Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12622000999730
Ethics application status
Approved
Date submitted
6/07/2022
Date registered
15/07/2022
Date last updated
10/05/2024
Date data sharing statement initially provided
15/07/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
Continence Achieved through Recording of Electrophysiology (CARE) Study: A Prospective Study to Evaluate the Safety and Feasibility of using the Closed Loop Medical Sacral Nerve Stimulation System in the treatment of symptoms of Overactive Bladder.
Scientific title
A Prospective Study to Evaluate the Safety and Feasibility of using the Closed Loop Medical Sacral Nerve Stimulation System in the treatment of symptoms of Overactive Bladder
Secondary ID [1] 307013 0
CLIN-PCL-008557
Universal Trial Number (UTN)
Trial acronym
CARE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Symptoms of Overactive Bladder (OAB) 326167 0
Condition category
Condition code
Renal and Urogenital 323476 323476 0 0
Other renal and urogenital disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The intervention in this trial consists of the implantation of and electronic active medical device, a sacral nerve stimulator, known as the Repose Sacral Nerve Stimulator with implantable leads, which is aimed to reduce symptoms of overactive bladder. The trial is done in 2 stages. During the first stage, leads are implanted near the sacral nerves and connected to an external trial stimulator for a duration of 14-30 days. The surgery in this stage takes about 1 hour and is performed under complete anaesthesia. If the system is deemed to appropriately reduce the symptoms of overactive bladder, a permanently implanted stimulator is implanted during a second stage procedure which takes about 1 hour under complete anaesthesia. Both procedures are performed by qualified urologists, urogynaecologists, gynaecologists, or similarly qualified investigators. Stimulation will commence after the participant has recovered from surgery. Stimulation parameters will be within ranges normally used for Sacral Nerve Stimulation (SNS), typically stimulating with charge-balanced pulses near an amplitude of 2mA, a pulse width of 210 us and a frequency of 14Hz.
The participants are followed up for a duration of 2 years with scheduled visits at 1, 3, 6, 9, 12, 18, and 24 months after the permanent implantation surgery. Prior to the scheduled visits, the study sites will call the participants to ensure compliance with the study requirements and investigate the need for troubleshooting. At the end of the trial, the participants can elect to keep their stimulator and will continue to receive standard care.
Intervention code [1] 323481 0
Treatment: Devices
Comparator / control treatment
No control treatment.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 331225 0
The incidence and severity of device or device procedure related Serious Adverse Events and Unexpected Adverse Device Effects when the device is in use; and All other possible device or device procedure related adverse events throughout the study duration including device deficiencies; and Detection of the electrophysiological components of the response to SNS will be captured by dichotomous choice (Yes/No).
Adverse events will be recorded by the investigator or site study personnel based on patient self-report or observations during visits. AEs are assessed and classified by the investigator and an independent medical monitor.
A complete list of known possible adverse events and their likelihood of occurrence is provided to participants in the Patient Information and Consent Form, these include Pain and/or discomfort including pelvic pain, Infection that may require hospitalisation with intravenous antibiotic therapy, and Abnormal sensations (e.g. numbness) or abnormal muscle control (e.g. weakness).
Timepoint [1] 331225 0
Baseline, end of test stimulation phase, and 1 month, 3, 6, 9, 12,18 and 24 months post permanent device implantation. Patient self-reported adverse events will be recorded at any point during the study when they arise.
Secondary outcome [1] 409234 0
Changes in overactive bladder (OAB) symptoms (voiding frequency) will be assessed by comparing the 3-day bladder diaries at baseline to those completed at each follow up visit post implant.
The bladder diaries are a standard format used in clinical practice. For this study we will provide the option to use a mobile application or a paper-based diary to log the voids
Timepoint [1] 409234 0
Baseline, end of test stimulation phase, and 1 month, 3, 6, 9, 12,18 and 24 months post permanent device implantation.
Secondary outcome [2] 409235 0
Effect of the therapy on faecal incontinence (voiding frequency) (if present) will be assessed using a 7-day diary.
Timepoint [2] 409235 0
Baseline, end of test stimulation phase, and 1 month, 3, 6, 9, 12,18 and 24 months post permanent device implantation.
Secondary outcome [3] 409236 0
Changes in lower urinary tract symptoms are assessed using the ICIQ-MLUTS questionnaire for males, and the ICIQ-FLUTS questionnaire for females.
