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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03206801




Registration number
NCT03206801
Ethics application status
Date submitted
28/06/2017
Date registered
2/07/2017
Date last updated
1/12/2023

Titles & IDs
Public title
Urine CXCL10 Monitoring Trial in Kidney Transplant
Scientific title
A Randomized Controlled Trial of Urine CXCL10 Chemokine Monitoring Post-renal Transplant
Secondary ID [1] 0 0
364003
Secondary ID [2] 0 0
B2017:076
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Kidney Transplant; Complications 0 0
Rejection of Renal Transplant 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Surgery - Kidney transplant biopsy

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.

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.


Treatment: Surgery: 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 code [1] 0 0
Treatment: Surgery
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Death-censored graft loss
Timepoint [1] 0 0
2 weeks-12 months post-transplant
Primary outcome [2] 0 0
Clinical indication biopsy-proven acute rejection
Timepoint [2] 0 0
2 weeks-12 months post-transplant
Primary outcome [3] 0 0
De novo donor specific antibody development
Timepoint [3] 0 0
2 weeks-12 months post-transplant
Primary outcome [4] 0 0
Subclinical tubulitis
Timepoint [4] 0 0
12-month study exit biopsy
Primary outcome [5] 0 0
Interstitial fibrosis and inflammation (IFTA + i)
Timepoint [5] 0 0
12-month study exit biopsy
Secondary outcome [1] 0 0
Renal allograft function
Timepoint [1] 0 0
6, 12, 24 and 60 months post-transplant
Secondary outcome [2] 0 0
Microvascular inflammation
Timepoint [2] 0 0
12-month study exit biopsy
Secondary outcome [3] 0 0
Development IFTA from implantation to 12-months
Timepoint [3] 0 0
12-month study exit biopsy
Secondary outcome [4] 0 0
Days from transplantation to clinical-biopsy proven rejection
Timepoint [4] 0 0
2 weeks-12 months post-transplant
Secondary outcome [5] 0 0
Albuminuria >300mg/day
Timepoint [5] 0 0
6, 12, 24 and 60 months post-transplant
Secondary outcome [6] 0 0
Cost-effectiveness of urine CXCL10 monitoring strategy
Timepoint [6] 0 0
2 weeks-12 months post-transplant
Secondary outcome [7] 0 0
Quality of life
Timepoint [7] 0 0
6 and 12 months post-transplant
Secondary outcome [8] 0 0
Urine CXCL10 kinetics
Timepoint [8] 0 0
2 weeks-12 months post-transplant

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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 design
Purpose of the study
Other
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
3/04/2018
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
31/12/2025
Actual
Sample size
Target
420
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment postcode(s) [1] 0 0
5000 - Adelaide
Recruitment outside Australia
Country [1] 0 0
Canada
State/province [1] 0 0
Alberta
Country [2] 0 0
Canada
State/province [2] 0 0
Manitoba
Country [3] 0 0
Canada
State/province [3] 0 0
Ontario
Country [4] 0 0
Canada
State/province [4] 0 0
Quebec

Funding & Sponsors
Primary sponsor type
Other
Name
University of Manitoba
Address
Country
Other collaborator category [1] 0 0
Government body
Name [1] 0 0
Canadian Institutes of Health Research (CIHR)
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
Canadian National Transplant Research Program
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT03206801
Trial related presentations / publications
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Public notes

Contacts
Principal investigator
Name 0 0
Julie Ho, MD
Address 0 0
University of Manitoba
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Kiran Sran, MSc
Address 0 0
Country 0 0
Phone 0 0
204-787-3618
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT03206801