Urine CXCL10 Monitoring Trial in Kidney Transplant

November 30, 2023 updated by: University of Manitoba

A Randomized Controlled Trial of Urine CXCL10 Chemokine Monitoring Post-renal Transplant

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

420

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

  • Name: Michelle Lesyk, RN, BN
  • Phone Number: 204-787-8590
  • Email: mlesyk@hsc.mb.ca

Study Locations

  • Australia
    • South Australia
      • Adelaide, South Australia, Australia, 5000
        • Recruiting
        • Royal Adelaide Hospital
        • Contact:
        • Contact:
        • Principal Investigator:
          • Robert Carroll, MD
  • Canada
    • Alberta
    • Manitoba
      • Winnipeg, Manitoba, Canada, R3A 1R9
        • Recruiting
        • University of Manitoba, Transplant Manitoba Adult Kidney Program
        • Contact:
        • Contact:
        • 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
    • Ontario
      • London, Ontario, Canada
        • Recruiting
        • Western University
        • Principal Investigator:
          • Lakshman Gunaratnam, MD
        • Contact:
      • Ottawa, Ontario, Canada
        • Terminated
        • University of Ottawa
    • Quebec

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

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?

Design Details

  • Primary Purpose: Screening
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

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.
Other Names:
  • 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.

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Manitoba

Collaborators

Canadian Institutes of Health Research (CIHR)
Canadian National Transplant Research Program

Investigators

  • Principal Investigator: Julie Ho, MD, University of Manitoba

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 3, 2018

Primary Completion (Estimated)

December 31, 2024

Study Completion (Estimated)

December 31, 2025

Study Registration Dates

First Submitted

June 28, 2017

First Submitted That Met QC Criteria

June 29, 2017

First Posted (Actual)

July 2, 2017

Study Record Updates

Last Update Posted (Actual)

December 1, 2023

Last Update Submitted That Met QC Criteria

November 30, 2023

Last Verified

December 1, 2023

More Information

Terms related to this study

Keywords

Other Study ID Numbers

  • B2017:076
  • 364003 (Other Grant/Funding Number: Canadian Institutes of Health Research)
  • TMCT-04 (Other Identifier: Transplant Manitoba)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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