Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12622001093774
Ethics application status
Approved
Date submitted
15/07/2022
Date registered
8/08/2022
Date last updated
1/02/2023
Date data sharing statement initially provided
8/08/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
Personalised Post-operative monitoring and fluid therapy vs standard of care in recipients of Living donor kidney transplant
Scientific title
Pilot Randomised Controlled Trial of Personalised Goal Directed Therapy after Adult Living Donor Kidney Transplant.
Secondary ID [1] 307552 0
Nil Known
Universal Trial Number (UTN)
U1111-1280-3038
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Kidney failure 326991 0
Kidney Transplantation 326992 0
Condition category
Condition code
Renal and Urogenital 324179 324179 0 0
Kidney disease
Surgery 324180 324180 0 0
Other surgery
Public Health 324359 324359 0 0
Health service research

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
There is currently clinical equipose on management of recipients of kidney transplants postoperatively between high acuity or ward based environments.

Patients in the intervention arm will be admitted post operatively into the Advanced Recovery Room within the Royal Adelaide Hospital, for monitoring for 24 hours post operatively. The parameters that will be monitored will include a variety of haemodynamic measures, such as blood pressure, central venous pressure and mean arterial pressure. In addition, novel haemodynamic monitoring using the ClearSight™ and FloTrac™ devices (Edwards Lifescience™) will enable capture of, via the EV1000 Clinical Monitoring Platform, more advanced haemodynamic monitoring such as cardiac index and pulse pressure variation. Markers of end organ perfusion such as capillary refill time, urine output and serum haemoglobin and lactate will also be used in the multimodal haemodynamic assessment. Interpretation of the urine output trend, haemoglobin trend and lactate trend will rely on clinical judgement. A more detailed intervention protocol and assessment algorithm is available in Appendix 2 and 5 within the attached study protocol.
Arterial lines will be placed if clinically indicated, at the judgement of clinician

The entirety of the intervention will be delivered under the direct supervision of the personnel below.
Personnel involved in care will be
• Renal speciality nurse – rostered to 1:1 patient care as “nursing special” for 24 hours post transplantation
• Advanced Recovery nurse – will assist with haemodynamic monitoring and use of vasopressors
• Renal resident medical officer – on site 24 hours
• Advanced recovery RMO – will assist with clinical reviews
• Renal registrar – on call 24 hours
• Anaesthetist– on call 24 hours
• Transplant nephrologist - on call 24 hours
• Other consulting clinicians as required.

The proposed post-operative targets are as below
Systolic blood pressure > 100 - As per both Clearsight AND non-invasive blood pressure (BP)
MAP > 70 as per Clearsight device
Stroke Volume Variation < 13% as per Clearsight device
Haemoglobin trend acceptable, as interpreted by bedside clinician
Urine Output acceptable, as interpreted by bedside clinician
Lactate trend acceptable (If arterial line in situ) - as interpreted by bedside clinician
Capillary refill time less than 2 secs

Review of patient medical record will be undertaken to ensure adherence with study protocol.
At the end of the study period, participants will be managed on the kidney ward.
Intervention code [1] 324014 0
Treatment: Other
Comparator / control treatment
Patients in the control arm will receive current standard of care, as per the Central Adelaide Local Health Network Renal Transplant: Post-Operative Management protocol (CNARTS-PRC03932).
Personnel involved in care will be
• Renal speciality nurse – rostered to 1:1 patient care as “nursing special” for 24 hours post transplantation
• Renal resident medical officer – Basic Physician Trainee, employed by the Royal Adelaide Hospital, on site 24 hours.
• Renal registrar – Renal Advanced Trainee, employed by Central and Northern Adelaide Renal and Transplantation Service, on call 24 hours.
• Transplant nephrologist - employed by Central and Northern Adelaide Renal and Transplantation Service, on call 24 hours.
• Other consulting clinicians as required.
Control group
Active

Outcomes
Primary outcome [1] 331995 0
Safety end point
Adverse event reporting – defined as harm resulted to a person receiving healthcare and stratified using the Severity Assessment Codes
Timepoint [1] 331995 0
3 months post operatively
Primary outcome [2] 331996 0
Feasibility end point - composite primary outcome of rate of enrolment into the study, measured against all living donor kidney transplant performed at the Royal Adelaide Hospital, and adherence to study protocol.