Timepoint [3] 409236 0
Baseline, end of test stimulation phase, and 1 month, 3, 6, 9, 12,18 and 24 months post permanent device implantation.
Secondary outcome [4] 409237 0
Changes in participant-reported wellbeing assessed with the ICIQ-OABqol questionnaire.
Timepoint [4] 409237 0
Baseline, end of test stimulation phase, and 1 month, 3, 6, 9, 12,18 and 24 months post permanent device implantation.
Secondary outcome [5] 409953 0
Changes in participant’s sexual function (optional) using a 7-item sexual function questionnaire for females and a 5-item sexual function questionnaire for males. The questionnaires have been designed specifically for this study.
Timepoint [5] 409953 0
Baseline, end of test stimulation phase, and 1 month, 3, 6, 9, 12,18 and 24 months post permanent device implantation.
Secondary outcome [6] 409954 0
Patient global impression of improvement assessed with a PGI-I questionnaire.
Timepoint [6] 409954 0
Baseline, end of test stimulation phase, and 1 month, 3, 6, 9, 12,18 and 24 months post permanent device implantation.
Secondary outcome [7] 409955 0
Usability of the system is assessed using a short questionnaire (optional). The questionnaires have been designed specifically for this study.
Timepoint [7] 409955 0
Baseline, end of test stimulation phase, and 1 month, 3, 6, 9, 12,18 and 24 months post permanent device implantation.
Secondary outcome [8] 411592 0
Assess feasibility of applying closed-loop control using device data logs.
Timepoint [8] 411592 0
Baseline, end of test stimulation phase, and 1 month, 3, 6, 9, 12,18 and 24 months post permanent device implantation.
Secondary outcome [9] 411751 0
Changes in OAB symptoms (voiding control) will be assessed by comparing the 3-day bladder diaries at baseline to those completed at each follow up visit post implant.
Timepoint [9] 411751 0
Baseline, end of test stimulation phase, and 1 month, 3, 6, 9, 12,18 and 24 months post permanent device implantation.
Secondary outcome [10] 411753 0
Effect of the therapy on faecal incontinence (voiding control) (if present) will be assessed using a 7-day diary.
Timepoint [10] 411753 0
Baseline, end of test stimulation phase, and 1 month, 3, 6, 9, 12,18 and 24 months post permanent device implantation.
Secondary outcome [11] 411755 0
Changes in participant-reported wellbeing assessed with the EQ-5D-5L questionnaire.
Timepoint [11] 411755 0
Baseline, end of test stimulation phase, and 1 month, 3, 6, 9, 12,18 and 24 months post permanent device implantation.
Secondary outcome [12] 411757 0
Patient satisfaction assessed with a 5-point Likert Scale.
Timepoint [12] 411757 0
Baseline, end of test stimulation phase, and 1 month, 3, 6, 9, 12,18 and 24 months post permanent device implantation.
Secondary outcome [13] 411758 0
Patient global impression of improvement assessed with a CGI-I questionnaire.
Timepoint [13] 411758 0
Baseline, end of test stimulation phase, and 1 month, 3, 6, 9, 12,18 and 24 months post permanent device implantation.
Secondary outcome [14] 411759 0
Assess safety of applying closed loop control using adverse event reporting.
Adverse events (AE) will be recorded by the investigator or site study personnel based on patient self-report or observations during visits. AEs are assessed and classified by the investigator and an independent medical monitor. A complete list of known possible adverse events and their likelihood of occurrence is provided to participants in the Patient Information and Consent Form, these include Pain or discomfort due to undesirable stimulation sensation and/or location, and Abnormal sensations (e.g. numbness) or abnormal muscle control (e.g. weakness).
Timepoint [14] 411759 0
Baseline, end of test stimulation phase, and 1 month, 3, 6, 9, 12,18 and 24 months post permanent device implantation. Patient self-reported adverse events will be recorded at any point during the study when they arise.

Eligibility
Key inclusion criteria
Participants in this study must meet all of the following inclusion criteria, as determined by the Investigator:
1. Participant has a diagnosis of chronic OAB (> 12 months) and documented evidence from a 3-day bladder diary of 4 involuntary leaks associated with urgency during the 3-day period.
2. Participant has tried and failed one or more conservative therapies (e.g. drug therapy, diet/lifestyle modification, pelvic floor physiotherapy (including bladder re-training), biofeedback, osteopathy, acupuncture) and is suitable to proceed to more advanced therapies, as determined by the Investigator.
