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Trial registered on ANZCTR


Registration number
ACTRN12618000787280p
Ethics application status
Submitted, not yet approved
Date submitted
6/04/2018
Date registered
9/05/2018
Date last updated
9/05/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
miniaturised-percutaneous nephrolithotomy (PCNL) versus flexible ureteropyeloscopy for treating kidney stone disease
Scientific title
A randomised controlled trial comparing mini-PCNL with flexible ureteropyeloscopy for urinary tract calculi
Secondary ID [1] 294521 0
None
Universal Trial Number (UTN)
U1111-1212-0249
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Kidney stone disease 307291 0
Urolithiasis 307292 0
Nephrolithiasis 307293 0
Condition category
Condition code
Surgery 306409 306409 0 0
Surgical techniques
Renal and Urogenital 306790 306790 0 0
Other renal and urogenital disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Description of intervention:
The intervention involves urinary tract calculi removal by one of two techniques that are described in detail below.

1. mini-PCNL
The patient is initially placed in lithotomy position under general or epidural anaesthesia and a 5 French ureteral catheter is placed up to the renal pelvis or onto the stone. The patient is then turned prone and a 19 gauge puncture needle is placed into the appropriate calyx under fluoroscopic guidance. A guidewire is inserted and fixed. and the puncture needle is then removed. After a 0.5–0.7 cm skin incision, dilation of the percutaneous tract is performed serially over the guidewire with a fascial dilator to 16–22 Fr.ench. A 12 French nephroscope is inserted into the kidney, and the holmium laser is applied for stone disintegration. Fragments are taken out by flushing or forceps. At the end of the surgery, a nephrotomy tube and a double J stent is placed at the surgeon's discretion. The stent is removed at 1 month using cystoscopy.

2. Flexible ureteropyeloscopy
The procedures are performed under general or epidural anaesthesia with the patient in lithotomy position. In some cases, a 6 French stent is placed 1 or 2 weeks before the procedure as a temporary measure to relieve acute obstruction from stones, infection, or uncontrolled pain due to stones; or to dilate the ureter of patients who have experienced unsuccessful insertion of ureteroscope before. If so, rigid ureteroscopy is performed to remove the pre-placed stent. Then a hydrophilic guidewire is placed to direct the placing of a ureteral access sheathmeasuring 12-14 French. Then the flexible ureteroscope is advanced through the sheath. The stones are fragmented with a holmium laser until debris below 4 mm is achieved. Fragments are removed with a basket as many as possible. A double-J stent is placed at the end of the procedure routinely and is removed at 1 month postoperatively.

Frequency and duration of procedure:
Both interventions aim to fully clear the stone in a single session. Both procedures typically take 60 to 90 minutes to complete.

Who will be administering the intervention:
Both interventions are performed by a consultant urologist. Dr Niall Davis will follow-up all patients that are recruited to monitor fidelity and objectively gather information on primary and secondary outcome variables.

Intervention code [1] 300823 0
Treatment: Surgery
Comparator / control treatment
The flexible ureteropyeloscopy arm of the study will form the comparator group as this is the most common technique for treating urinary tract calculi in Australia*

*Urolithiasis Treatment in Australia: The Age of Ureteroscopic Intervention.
Perera M, Papa N, Kinnear N, Wetherell D, Lawrentschuk N, Webb D, Bolton D.
J Endourol. 2016 Nov;30(11):1194-1199. Epub 2016 Oct 27.
PMID: 27629239
Control group
Active

Outcomes
Primary outcome [1] 305422 0
To compare stone-free rates (SFRs) and complication rates for both techniques. This is a composite primary outcome.

Complications will be classified according to the validated Clavien-Dindo grading system.*Clavien-Dindo grading will be measured from data recorded in patients' clinical notes, nursing notes and medication records.

Postoperative stone free rate will be evaluated at 1 month with a non-contrast CT KUB. This is standard practice for follow-up of urinary tract calculi for both techniques in our department. The success of treatment is defined as stone-free or residual fragments <4 mm at the 1-month postoperative visit.

