Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12623001166662
Ethics application status
Approved
Date submitted
18/09/2023
Date registered
10/11/2023
Date last updated
16/11/2023
Date data sharing statement initially provided
10/11/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
How many people suffer from bowel problems following surgery for colorectal cancer, and what treatments are the best for managing these problems?
Scientific title
Comparing sacral neuromodulation (SNM) and transanal irrigation (TAI) against optimised conservative management (OCM) for the treatment of major Low Anterior Resection Syndrome (LARS) in patients who have had an anterior resection for bowel cancer - Pathway of low anterior resection syndrome relief after surgery (POLARiS) trial
Secondary ID [1] 310624 0
The University of Sydney NHMRC Clinical Trials Centre CTC0391
Universal Trial Number (UTN)
Trial acronym
POLARiS
Linked study record
This record describes the Australian-specific recruitment of the POLARIS study which is also being conducted in the UK (ISRCTN12834598). The ISRCTN12834598 record describes the UK-based recruitment details.

Health condition
Health condition(s) or problem(s) studied:
Low anterior resection syndrome 331503 0
Bowel Cancer 331853 0
Condition category
Condition code
Cancer 328238 328238 0 0
Bowel - Back passage (rectum) or large bowel (colon)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
There are two parts to the POLARiS Study. The POLARiS cohort and the POLARiS randomised control trial (RCT). The Cohort part of the POLARiS Study will ask people who have had an anterior resection for bowel cancer in the last 10 years about their quality of life and bowel symptoms every three months over a two-year period. It will take around 30 minutes to complete the full set of questionnaires at each timepoint. The cohort study aims to identify how many people are affected by LARS and to see how LARS impacts on their quality of life. It will also allow us to understand more about how LARS changes over time. At the time people join the cohort study, they might not know their LARS status. We expect nearly one in three, or one third (1/3), of the cohort study group will develop major LARS over their two-year study period. There will be no physical assessments for participants in the cohort except for at registration which could be done in-person.

The POLARiS Study randomised controlled trial (RCT) part will include participants identified as having major LARS symptoms which have not been managed by previous or current treatment. The purpose of this part of the POLARiS study is to see how well the study treatment for LARS works and to determine if there is a ’best’ treatment overall. POLARiS is comparing sacral neuromodulation (SNM) and transanal irrigation (TAI) against optimised conservative management (OCM) for the treatment of major LARS. There are two primary comparisons for the randomised controlled trial - i) SNM versus OCM and ii) TAI versus OCM.

Arm 1: Participants randomised to TAI will attend a one-hour practical education session with a specialist nurse where the device and volume will be decided.
Potential devices: Aquaflush, Peristeen, Qufora IrriSedo Cone, Qufora IrriSedo Mini
Irrigation fluid: body temperature water
Duration & Frequency: 20-35min process every 24-48hrs post-randomisation for 24 months post-randomisation.
Mode of administration: Self-administer at home.
Adherence monitoring: clinical assessment at 3 months post-randomisation, then telephone assessments every 3 months until 12 months post-randomisation, then data collection from medical notes at 24 months post-randomisation.

Arm 2: Participants randomised to SNM will have a consultation with their local clinician performing the SNM procedure.
Sacral neuromodulation involves a minor surgical procedure under anaesthetic to insert a wire close to the sacral nerve, which is in the lower part of the back above the buttocks. The device works by improving the signaling between your muscles and your nerves to help with pelvic floor muscle strength and coordination.
Potential devices: Axonics Neurostimulator, InterStim Neurostimulator Model 3058
Insertion procedure: Prior to being fitted with a permanent SNM device, a temporary wire is inserted. This will act as a test device to see if there is any improvement in symptoms over a 2-week period. If symptoms are improved with the temporary SNM device, participants will be offered to be fitted with a permanent device. This is usually done as a day case procedure under anaesthetic but will vary depending on local hospital practice. Once fitted with a permanent SNM device, it does not need to be removed unless there is an issue with the device, or the wire moves. The battery will need changing but the timing of this will vary depending on the type. It can also be removed if the participant no longer wants the device or finds it no longer useful in managing symptoms.
Adherence monitoring: clinical assessment at 3 months post-randomisation, then telephone assessments every 3 months until 12 months post-randomisation, then data collection from medical notes at 24 months post-randomisation.

