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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

Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.

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

    Study type

    SCREENING

    phase

    Phase

      PHASE2

      PHASE3

    trial

    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

    Find a site

    Closest Location:

    Royal Adelaide Hospital

    Research sites nearby

    Select from list below to view details:

    • Royal Adelaide Hospital

      Adelaide, South Australia, Australia

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    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/ArmIntervention/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 MeasurePrimary Outcome DescriptionPrimary Outcome Time Frame
    Death-censored graft lossReturn to dialysis or re-transplant2 weeks-12 months post-transplant
    Clinical indication biopsy-proven acute rejectionClinical rejection, Banff criteria2 weeks-12 months post-transplant
    De novo donor specific antibody developmentDe novo human leukocyte antibody (HLA) antibodies, donor specific2 weeks-12 months post-transplant
    Subclinical tubulitisSubclinical rejection, Banff criteria12-month study exit biopsy
    Interstitial fibrosis and inflammation (IFTA + i)IFTA + i, defined by Mayo criteria12-month study exit biopsy

    Secondary outcome

    Secondary Outcome MeasureSecondary Outcome DescriptionSecondary Outcome Time Frame
    Renal allograft functionChange in eGFR (slope, ∆) and graft function (eGFR) (absolute, mL/min)6, 12, 24 and 60 months post-transplant
    Microvascular inflammationBanff ptc, g, c4d, cg12-month study exit biopsy
    Development IFTA from implantation to 12-monthsBanff ∆ ci, ct, cv12-month study exit biopsy
    Days from transplantation to clinical-biopsy proven rejectionTime to biopsy proven rejection2 weeks-12 months post-transplant
    Albuminuria >300mg/dayUrine albumin: Cr ratio6, 12, 24 and 60 months post-transplant
    Cost-effectiveness of urine CXCL10 monitoring strategyCosts of urine CXCL10 screening2 weeks-12 months post-transplant
    Quality of lifeEuroQOL (EQ-5DL)6 and 12 months post-transplant
    Urine CXCL10 kineticsChange in urine CXCL10 levels in response to rejection therapy2 weeks-12 months post-transplant

    Frequently Asked Questions

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    References

    Clinical Trials Gov: Urine CXCL10 Monitoring Trial in Kidney Transplant

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