* de la Rosette JJ, Opondo D, Daels FP, Giusti G, Serrano A, Kandasami SV, Wolf JS Jr, Grabe M, Gravas S, Group CPS (2012) Categorisation of complications and validation of the Clavien score for percutaneous nephrolithotomy. Eur Urol 62(2):246– 255.
Timepoint [1] 305422 0
Complications will be monitored during the entire peri-operative period (primary endpoint), at 1 month post-operatively, at 6-months post-operatively and at 12 months post-operatively in the outpatient department.

Stone free rate will be evaluated at 1 month post-operatively with a non-contrast CT KUB (primary endpoint)
Secondary outcome [1] 345132 0
To compare operative duration both both techniques. This will be recorded in minutes from when the patient has been anaesthetised until the surgeon inform the anaesthetist that the procedure has been completed.

There is a stopwatch present in each operation theatre for measuring operative duration.
Timepoint [1] 345132 0
Operative duration will be recorded in minutes during the peri-operative period
Secondary outcome [2] 346492 0
To compared duration of inpatient stay with both techniques. This outcome will be assessed from admission and discharge time points that are routinely recorded in patients' hospital records
Timepoint [2] 346492 0
This will be recorded in days from when the patient is admitted to hospital until their discharge
Secondary outcome [3] 346493 0
To compare Haemoglobin drop between both techniques. This will be recorded on a serum Full Blood Count (FBC) sample. Patients routinely have an FBC performed before and after both procedures have taken place
Timepoint [3] 346493 0
This will be checked and recorded 24 hours after the procedure has taken place
Secondary outcome [4] 346494 0
To compare analgesic requirements between both techniques. This data will be recorded from patient's medication records (i.e. Drug Kardex)
Timepoint [4] 346494 0
All analgesic requirements will be documented during inpatient stay for both techniques.

Eligibility
Key inclusion criteria
RECRUITMENT PROCEDURE
Eligible patients are consecutive patients who presented to the urology outpatient department with a proximal ureteric and/ or greater than 1 intrarenal calculus that is greater than 0.5cm requiring intervention due to symptoms such as pain or recurrent urinary tract infections., and in whom flexible ureteropyeloscopy or mini-PCNL is planned.

INCLUSION CRITERIA
Eligible patients are patients with proximal ureteral or intra-renal stones greater than 0.5 cm in size referred to our institute will be considered for this study. The proximal ureter is defined as the portion extending from the ureteropelvic junction to the lower border of the fourth lumbar vertebra.
Minimum age
18 Years
Maximum age
75 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
EXCLUSION CRITERIA
Patients with urogenital anomaly, solitary kidney, age <18 years, age >75 years or coagulopathy will be excluded.

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)
Sealed opaque envelopes
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
A simple randomisation procedure will be performed by selecting a sealed envelope with the name of the procedure that is intended for a patient. The operating consultant urologist will select each sealed envelope and be blinded to the data contained in the sealed envelope.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
In a preliminary analysis of our stone database, the response within each treatment group was normally distributed, and the standard deviation was 9. The true difference of surgical success rate was 6.5%. Type I error probability was 0.05 associated with the test of this null hypothesis. Therefore, we need to study 31 subjects in each group to be able to reject the null hypothesis that the surgical success rates of mini-PCNL and pyelsocopy groups are equal with a probability of 0.8. The follow-up rate of patients is estimated at 10%. Finally, the sample size is 35 cases in each group.

Recruitment
Recruitment status
Not yet 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)
VIC
Recruitment hospital [1] 10579 0
Austin Health - Austin Hospital - Heidelberg
Recruitment postcode(s) [1] 22298 0
3084 - Heidelberg

Funding & Sponsors
Funding source category [1] 299144 0
Hospital
Name [1] 299144 0
The Austin Hospital
Address [1] 299144 0
145 Studley Rd,
Heidelberg
Melbourne
VIC 3084
Country [1] 299144 0
Australia
Primary sponsor type
Individual
Name
Mr Greg Jack
Address
Mr Greg Jack
Consultant Urologist
Department of Urology
8th Floor, Harold Stokes Building
The Austin Hospital
Heidelberg 3084
Melbourne
Victoria
Country
Australia
Secondary sponsor category [1] 298405 0
None
Name [1] 298405 0
Address [1] 298405 0
Country [1] 298405 0