Participants will complete questionnaires designed to capture health-related quality of life at baseline and 3 monthly throughout the 24-month follow-up period.

Participants randomised to the RCT are given the opportunity to take part in up to 3 semi-structured interviews to explore the impact of the interventions.
Intervention code [1] 327025 0
Treatment: Devices
Intervention code [2] 327026 0
Rehabilitation
Comparator / control treatment
Arm 3: Participants in the Optimised Conservative Manangement group will have a consultation with a clinical member of the study where appropriate treatments will be instigated.
Examples of OCM options: Practical support & advice given by the treating doctor, dietician consultations, medications, physiotherapy.
Frequency and duration of treatments will vary depending on the participant and the health professional treating the participant.
Mode of administration: one-on-one face-to-face consultation.
Adherence monitoring: clinical assessment at 3 months post-randomisation, then telephone assessments every 3 months until 12 months post-randomisation, then data collection from medical notes at 24 months post-randomisation.
Control group
Active

Outcomes
Primary outcome [1] 336108 0
LARS symptoms
Timepoint [1] 336108 0
Baseline and every 3 months until 24 months post registration/randomisation
Secondary outcome [1] 426852 0
RCT and Cohort groups: Health-related quality of life
Timepoint [1] 426852 0
Baseline and at 3, 6, 12 and 24 months after registration/randomisation
Secondary outcome [2] 426853 0
RCT and Cohort groups: Incidence of adverse events related to the trial/trial procedures
Timepoint [2] 426853 0
RCT group: Adverse events will be reviewed every 3 months up to 12 months post-randomisation, and then at 24 months post-randomisation.
Cohort group: Adverse events will be reviewed annually up to 24 months post-registration.
Secondary outcome [3] 426854 0
RCT group only: Generic quality of life
Timepoint [3] 426854 0
Baseline, 3, 6, 12 and 24 months after randomisation
Secondary outcome [4] 426855 0
RCT group only: Treatment compliance
Timepoint [4] 426855 0
Compliance will be reviewed every 3 months up to 12 months post-randomisation, then at 24 months post-randomisation.
Secondary outcome [5] 426856 0
RCT group only: Cost-effectiveness of the treatment
Timepoint [5] 426856 0
Baseline, 3, 6, 12 and 24 months after randomisation
Secondary outcome [6] 426857 0
RCT group only: Impact of participation
Timepoint [6] 426857 0
Up to 6 weeks after randomisation, 3 months after commencing treatment, and 12 months after randomisation
Secondary outcome [7] 426859 0
Employment status
Timepoint [7] 426859 0
Baseline, 3, 6, 12 and 24 months after randomisation
Secondary outcome [8] 427436 0
RCT and Cohort groups: Health-related physical functioning
Timepoint [8] 427436 0
Baseline and at 3, 6, 12 and 24 months after registration/randomisation
Secondary outcome [9] 427437 0
RCT and Cohort groups: Health-related psychological functioning
Timepoint [9] 427437 0
Baseline and at 3, 6, 12 and 24 months after registration/randomisation
Secondary outcome [10] 427438 0
RCT and Cohort groups: Health-related emotional functioning
Timepoint [10] 427438 0
Baseline and at 3, 6, 12 and 24 months after registration/randomisation
Secondary outcome [11] 427696 0
Time lost from productive activities
Timepoint [11] 427696 0
Baseline, 3, 6, 12 and 24 months after randomisation.

