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Trial registered on ANZCTR


Registration number
ACTRN12619000187145
Ethics application status
Approved
Date submitted
6/02/2019
Date registered
8/02/2019
Date last updated
11/02/2019
Date data sharing statement initially provided
8/02/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Comparison of two different surgical clamping techniques in patients undergoing nephrectomy for kidney cancer: a comparison of function and cancer outcomes
Scientific title
Early unclamping versus regular unclamping in robot assisted partial nephrectomy in patients with cT1 renal cell carcinoma: A multicentre, prospective, randomised controlled clinical trial of functional and oncological outcomes
Secondary ID [1] 295132 0
none
Universal Trial Number (UTN)
U1111-1227-5547
Trial acronym
P-NUT Trial
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Kidney cancer 308226 0
Condition category
Condition code
Cancer 307252 307252 0 0
Kidney
Surgery 307253 307253 0 0
Surgical techniques

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants in the intervention group will first complete a pre-operative medical history form with their treating surgeon, and undergo pre-operative blood and urine tests. They will then be referred to have a CT-scan and a DTPA renal scan at their treating hospital (or chosen radiology provider). Participants will then proceed to a robotic-assisted partial-nephrectomy surgery, incorporating the early unclamping of their renal blood vessels during surgery (unclamping before closure of the renal capsule, the 'intervention'), completed by their treating surgeon.

After surgery, intervention participants will complete a series of 6 post-operative blood and urine tests at set follow-up timepoints up to two years post-operative when visiting their surgeon for post-operative review/management appointments. They will also undergo post-operative CT-scan and DTPA renal scan at 6 months post-operative.

The control (comparator) group will undergo all these procedures as well, except their renal blood vessels will not be unclamped early during partial nephrectomy surgery (instead, unclamped after closure of the renal capsule).
Intervention code [1] 301460 0
Treatment: Surgery
Comparator / control treatment
Participants in the control group will first complete a pre-operative medical history form with their treating surgeon, and undergo pre-operative blood and urine tests. They will then be referred to have a CT-scan and a DTPA renal scan at their treating hospital (or chosen radiology provider). Participants will then proceed to a robotic-assisted partial-nephrectomy surgery, incorporating the regular unclamping of their renal blood vessels during surgery (unclamping after closure of the renal capsule, the 'comparator'), completed by their treating surgeon.

After surgery, control participants will complete a series of 6 post-operative blood and urine tests at set follow-up timepoints up to two years post-operative when visiting their surgeon for post-operative review/management appointments. They will also undergo post-operative CT-scan and DTPA renal scan at 6 months post-operative.
Control group
Active

Outcomes
Primary outcome [1] 318850 0
To assess the change in ipsilateral split renal function as demonstrated by DTPA renal scan (measured in percentages, between baseline and 6 months postoperative.
Timepoint [1] 318850 0
Baseline (pre-operative) and 6 months postoperative.
Secondary outcome [1] 366238 0
To assess post-operative changes in kidney function by mean change in eGFR (measured by DTPA scan in mL/min/1.73m^2) between baseline and 5 post-operative timepoints.
Timepoint [1] 366238 0
Baseline (pre-operative) and 6 weeks, 3 months, 6 months, 1 year and 2 years postoperative.
Secondary outcome [2] 366239 0
To assess post-operative changes in kidney function by mean change in urine Albumin-to-creatinine ratio (ACR) (measured by urine test in mg/g) between baseline and 5 post-operative timepoints.
Timepoint [2] 366239 0
Baseline (pre-operative) and 6 weeks, 3 months, 6 months, 1 year and 2 years postoperative.
Secondary outcome [3] 366240 0
To assess the percentage parenchymal renal mass preserved as measured on CT-abdomen at 6 months postoperative compared to baseline.
Timepoint [3] 366240 0
Baseline (pre-operative) and 6 months postoperative.
Secondary outcome [4] 366241 0
To assess the difference in positive surgical margins between early unclamping and regular clamping surgical procedures, as measured by histopathological analysis of cancer tissue removed intraoperatively.
Timepoint [4] 366241 0
Intra-operatively
Secondary outcome [5] 366242 0
To assess differences in intraoperative outcomes, (a composite outcome including warm ischemia time, total operative time, intraoperative blood loss (mL, measured by surgical drains) and complication rates) between early unclamping and regular clamping surgical procedures, as measured by intraoperative data collection forms.
(Complications to be assessed include: catastrophic bleeding incidence, blood transfusions, intra-operative conversion from robotic to either standard laparoscopic or open surgery, intra-operative visceral injury, excessive operative time, adverse reactions/incidents and patient death. These are unlikely to occur but will be monitored.)
Timepoint [5] 366242 0
Intraoperatively
Secondary outcome [6] 366243 0
To assess changes in non-neoplastic kidney parenchyma between early unclamping and regular clamping surgical procedures, as measured by histopathological analysis of kidney tissue (adjacent to cancer specimen) removed intraoperatively.
Timepoint [6] 366243 0
Intraoperaitvely

