Urine CXCL10 Monitoring Trial in Kidney Transplant

NCT03206801 | Completed Phase 2 DMC

• 3 other identifiers: B2017:076364003TMCT-04
• Study Type: interventional
• Target: 260
• Locations: 2 countries
• Sites: 9

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.

Conditions

Kidney Transplant; Complications; Rejection of Renal Transplant

Keywords

Urine biomarker; CXCL10 chemokine; Post-transplant monitoring; Protocol biopsy

Outcome Measures

Primary Outcomes (5)

• 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 Outcomes (8)

• Renal allograft function

  6, 12, 24 and 60 months post-transplant

• 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

• Albuminuria >300mg/day

  6, 12, 24 and 60 months post-transplant

Study Arms (2)

Intervention

EXPERIMENTAL

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

Control

NO INTERVENTION

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.

Interventions

Kidney transplant biopsy PROCEDURE

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

Also known as: Protocol biopsy

Intervention

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Manitoba: lead
• Canadian Institutes of Health Research (CIHR): collaborator
• Canadian National Transplant Research Program: collaborator

Study Sites (9)

Royal Adelaide Hospital

Adelaide, South Australia, 5000, Australia

Location

University of Calgary

Calgary, Alberta, Canada

Location

University of Manitoba, Transplant Manitoba Adult Kidney Program

Winnipeg, Manitoba, R3A 1R9, Canada

Location

Western University

London, Ontario, Canada

Location

University of Ottawa

Ottawa, Ontario, Canada

Location

University Health Network, University of Toronto

Toronto, Ontario, Canada

Location

Centre de recherche du CHUM (CRCHUM)

Montreal, Quebec, Canada

Location

McGill

Montreal, Quebec, Canada

Location

Université Laval

Québec, Quebec, Canada

Location

Related Publications (10)

• 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.

  PMID: 21876477 RESULT

• 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.

  PMID: 22390571 RESULT

• 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.

  PMID: 25222013 RESULT

• 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.

  PMID: 27500231 RESULT

• 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.

  PMID: 27548845 RESULT

• 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.

  PMID: 27500268 RESULT

• 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.

  PMID: 26906940 RESULT

• 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.

  PMID: 23968332 RESULT

• 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.

  PMID: 25948873 RESULT

• 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.

  PMID: 30975673 DERIVED

Study Officials

• Julie Ho, MD

  University of Manitoba

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: SCREENING
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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).

Study Record Dates

• First Submitted: June 28, 2017
• First Posted: July 2, 2017
• Study Start: April 3, 2018
• Primary Completion: June 6, 2025
• Study Completion: September 26, 2025
• Last Updated: May 5, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

CA (8); AU (1)