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Trial registered on ANZCTR


Registration number
ACTRN12624001205527
Ethics application status
Approved
Date submitted
9/09/2024
Date registered
1/10/2024
Date last updated
1/10/2024
Date data sharing statement initially provided
1/10/2024
Type of registration
Retrospectively registered

Titles & IDs
Public title
Detection of Kidney Transplant Medication Toxicity
Scientific title
Detecting Kidney Transplant Calcineurin Inhibitor Toxicity (the TransTox Study) in adult patients
Secondary ID [1] 310148 0
None
Universal Trial Number (UTN)
Trial acronym
TransTox
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Kidney Transplant 330719 0
Condition category
Condition code
Renal and Urogenital 327556 327556 0 0
Kidney disease

Intervention/exposure
Study type
Observational
Patient registry
True
Target follow-up duration
1
Target follow-up type
Years
Description of intervention(s) / exposure
Kidney transplantation and exposure to tacrolimus.
This study involves daily blood and urine sample collection of patients undergoing kidney transplantation, from one day before the transplant up to 30 days after (or earlier, if patient is discharged from the study hospital before postoperative day 30). Medical record information is also gathered, including daily tacrolimus dosage and blood levels, potential episodes of AKI after transplant and causes, such as rejection, infections or surgical complications, kidney biopsy results, long-term kidney function and damage, as measured by serum creatinine and urine albuminuria. The overall duration of observation is from time of enrolment for 12 months.
Intervention code [1] 326546 0
Diagnosis / Prognosis
Comparator / control treatment
No control group.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 335407 0
The primary outcome will be the number of histological alterations potentially related to tacrolimus toxicity (as a continuous measurement) at the 3-month protocolar kidney biopsy. The potential alterations include (1) isometric tubular vacuolation, (2) thrombotic microangiopathy, (3) arteriolar hyalinosis, (4) tubular atrophy, (5) interstitial fibrosis and (6) dystrophic calcification. The primary outcome will be the score represented by the number of the alterations at the 3-m kidney biopsy, from 0 to 6.
Timepoint [1] 335407 0
3-month protocolar kidney biopsy
Secondary outcome [1] 439546 0
AKI determined by the kidney biomarkers urinary KIM-1 AND urinary MCP-1 (composite):
urinary KIM-1 /urinary creatinine (uCr) > 0.1 ng/umol plus urinary MCP-1 /uCr> 0.01ng/umol
(levels based on the upper 95% percentile in studies performed by our group in healthy patients).
Timepoint [1] 439546 0
Daily, within the first 30 days after kidney transplantation.
Secondary outcome [2] 439979 0
AKI determined by the kidney biomarkers urinary KIM-1 AND urinary calbindin (composite):
urinary KIM-1 /urinary creatinine (uCr) > 0.1 ng/umol plus increased biomarker urinary calbindin /uCr> 1.97 ng/umol (levels based on the upper 95% percentile in studies performed by our group in healthy patients).
Timepoint [2] 439979 0
Daily, within the first 30 days after kidney transplantation.
Secondary outcome [3] 439980 0
AKI determined by the kidney biomarkers urinary KIM-1 AND urinary clusterin (composite):
urinary KIM-1 /urinary creatinine (uCr) > 0.1 ng/umol plus urinary clusterin /uCr>1.02ng/umol (levels based on the upper 95% percentile in studies performed by our group in healthy patients).
Timepoint [3] 439980 0
Daily, within the first 30 days after kidney transplantation.
Secondary outcome [4] 439981 0
AKI determined by the kidney biomarkers urinary KIM-1 AND urinary GSTp (composite):
urinary KIM-1 /urinary creatinine (uCr) > 0.1 ng/umol plus urinary GSTp /uCr> 3.67ng/umol (levels based on the upper 95% percentile in studies performed by our group in healthy patients).
Timepoint [4] 439981 0
Daily, within the first 30 days after kidney transplantation.
Secondary outcome [5] 439982 0
AKI determined by the kidney biomarkers KIM-1 AND urinary IL-18 (composite):
urinary KIM-1 /urinary creatinine (uCr) > 0.1 ng/umol plus urinary IL-18 /uCr> 0.003ng/umol (levels based on the upper 95% percentile in studies performed by our group in healthy patients).
Timepoint [5] 439982 0
Daily, within the first 30 days after kidney transplantation.
Secondary outcome [6] 439983 0
The number of histological alterations potentially related to tacrolimus toxicity (as a continuous measurement) at the 12-month protocolar kidney biopsy. The potential alterations include (1) isometric tubular vacuolation, (2) thrombotic microangiopathy, (3) arteriolar hyalinosis, (4) tubular atrophy, (5) interstitial fibrosis and (6) dystrophic calcification. This secondary outcome will be the score represented by the number of the alterations at the 12-m kidney biopsy, from 0 to 6.
Timepoint [6] 439983 0
At the 12-month protocolar kidney biopsy (12 months after kidney transplantation).
Secondary outcome [7] 439984 0
Long-term kidney function determined by serum creatinine
Timepoint [7] 439984 0
At 12 months after kidney transplantation

