Minkowski P, Amico P, Ho J, Gao A, Bestland J, Hopfer H, Steiger J, Dickenmann M, Burkhalter F, Rush D, Nickerson P, Schaub S. Detection of clinical and subclinical tubulo-interstitial inflammation by the urinary CXCL10 chemokine in a real-life setting. Am J Transplant. 2012 Jul;12(7):1811-23. doi: 10.1111/j.1600-6143.2012.03999.x. Epub 2012 Mar 5.

Reference Type BACKGROUND
PMID: 22390571 (View on PubMed)

Blydt-Hansen TD, Gibson IW, Gao A, Dufault B, Ho J. Elevated urinary CXCL10-to-creatinine ratio is associated with subclinical and clinical rejection in pediatric renal transplantation. Transplantation. 2015 Apr;99(4):797-804. doi: 10.1097/TP.0000000000000419.

Reference Type BACKGROUND
PMID: 25222013 (View on PubMed)

Hirt-Minkowski P, Ho J, Gao A, Amico P, Koller MT, Hopfer H, Rush DN, Nickerson PW, Schaub S. Prediction of Long-term Renal Allograft Outcome By Early Urinary CXCL10 Chemokine Levels. Transplant Direct. 2015 Sep 24;1(8):e31. doi: 10.1097/TXD.0000000000000537. eCollection 2015 Sep.

Reference Type BACKGROUND
PMID: 27500231 (View on PubMed)

Hirt-Minkowski P, Rush DN, Gao A, Hopfer H, Wiebe C, Nickerson PW, Schaub S, Ho J. Six-Month Urinary CCL2 and CXCL10 Levels Predict Long-term Renal Allograft Outcome. Transplantation. 2016 Sep;100(9):1988-96. doi: 10.1097/TP.0000000000001304.

Reference Type BACKGROUND
PMID: 27548845 (View on PubMed)

Ho J, Sharma A, Mandal R, Wishart DS, Wiebe C, Storsley L, Karpinski M, Gibson IW, Nickerson PW, Rush DN. Detecting Renal Allograft Inflammation Using Quantitative Urine Metabolomics and CXCL10. Transplant Direct. 2016 May 19;2(6):e78. doi: 10.1097/TXD.0000000000000589. eCollection 2016 Jun.

Reference Type BACKGROUND
PMID: 27500268 (View on PubMed)

Ho J, Rush DN, Krokhin O, Antonovici M, Gao A, Bestland J, Wiebe C, Hiebert B, Rigatto C, Gibson IW, Wilkins JA, Nickerson PW. Elevated Urinary Matrix Metalloproteinase-7 Detects Underlying Renal Allograft Inflammation and Injury. Transplantation. 2016 Mar;100(3):648-54. doi: 10.1097/TP.0000000000000867.

Reference Type BACKGROUND
PMID: 26906940 (View on PubMed)

Hricik DE, Nickerson P, Formica RN, Poggio ED, Rush D, Newell KA, Goebel J, Gibson IW, Fairchild RL, Riggs M, Spain K, Ikle D, Bridges ND, Heeger PS; CTOT-01 consortium. Multicenter validation of urinary CXCL9 as a risk-stratifying biomarker for kidney transplant injury. Am J Transplant. 2013 Oct;13(10):2634-44. doi: 10.1111/ajt.12426. Epub 2013 Aug 22.

Reference Type BACKGROUND
PMID: 23968332 (View on PubMed)

Rabant M, Amrouche L, Lebreton X, Aulagnon F, Benon A, Sauvaget V, Bonifay R, Morin L, Scemla A, Delville M, Martinez F, Timsit MO, Duong Van Huyen JP, Legendre C, Terzi F, Anglicheau D. Urinary C-X-C Motif Chemokine 10 Independently Improves the Noninvasive Diagnosis of Antibody-Mediated Kidney Allograft Rejection. J Am Soc Nephrol. 2015 Nov;26(11):2840-51. doi: 10.1681/ASN.2014080797. Epub 2015 May 6.

Reference Type BACKGROUND
PMID: 25948873 (View on PubMed)

Ho J, Sharma A, Kroeker K, Carroll R, De Serres S, Gibson IW, Hirt-Minkowski P, Jevnikar A, Kim SJ, Knoll G, Rush DN, Wiebe C, Nickerson P. Multicentre randomised controlled trial protocol of urine CXCL10 monitoring strategy in kidney transplant recipients. BMJ Open. 2019 Apr 11;9(4):e024908. doi: 10.1136/bmjopen-2018-024908.

Reference Type DERIVED
PMID: 30975673 (View on PubMed)

Other Identifiers

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364003

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

TMCT-04

Identifier Type: OTHER

Identifier Source: secondary_id

B2017:076

Identifier Type: -

Identifier Source: org_study_id

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