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 300074 0
Austin Health: Human Research Ethics Committee
Ethics committee address [1] 300074 0
Office for Research
Austin Hospital
L8 Harold Stokes Building
145 Studley Road
PO Box 5555 Heidelberg
Victoria Australia 3084
Ethics committee country [1] 300074 0
Australia
Date submitted for ethics approval [1] 300074 0
05/04/2018
Approval date [1] 300074 0
Ethics approval number [1] 300074 0

Summary
Brief summary
LAY SUMMARY
Mini-percutanoeus nephrolithotomy (mini-PCNL) and flexible ureteropyeloscopy are commonly used techniques for treating ureteral and renal stones. Both treatment options are invasive and are associated with complications. There are only a few studies that compare these two treatment modalities. Both modalities are associated with reasonable postoperative stone free rates with minimal complications. Immediate stone free rate is higher with mini-PCNL but comparable in both modalities at 1 month. Pyeloscopy is associated with favourable pain scores and lower haemoglobin drop. We aim to compare both techniques to definitively investigate whether one modality is superior than the other.

HYPOTHESIS
Few prospective randomised controlled trials have compared mini-PCNL and flexible ureteropyeloscopy for treating renal and proximal ureteral stones.Furthermore, no specific guideline is available regarding the optimal surgical management of renal stones and proximal ureteral stones. We hypothesise that one modality is associated with a greater stone free rate and lower complication rate compared to the other modality for managing nephrolithiasis

STUDY AIMS:
To compare stone free rate and surgical parameters between flexible ureteropyeloscopy mini-PCNL and RIRS in the management of renal stones and proximal ureteral stones >5 mm in a single session.

OUTCOME MEASURES
The primary end-point in this study is stone free rate (SFR) in a single session. Before a 3-month follow-up visit, all patients will undergo a low-dose non-contrast CT scan to assess for the presence of residual stone. Stone free status is defined as no residual stones or stones within 3 months postoperatively. The secondary outcomes are intraoperative and postoperative parameters such as operation time, hemoglobin drop, analgesic requirement, hospital stay, and complications. Complications will be evaluated according to the Clavien classification of surgical complications.
We have published a systematic review and meta-analysis as part of the background information and research to this randomized controlled trial and have attached it to our application:
World J Urol. 2018 Feb 16. doi: 10.1007/s00345-018-2230-x.
MINIATURISED PERCUTANEOUS NEPHROLITHOTOMY VERSUS FLEXIBLE URETEROPYELOSCOPY: A SYSTEMATIC REVIEW AND META-ANALYSIS COMPARING CLINICAL EFFICACY AND SAFETY PROFILE.
Davis NF1, Quinlan MR2, Poyet C2, Lawrentschuk N2, Bolton DM2, Webb D2, Jack GS2.

Our systematic review and meta-analysis provides a detailed and accurate comparative analysis on mini-PCNL and FURS. We found that modifications and advancements in equipment design will continue to improve the performance of both techniques. The continuing evolution of both urological technologies, should facilitate high levels clinical efficacy while maintaining high safety profiles.
Trial website
Trial related presentations / publications
Public notes
Attachments [1] 2569 2569 0 0
Attachments [2] 2570 2570 0 0

Contacts
Principal investigator
Name 82482 0
Mr Greg Jack
Address 82482 0
Consultant Urologist
Department of Urology
Level 8, Harold Stokes Building
The Austin Hospital
Heidelberg 3084
Melbourne
VIC
Country 82482 0
Australia
Phone 82482 0
+61 415 179 969
Fax 82482 0
Email 82482 0
gregory.jack@austin.org.au
Contact person for public queries
Name 82483 0
Mr Greg Jack
Address 82483 0
Consultant Urologist
Department of Urology
Level 8, Harold Stokes Building
The Austin Hospital
Heidelberg 3084
Melbourne
VIC
Country 82483 0
Australia
Phone 82483 0
+61 415 179 969
Fax 82483 0
Email 82483 0
gregory.jack@austin.org.au
Contact person for scientific queries
Name 82484 0
Mr Greg Jack
Address 82484 0
Consultant Urologist
Department of Urology
Level 8, Harold Stokes Building
The Austin Hospital
Heidelberg 3084
Melbourne
VIC
Country 82484 0
Australia
Phone 82484 0
+61 415 179 969
Fax 82484 0
Email 82484 0
gregory.jack@austin.org.au

No data has been provided for results reporting
Summary results
Not applicable