Eligibility
Key inclusion criteria
General inclusion criteria (cohort):
1. Diagnosis of rectal or sigmoid cancer
2. Low or high anterior resection (colorectal resection with anastomosis to the rectum)
3. Functioning anastomosis
4. Primary surgery less than 10 years before recruitment
5. At least 6 months since reversal of stoma or primary surgery if no stoma created
6. Aged greater than or equal to 18 years old
7. Able to provide written informed consent

RCT inclusion criteria - as above plus:
8. Major LARS symptoms within the last 3 months (Defined as a LARS score of greater than or equal to 30)
9. Clinically appropriate for randomisation as determined by the treating clinician
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Cohort exclusion criteria:
1. Receiving ongoing chemotherapy, radiotherapy or immunotherapy treatment for cancer
2. Anterior exenteration

RCT Exclusion criteria - as above plus:
3. Receiving ongoing chemotherapy, radiotherapy or immunotherapy treatment for cancer
4. Metastatic disease
5. Inflammatory bowel disease
6. Pregnancy
7. Use of TAI for LARS within 1 month prior to randomisation
8. Not eligible for SNM and not eligible for TAI
9. Anterior exenteration
10. Anastomotic stricture
11. History of anastomotic leak with evidence of ongoing leak/sinus

Plus treatment-specific exclusions:
Exclusion criteria for SNM:
12. Site unable to offer SNM as a treatment
13. Previous SNM
14. Specific contraindications to implantation
15. Any other contraindications advised by the care team, product manufacturer or distributor

Exclusion criteria for TAI:
16. Unable to perform TAI
17. History of anastomotic leak with evidence of ongoing leak/sinus
18. Previous or current use of TAI for LARS
19. Site unable to offer TAI as a treatment
20. Any other contraindications advised by the care team, product manufacturer or distributor

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)
Allocation is not concealed
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computer-generated minimisation programme incorporating a random element to ensure treatment groups are well-balanced for participant characteristics.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Not Applicable
Type of endpoint/s
Statistical methods / analysis
Analyses of the RCT will be conducted on an intention-to-treat basis, where all patients are analysed according to their randomised treatment, unless otherwise stated. Hypothesis tests will be 2-sided at the 5% level of significance. Point estimates of treatment effects will be reported with 2-sided 95% confidence intervals.
Comparative effectiveness analyses for each endpoint will consist of two pairwise treatment comparisons: TAI vs OCM and SNM vs OCM. Treatment groups will be combined across different randomisation options for gains in efficiency.
Let R1, R2 and R3 denote the randomisation options SNM:TAI:OCM, TAI:OCM and SNM:OCM respectively. The TAI vs OCM comparison will include patients from R2 and patients from R1 who were assigned to either TAI or OCM. SNM vs OCM comparison will include patients from R3 and patients from R1 who were assigned to either SNM or OCM.
Analysis of the cohort data will include exploratory model-fitting to evaluate the longitudinal trends in LARS scores in relation to patient characteristics and clinical data, as well as the identification of potential risk factors for major LARS.
Non-linearity of effects of continuous explanatory variables in all models will be considered, and explored and fitted as required via fractional polynomials or appropriate alternative.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/12/2023
Actual
Date of last participant enrolment
Anticipated
1/03/2026
Actual
Date of last data collection
Anticipated
1/03/2028
Actual
Sample size
Target
700
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,WA,VIC
Recruitment hospital [1] 25535 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [2] 25536 0
Concord Repatriation Hospital - Concord
Recruitment hospital [3] 25537 0
St George Hospital - Kogarah
Recruitment hospital [4] 25538 0
The Chris O’Brien Lifehouse - Camperdown
Recruitment hospital [5] 25539 0
Bankstown-Lidcombe Hospital - Bankstown
Recruitment hospital [6] 25540 0
Royal Brisbane & Womens Hospital - Herston
Recruitment hospital [7] 25541 0
Queen Elizabeth II Jubilee Hospital - Coopers Plains
Recruitment hospital [8] 25542 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [9] 25543 0
Redcliffe Hospital - Redcliffe
Recruitment hospital [10] 25544 0
Barwon Health - Geelong Hospital campus - Geelong
Recruitment hospital [11] 25545 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment hospital [12] 25546 0
St Vincent's Hospital (Melbourne) Ltd - Fitzroy
Recruitment hospital [13] 25547 0
Austin Health - Austin Hospital - Heidelberg
Recruitment hospital [14] 25863 0
Royal Perth Hospital - Perth
Recruitment hospital [15] 25864 0
St John of God Hospital, Subiaco - Subiaco
Recruitment postcode(s) [1] 41357 0
2050 - Camperdown
Recruitment postcode(s) [2] 41358 0
2139 - Concord
Recruitment postcode(s) [3] 41359 0
2217 - Kogarah
Recruitment postcode(s) [4] 41360 0
2200 - Bankstown
Recruitment postcode(s) [5] 41361 0
4029 - Herston
Recruitment postcode(s) [6] 41362 0
4108 - Coopers Plains
Recruitment postcode(s) [7] 41363 0
4102 - Woolloongabba
Recruitment postcode(s) [8] 41364 0
4020 - Redcliffe
Recruitment postcode(s) [9] 41365 0
3220 - Geelong
Recruitment postcode(s) [10] 41366 0
3000 - Melbourne
Recruitment postcode(s) [11] 41367 0
3065 - Fitzroy
Recruitment postcode(s) [12] 41368 0
3084 - Heidelberg
Recruitment postcode(s) [13] 41690 0
6000 - Perth
Recruitment postcode(s) [14] 41691 0
6008 - Subiaco