Eligibility
Key inclusion criteria
1. Adults aged 18 years and over;
2. Legally capable and competent to give written informed consent for participation;
3. Undergoing partial nephrectomy for a cT1 kidney tumor;
4. Elective procedure;
5. Healthy contralateral kidney;
6. RENAL score up to or equal to 8
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Patients unwilling or unable to undergo all pre- and post-operative evaluations as per protocol;
2. Anatomical or functional solitary kidney;
3. RENAL score > 8;
4. Radiological evidence of locally advanced and/or metastatic disease;
5. Dialysis-dependent chronic kidney disease (CKD stage 4+)
7. Contra-indications for contrast-enhanced computed tomography;
8. Coagulation disorders;
9. Patient or tumor factors precluding robotic surgery

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)
The consultant surgeon will contact the study coordinator at the lead site (RPAH). Patient details will be supplied, eligibility confirmed, and the patient enrolled into the trial before the treatment allocation is divulged. Since all surgeries are elective daytime procedures, consultants will contact the study coordinator at the lead site (RPAH) between 1 to 3 days before the surgery to confirm the treatment allocation.
Patients and study investigators will be blinded and won’t be able to know whether the procedure was performed with regular clamping or early unclamping. The surgeons performing the procedure will know the treatment allocation.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation of patients to study groups will occur using stratified block randomisation based on preoperative kidney function; no chronic kidney disease (CKD grade 0) versus chronic kidney disease (CKD grades 1-3a/b). Stratification and randomisation will be computer generated using REDCap.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
Demographic and clinical characteristics of patients will be summarised and presented using descriptive statistics. Perioperative outcomes (e.g. operative time / console time, conversion to open, blood loss, transfusion, and complications) will be compared between groups using student’s t-tests in case of numeric variables and chi-square tests or fisher’s exact test in binary variables. Postoperative functional renal outcomes will be compared between groups using independent student’s t-tests in case of numeric variables and chi-square tests or fisher’s exact test in binary variables. Multivariate modelling will be used to compare study outcomes after adjusting for potential confounders; a linear multi regression model for continuous variables and a logistic regression model for categorical variables. A p <0.05 will be considered as statistically significant.

Patients will be analyzed in the groups to which they were randomized in accordance with intention-to-treat principles. Missing data will be analysed to examine for randomness of omission. If the missing data is determined to be reasonably random, then predictive mean matching will be used for imputation. The distribution of the complete data set will be examined with and without the imputed data.

Subgroup analysis will be completed with covariates of sex, age, preoperative kidney function, experience of the surgeon and preoperative RENAL score for the primary and secondary endpoints. It is anticipated that there may not be sufficient variation for this analysis to be completed.

Other analysis will be performed to understand how regular and early unclamping will affect complication rate, blood loss, transfusion rate and preservation of parenchymal volume. This study is not powered to examine the effect size of any of these outcomes. However these data will be useful for future meta-analysis.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 11588 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [2] 13000 0
Liverpool Hospital - Liverpool
Recruitment hospital [3] 13001 0
Nepean Hospital - Kingswood
Recruitment hospital [4] 13002 0
St Vincent's Private Hospital (Darlinghurst) - Darlinghurst
Recruitment hospital [5] 13003 0
St George Private Hospital - Kogarah
Recruitment hospital [6] 13004 0
Macquarie University Hospital - Macquarie Park
Recruitment hospital [7] 13005 0
Concord Repatriation Hospital - Concord
Recruitment hospital [8] 13006 0
The Chris O’Brien Lifehouse - Camperdown
Recruitment postcode(s) [1] 23631 0
2050 - Camperdown
Recruitment postcode(s) [2] 25485 0
2170 - Liverpool
Recruitment postcode(s) [3] 25486 0
2747 - Kingswood
Recruitment postcode(s) [4] 25487 0
2010 - Darlinghurst
Recruitment postcode(s) [5] 25488 0
2217 - Kogarah
Recruitment postcode(s) [6] 25489 0
2109 - Macquarie Park
Recruitment postcode(s) [7] 25490 0
2139 - Concord

Funding & Sponsors
Funding source category [1] 299724 0
Government body
Name [1] 299724 0
Sydney Local Health District
Address [1] 299724 0
Level 11, KGV Building
Missenden Road
CAMPERDOWN NSW 2050