Rate of enrolment will be assessed via audit of study recruitment logs.
Adherence to study protocol can be measured objectively by real time data recording at the time of intervention as well as semi structured interviews (performed at 6 months) with renal nurses and ARRC staff
Timepoint [2] 331996 0
At conclusion of study
Primary outcome [3] 331997 0
Efficacy End point
Difference between average 24 hour mean arterial pressure – calculated by comparing the area under the curve of mean arterial pressure over time.
Measured at the same intervals in both groups. recorded via electronic medical record
Timepoint [3] 331997 0
At conclusion of study
Secondary outcome [1] 411863 0
Incidence of hypotension – recorded via electronic medical record
Timepoint [1] 411863 0
48 Hours post operatively
Secondary outcome [2] 411864 0
Duration of hypotension – Measured in 30-minute blocks. Recorded via electronic medical record
Timepoint [2] 411864 0
48 hours post operatively
Secondary outcome [3] 411865 0
Incidence of slow graft function – defined by ANZDATA definition. Recorded via electronic medical record
Timepoint [3] 411865 0
48 hours post operatively
Secondary outcome [4] 411866 0
Adverse graft outcomes – composite outcome of graft thrombosis, graft loss within 30 days, urine leak, urinary tract obstruction and rejection or wound complications requiring intervention.
Recorded via electronic medical record
Timepoint [4] 411866 0
30 days post operatively
Secondary outcome [5] 411867 0
Vasopressor use – defined by the amount of vasopressor use in the first 24-hour post operatively, measured in mg. Metaraminol with be the preferred vasopressor use.
Recorded via electronic medical record
Timepoint [5] 411867 0
24 hours post operatively
Secondary outcome [6] 411868 0
Urine output volume within the first 24 hours
Recorded via electronic medical record
Timepoint [6] 411868 0
24 hours post operatively
Secondary outcome [7] 411869 0
Length of stay – From elective admission to hospital until discharge from hospital
Recorded via electronic medical record
Timepoint [7] 411869 0
30 days post operatively
Secondary outcome [8] 411870 0
Number of ICU admissions – defined by admission to the intensive care unit within 48 hours post operatively
Recorded via electronic medical record
Timepoint [8] 411870 0
48 hours post operatively

Eligibility
Key inclusion criteria
Adult (18 years of age or older) patients undergoing living donor kidney transplantation, who are able to provide written consent.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patient requiring peri-operative plasma exchange for either high Angiotensin II Receptor Type 1 antibodies or pre-formed Human Leukocyte Antigen (HLA) antibodies. These patients may require post operative plasma exchange, which may not be able to be delivered in a timely fashion to the intervention arm with current levels of resourcing.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocations will be concealed using the randomisation module in RedCap. An external statistician will generate the randomisation sequence and upload it to the RedCap module. The sequence will be locked and masked, and will not be accessible to the investigators.

Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The randomisation sequence will be generated externally by a statistical consultant using permuted block randomisation, with variable block sizes.
Participants will be stratified based on hypertension, defined as the use of one or more antihypertensive agents.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Safety
Statistical methods / analysis
Frequencies, expressed as percentages, will be reported for categorical variables.
The measures of central tendencies will be calculated for continuous demographic data; reported as mean and standard deviations for normally distributed variables and median and interquartile range for non-normally distributed data.
The difference between groups will be assessed using either t test or Wilcoxon rank sum test for continuous variables and chi-squared test for categorical variables.
The primary efficacy end point, namely the difference in mean 24-hour blood pressure between the control and intervention groups will be compared using generalised estimating equations

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
15/02/2023
Actual
Date of last participant enrolment
Anticipated
31/01/2024
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
24
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 22802 0
The Royal Adelaide Hospital - Adelaide
Recruitment postcode(s) [1] 38088 0
5000 - Adelaide

Funding & Sponsors
Funding source category [1] 311826 0
Hospital
Name [1] 311826 0
Royal Adelaide Hospital
Country [1] 311826 0
Australia
Primary sponsor type
Other Collaborative groups
Name
Kidney, Transplant and Diabetes Research Australia
Address
Level 1, 62 Woodville Road Woodville, SA 5011
Country
Australia
Secondary sponsor category [1] 313301 0
None
Name [1] 313301 0
Address [1] 313301 0
Country [1] 313301 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 311269 0
Central Adelaide Local Health Network Human Research Ethics
Ethics committee address [1] 311269 0
Port Road
Adelaide SA 5000
Ethics committee country [1] 311269 0
Australia
Date submitted for ethics approval [1] 311269 0
15/08/2022
Approval date [1] 311269 0
27/12/2022
Ethics approval number [1] 311269 0
2022/HRE00180