Eligibility
Key inclusion criteria
Adult patients undergoing kidney transplantation with no prior exposure to tacrolimus.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
age < 18 yo;
non-consent
transplant cancelled

Study design
Purpose
Natural history
Duration
Longitudinal
Selection
Convenience sample
Timing
Prospective
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Date of first participant enrolment
Anticipated
Actual
16/09/2022
Date of last participant enrolment
Anticipated
Actual
30/09/2024
Date of last data collection
Anticipated
4/12/2025
Actual
Sample size
Target
60
Accrual to date
Final
66
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 27084 0
Prince of Wales Hospital - Randwick
Recruitment postcode(s) [1] 43156 0
2031 - Randwick

Funding & Sponsors
Funding source category [1] 314310 0
Charities/Societies/Foundations
Name [1] 314310 0
Prince of Wales Hospital Foundation
Country [1] 314310 0
Australia
Primary sponsor type
Individual
Name
Professor Zoltan Endre, Nephrology Department at Prince of Wales Hospital
Address
Country
Australia
Secondary sponsor category [1] 316257 0
Charities/Societies/Foundations
Name [1] 316257 0
Prince of Wales Hospital Foundation
Address [1] 316257 0
Country [1] 316257 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 313420 0
South Eastern Sydney Local Health District HREC
Ethics committee address [1] 313420 0
https://www.seslhd.health.nsw.gov.au/services-clinics/directory/research-home/ethics
Ethics committee country [1] 313420 0
Australia
Date submitted for ethics approval [1] 313420 0
06/09/2021
Approval date [1] 313420 0
15/12/2021
Ethics approval number [1] 313420 0
2021/ETH11450

Summary
Brief summary
This is an observational study to discover and assess new markers in the blood or urine that detect early stages of kidney damage from the toxic effects of transplant anti-rejection medications (tacrolimus). Patients undergoing kidney transplantation with no prior exposure to tacrolimus are enrolled and daily blood and urine samples are collected for the first 30 days after the transplant.
The hypothesis is that we can better detect kidney toxicity caused by tacrolimus by using the new biomarkers studied here than by the standard clinical measurement of serum creatinine. This will allow our team to develop better protocols to determine tacrolimus dosage in clinical care within the first 30 days after kidney transplantation.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 128098 0
Prof Zoltan Endre
Address 128098 0
Prince of Wales Hospital, High Street, Randwick, NSW, 2031 - Nephrology Department, level 3
Country 128098 0
Australia
Phone 128098 0
+61 408 616 776
Fax 128098 0
Email 128098 0
[email protected]
Contact person for public queries
Name 128099 0
Prof Zoltan Endre
Address 128099 0
Prince of Wales Hospital, High Street, Randwick, NSW, 2031 - Nephrology Department, level 3
Country 128099 0
Australia
Phone 128099 0
+61 408 616 776
Fax 128099 0
Email 128099 0
[email protected]
Contact person for scientific queries
Name 128100 0
Zoltan Endre
Address 128100 0
Prince of Wales Hospital, High Street, Randwick, NSW, 2031 - Nephrology Department, level 3
Country 128100 0
Australia
Phone 128100 0
+61 408 616 776
Fax 128100 0
Email 128100 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
All de-identified data.
When will data be available (start and end dates)?
After study publication, no end date.
Available to whom?
To the whole scientific community.
Available for what types of analyses?
Any.
How or where can data be obtained?
International repositories via website (https://data.csiro.au/)


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.