Mail Address:
Post Office Box M30
Missenden Road NSW 2050
Country [1] 299724 0
Australia
Funding source category [2] 301781 0
Government body
Name [2] 301781 0
Nepean Blue Mountains Local Health District
Address [2] 301781 0
Nepean Blue Mountains Local Health District
C/- Nepean Hospital
Derby Street
PENRITH NSW 2750
Country [2] 301781 0
Australia
Funding source category [3] 301785 0
Government body
Name [3] 301785 0
South Western Sydney Local Health District
Address [3] 301785 0
South Western Sydney Local Health District
C/-SWSLHD Executive Office
Locked Bag 7279
LIVERPOOL BC NSW 1871
Country [3] 301785 0
Australia
Primary sponsor type
Government body
Name
Sydney Local Health District
Address
Level 11, KGV Building
Missenden Road
CAMPERDOWN NSW 2050

Mail Address:
Post Office Box M30
Missenden Road NSW 2050
Country
Australia
Secondary sponsor category [1] 299765 0
Government body
Name [1] 299765 0
Nepean Blue Mountains Local Health District
Address [1] 299765 0
Nepean Blue Mountains Local Health District
C/- Nepean Hospital
Derby Street
PENRITH NSW 2750
Country [1] 299765 0
Australia
Secondary sponsor category [2] 301523 0
Government body
Name [2] 301523 0
South Western Sydney Local Health District
Address [2] 301523 0
South Western Sydney Local Health District
C/-SWSLHD Executive Office
Locked Bag 7279
LIVERPOOL BC NSW 1871
Country [2] 301523 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 302498 0
Sydney Local Health District Ethics Review Committee (RPA Zone)
Ethics committee address [1] 302498 0
Research Ethics and Governance Office
RPAH Medical Centre
Suite 210A, 100 Carillon Ave
Newtown NSW 2042
Ethics committee country [1] 302498 0
Australia
Date submitted for ethics approval [1] 302498 0
19/09/2018
Approval date [1] 302498 0
13/12/2018
Ethics approval number [1] 302498 0
HREC/18/RPAH/547 and X18-0389

Summary
Brief summary
The purpose of this study is to assess whether early unclamping during robot assisted partial nephrectomy surgery for kidney cancer is superior to regular clamping in maintaining renal function 6 months after surgery

Who is it for?
You may be eligible for this study if you are aged at least 18 years and are undergoing a partial nephrectomy for kidney cancer with one of the participating surgeons involved in this study.

Study details
Participants in this study will be randomised (by chance) into two groups. Both groups will have urine and blood tests, a CT-scan and a DTPA renal scan before surgery. Both groups will then undergo their planed partial nephrectomy procedure. One group will have their renal blood vessels unclamped at the regular (standard) time during the procedure, and the other group will have their renal blood vessels unclamped slightly earlier during the procedure. All participants will have repeat blood and urine tests at 6 timepoints over the 2 years following their surgery, and a repeat CT-scan and DTPA-scan at 6 months after their surgery.

It is intended that this study will help to find out which clamping technique (regular or early unclamping) is better for maintaining kidney function after partial nephrectomy surgery.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 84218 0
A/Prof Ruban Thanigasalam
Address 84218 0
Inner West Urology
12 Mary Street
Auburn 2144 NSW
Country 84218 0
Australia
Phone 84218 0
+61 2 9643 1223
Fax 84218 0
na
Email 84218 0
admin@innerwesturology.com.au
Contact person for public queries
Name 84219 0
A/Prof Ruban Thanigasalam
Address 84219 0
Inner West Urology
12 Mary Street
Auburn 2144 NSW
Country 84219 0
Australia
Phone 84219 0
+61 2 9643 1223
Fax 84219 0
na
Email 84219 0
admin@innerwesturology.com.au
Contact person for scientific queries
Name 84220 0
A/Prof Ruban Thanigasalam
Address 84220 0
Inner West Urology
12 Mary Street
Auburn 2144 NSW
Country 84220 0
Australia
Phone 84220 0
+61 2 9643 1223
Fax 84220 0
na
Email 84220 0
admin@innerwesturology.com.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?
De-identified individual participant data underlying published results only
When will data be available (start and end dates)?
Beginning 3 months and ending 5 years following main results publication.
Available to whom?
Only researchers who provide a methodologically sound proposal on a case-by-case basis at the discretion of Primary Sponsor and Chief investigators.
Available for what types of analyses?
Only to achieve the aims in the approved proposal.
By what mechanism will data be made available?
Access will be subject to approvals by Principal Investigator and approced proposals will require a signed data access agreement.
What supporting documents are/will be available?
No other documents available
Summary results
No Results