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Trial record 13 of 315 for:    Recruiting, Not yet recruiting, Available Studies | kidney transplantation

Urine CXCL10 Monitoring Trial in Kidney Transplant

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ClinicalTrials.gov Identifier: NCT03206801
Recruitment Status : Recruiting
First Posted : July 2, 2017
Last Update Posted : May 9, 2018
Sponsor:
Collaborators:
Canadian Institutes of Health Research (CIHR)
Canadian National Transplant Research Program
Information provided by (Responsible Party):
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.


Condition or disease Intervention/treatment Phase
Kidney Transplant; Complications Rejection of Renal Transplant Procedure: Kidney transplant biopsy Phase 2 Phase 3

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  (Clinical Trial)
Estimated Enrollment : 420 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: 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).
Masking: Single (Outcomes Assessor)
Masking Description: 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.
Primary Purpose: Screening
Official Title: A Randomized Controlled Trial of Urine CXCL10 Chemokine Monitoring Post-renal Transplant
Actual Study Start Date : April 3, 2018
Estimated Primary Completion Date : July 2021
Estimated Study Completion Date : July 2022

Resource links provided by the National Library of Medicine


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 Name: 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.



Primary Outcome Measures :
  1. Death-censored graft loss [ Time Frame: 2 weeks-12 months post-transplant ]
    Return to dialysis or re-transplant

  2. Clinical indication biopsy-proven acute rejection [ Time Frame: 2 weeks-12 months post-transplant ]
    Clinical rejection, Banff criteria

  3. De novo donor specific antibody development [ Time Frame: 2 weeks-12 months post-transplant ]
    De novo human leukocyte antibody (HLA) antibodies, donor specific

  4. Subclinical tubulitis [ Time Frame: 12-month study exit biopsy ]
    Subclinical rejection, Banff criteria

  5. Interstitial fibrosis and inflammation (IFTA + i) [ Time Frame: 12-month study exit biopsy ]
    IFTA + i, defined by Mayo criteria


Secondary Outcome Measures :
  1. Renal allograft function [ Time Frame: 6, 12, 24 and 60 months post-transplant ]
    Change in eGFR (slope, ∆) and graft function (eGFR) (absolute, mL/min)

  2. Microvascular inflammation [ Time Frame: 12-month study exit biopsy ]
    Banff ptc, g, c4d, cg

  3. Development IFTA from implantation to 12-months [ Time Frame: 12-month study exit biopsy ]
    Banff ∆ ci, ct, cv

  4. Days from transplantation to clinical-biopsy proven rejection [ Time Frame: 2 weeks-12 months post-transplant ]
    Time to biopsy proven rejection

  5. Albuminuria >300mg/day [ Time Frame: 6, 12, 24 and 60 months post-transplant ]
    Urine albumin: Cr ratio

  6. Cost-effectiveness of urine CXCL10 monitoring strategy [ Time Frame: 2 weeks-12 months post-transplant ]
    Costs of urine CXCL10 screening

  7. Quality of life [ Time Frame: 6 and 12 months post-transplant ]
    EuroQOL (EQ-5DL)

  8. Urine CXCL10 kinetics [ Time Frame: 2 weeks-12 months post-transplant ]
    Change in urine CXCL10 levels in response to rejection therapy



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 menses.

Exclusion Criteria:

  1. Primary non-function
  2. Blood group (ABO) incompatible
  3. Pre-transplant donor specific antibody (DSA) positive
  4. Human leukocyte (HLA) 0 HLA antigen D-related (DR) and 0 major HLA class 2 (DQ) mis-match
  5. Presence of other transplanted organ or co-transplanted organ
  6. Active infection at the time of randomization
  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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03206801


Contacts
Contact: Brendon Foot, BA, CCRP 204-770-7154 bfoot@wrha.mb.ca
Contact: Kiran Sran, MSc 204-787-3618 ksran2@exchange.hsc.mb.ca

Locations
Australia, South Australia
Royal Adelaide Hospital Recruiting
Adelaide, South Australia, Australia, 5000
Contact: Bronwyn Hockley    61 8 7074 3077    bronwyn.hockley@sa.gov.au   
Contact: Meg Hockley    61 8 7074 5780    meg.hockley@sa.gov.au   
Principal Investigator: Robert Carroll, MD         
Canada, Manitoba
University of Manitoba, Transplant Manitoba Adult Kidney Program Recruiting
Winnipeg, Manitoba, Canada, R3A 1R9
Contact: Michelle Lesyk, RN, BN    204-787-8590    mlesyk@hsc.mb.ca   
Contact: Kiran Sran, MSc    204-787-3618    ksran2@hsc.mb.ca   
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         
Canada, Quebec
Université Laval Recruiting
Québec City, Quebec, Canada
Contact: France Samson    418-525-4444 ext 15195    france.samson@chuq.qc.ca   
Contact: Danielle Villeneuve    418-525-4444 ext 16487    danielle.villeneuve@mail.chuq.qc.ca   
Principal Investigator: Sacha De Serres, MD         
Sponsors and Collaborators
University of Manitoba
Canadian Institutes of Health Research (CIHR)
Canadian National Transplant Research Program
Investigators
Principal Investigator: Julie Ho, MD University of Manitoba

Publications of Results:

Responsible Party: University of Manitoba
ClinicalTrials.gov Identifier: NCT03206801     History of Changes
Other Study ID Numbers: B2017:076
364003 ( Other Grant/Funding Number: Canadian Institutes of Health Research )
TMCT-04 ( Other Identifier: Transplant Manitoba )
First Posted: July 2, 2017    Key Record Dates
Last Update Posted: May 9, 2018
Last Verified: June 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by University of Manitoba:
Urine biomarker
CXCL10 chemokine
Post-transplant monitoring
Protocol biopsy