Funding & Sponsors
Funding source category [1] 314838 0
University
Name [1] 314838 0
NHMRC-NIHR Collaborative Research Grant
Country [1] 314838 0
Australia
Primary sponsor type
University
Name
Cardiff and Vale University
Address
Heath Park, Cardiff CF14 4XW, United Kingdom
Country
United Kingdom
Secondary sponsor category [1] 316834 0
University
Name [1] 316834 0
The University of Sydney NHMRC Clinical Trial Centre
Address [1] 316834 0
Level 6, 119-143 Missenden Rd, Camperdown NSW 2050
Country [1] 316834 0
Australia
Other collaborator category [1] 282814 0
University
Name [1] 282814 0
University of Leeds Clinical Trial Research Unit
Address [1] 282814 0
Leeds Institute of Clinical Trials Research, Level 10 Worsley Building, Clarendon Way, University of Leeds, Leeds LS2 9NL
Country [1] 282814 0
United Kingdom

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 313840 0
Sydney Local Health District Ethics Review Committee (RPAH Zone)
Ethics committee address [1] 313840 0
Ethics committee country [1] 313840 0
Australia
Date submitted for ethics approval [1] 313840 0
28/08/2023
Approval date [1] 313840 0
17/10/2023
Ethics approval number [1] 313840 0
2023/ETH00749

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 129514 0
Dr Kheng-Seong Ng
Address 129514 0
Royal Prince Alfred Hospital, Missenden Road, Camperdown NSW 2050
Country 129514 0
Australia
Phone 129514 0
+61 2 9767 9992
Fax 129514 0
Email 129514 0
[email protected]
Contact person for public queries
Name 129515 0
Ashley Douglas
Address 129515 0
NHMRC CTC, Level 6, 119-143 Missenden Rd, Camperdown NSW 2050
Country 129515 0
Australia
Phone 129515 0
+61 2 9562 5000
Fax 129515 0
+61 2 9565 1863
Email 129515 0
[email protected]
Contact person for scientific queries
Name 129516 0
Ashley Douglas
Address 129516 0
NHMRC CTC, Level 6, 119-143 Missenden Rd, Camperdown NSW 2050
Country 129516 0
Australia
Phone 129516 0
+61 2 9562 5000
Fax 129516 0
+61 2 9565 1863
Email 129516 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?
De-identified individual participant data datasets generated and/or analysed during the current study will be available upon request.
When will data be available (start and end dates)?
Data will be made available at the end of the trial. Data will remain available from then on for as long as the data is retained.
Available to whom?
Researchers
Available for what types of analyses?
Data will only be released for legitimate secondary research purposes, where the Chief Investigator, Sponsor and HREC agree that the proposed use has scientific value and will be carried out to a high standard and that there are resources available to satisfy the request.
How or where can data be obtained?
Requests for data should be sent to [email protected] to discuss and agree on suitable requirements for release.


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.