Summary
Brief summary
Chronic Kidney Disease affects 1 in 10 Australian adults, with almost 15,000 Australians relying on dialysis to survive. Kidney transplantation provides better quality of life and long-term survival, in addition to being more cost effective when compared to dialysis. However, transplantation requires major surgery, which is associated with a number of serious risks and adverse events. One such adverse event is hypotension, or low blood pressure, after the operation, which may starve the newly transplanted kidney of oxygen and nutrients in the critical post-transplant period. The effect of this low blood pressure on short, medium and long term kidney transplant function is unknown. The best way to prevent, monitor and treat low blood pressure during this period is also unknown.

The care of a new kidney transplant in the first 24 hours of the operation is very important. Parameters such as blood pressure, the amount of fluid delivered and the amount of urine produced make all have an impact on how well a new transplant kidney works in the immediate post operative period. Optimisation of these parameters may have an impact on long-term kidney transplant function.
This is a pilot study looking at different way that patients can be monitored after kidney transplant. The study would aim to compare current protocols against additional methods of monitoring blood pressure and fluid status, to see if this leads to better outcomes.

This study is a randomised trial. Participants will be randomised to 1 of 2 post operative care models.

One model is the current standard Royal Adelaide Hospital post transplantation management protocol, which will involve being managed on the kidney ward with a team of kidney doctors and nurses after time spent in recovery.

The second model will involve participants being admitted to a specialised advanced recovery area for 24 hours after kidney transplantation. Participants will have regular observations and occasional blood tests. The study may require the placement of an arterial line, which is a line that can be used for intensive blood pressure monitoring and blood taking without the need for additional venepuncture. After the operation, participants will be monitored carefully by a team consisting of kidney doctors, recovery nurses and kidney nurses trained in post-transplant care. After 24 hours, participants will move to the kidney ward.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 120518 0
Dr Karthik Venkataraman
Address 120518 0
Central and Northern Adelaide Renal and Transplantation Service, Level 7F
Royal Adelaide Hospital, Port Rd, Adelaide, SA, 5000
Country 120518 0
Australia
Phone 120518 0
+61430495079
Fax 120518 0
Email 120518 0
karthik.venkataraman@sa.gov.au
Contact person for public queries
Name 120519 0
Dr Michael Collins
Address 120519 0
Central and Northern Adelaide Renal and Transplantation Service, Level 7F
Royal Adelaide Hospital, Port Rd, Adelaide, SA, 5000
Country 120519 0
Australia
Phone 120519 0
+61474871437
Fax 120519 0
Email 120519 0
michael.collins@sa.gov.au
Contact person for scientific queries
Name 120520 0
Dr Michael Collins
Address 120520 0
Central and Northern Adelaide Renal and Transplantation Service, Level 7F
Royal Adelaide Hospital, Port Rd, Adelaide, SA, 5000
Country 120520 0
Australia
Phone 120520 0
+61474871437
Fax 120520 0
Email 120520 0
michael.collins@sa.gov.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Individual participant data that underlie the results reported in the primary publication, after de-identification (text, tables, figures and appendices) will be available for individual participant data meta-analysis.
When will data be available (start and end dates)?
Start date: Data will be available 12 months post main publication
End Date: 15 years (data destruction)
Available to whom?
Researchers who provide a methodologically sound proposal will be assessed on a case-by-case basis, and data will be released at the discretion of the principle
Available for what types of analyses?
Meta-analyses
How or where can data be obtained?
Access subject to approvals by Principal Investigator (karthik.venkataraman@sa.gov.au)


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
16618Study protocol    384365-(Uploaded-14-07-2022-13-25-02)-Study-related document.docx
16619Informed consent form    384365-(Uploaded-14-07-2022-13-25-33)-Study-related document.docx
18017Ethical approval    384365-(Uploaded-09-01-2023-14-42-11)-Study-related document.pdf



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.