3. Participant has been approved by the Investigator to undergo an SNS procedure.
4. Participant is an appropriate candidate for the surgical procedures required in this study based on the clinical judgment of the Investigator.
5. Participant is on a stable dose (no new, discontinued, or changes in dose) of all medication to treat their OAB for at least 4 weeks prior to the implantation.
6. Participant is male or female, 18 years of age or older
7. Participant has residual bladder volume less than 150cc in Post-void Residual Volume Measurement test.
8. Participant is able and willing to comply with the protocol and follow-up.
9. Participant is fluent in the English language.
10. Participant is able to provide written informed consent.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Participants in this study must not meet any of the following exclusion criteria, as determined by the Investigator:
1. Participant has a primary diagnosis of stress incontinence (or mixed incontinence where the stress component overrides the urgency component)
2. Participant has a concomitant diagnosis of neurogenic bladder.
3. Participant has a concomitant diagnosis of interstitial cystitis or bladder pain syndrome.
4. Participant has a pain complaint that forms a major component of their symptomatology which, in the opinion of the investigator, may confound reporting of OAB symptoms.
5. Participant has a urinary tract obstruction or urethral stricture.
6. Participant has a history of pelvic radiation or ongoing pelvic cancer.
7. Participant has a medical condition that could interfere with study procedures, accurate bladder function reporting and/or confound evaluation of study endpoints, as determined by the Investigator.
8. Participant has evidence of an active disruptive psychological or psychiatric disorder or other known condition significant enough to impact perception of disease, compliance with intervention and/or ability to evaluate treatment outcomes.
9. Participant has a diagnosis of an uncontrolled coagulation disorder, bleeding diathesis, or progressive peripheral vascular disease.
10. Participant has a diagnosis of type I or type II diabetes requiring insulin therapy.
11. Participant has previously failed an SNS therapy trial or had a full SNS system implanted.
12. Participant has an implanted pacemaker and/or another active implanted medical device that may interfere with the Repose SNS system.
13. In the previous 9 months, the participant has been treated with botulinum toxin injection for their OAB symptoms.
14. In the previous 3 months, the participant has been treated with tibial nerve stimulation for their OAB symptoms.
15. Participant has a condition currently requiring or likely to require the use of MRI, or high output ultrasound.
16. Participant has a life expectancy of less than 2 years.
17. Participant has a symptomatic, active systemic infection or local infection including an active urinary tract infection (UTI), or has had more than three culture-proven UTI’s in the previous 12 months.
18. Participant is allergic or has shown hypersensitivity to ethylene oxide or any materials of the neurostimulation system which come in contact with the body.
19. Participant is pregnant or nursing (requires negative pregnancy test for women of childbearing potential). If female and sexually active, participant must be using a reliable form of birth control, be surgically sterile or be at least 2 years post-menopausal.
20. Within 6 months of enrolment, participant has had a significant untreated addiction to dependency-producing medications or has been a substance abuser (including alcohol and/or illicit drugs).
21. Participant is concomitantly participating in another clinical study, unless pre-approved by the Sponsor.
22. Participant is involved in an injury claim under current litigation in which relief of their OAB symptoms may be considered detrimental (i.e. secondary gains).

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
The following general statistical methods may be employed to assess the study data:
• Standard summary statistics may be used to summarise key study variables. Categorical variables may be summarised via incidence and percent. Continuous variables may be summarised via mean, median, standard deviation, and range. 95% confidence intervals may also be included with summary statistics as appropriate.
• Standard tests for significance in change from baseline may be employed, including two sample t-tests, chi-square tests and the normal approximation to the binomial two-sample z-test.
• In the event that planned parametric methods are found to be inappropriate based upon observed distributions of individual variables, appropriate non-parametric methods may be employed.
• Unless stated otherwise, statistical significance is defined as achieving a p-value less than 0.05.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
1/07/2022
Actual
16/08/2022
Date of last participant enrolment
Anticipated
28/06/2024
Actual
Date of last data collection
Anticipated
26/06/2026
Actual
Sample size
Target
25
Accrual to date
8
Final
Recruitment in Australia
Recruitment state(s)
NSW,SA
Recruitment hospital [1] 22306 0
Prince of Wales Hospital - Randwick
Recruitment hospital [2] 26527 0
Calvary North Adelaide Hospital - North Adelaide
Recruitment postcode(s) [1] 37468 0
2031 - Randwick
Recruitment postcode(s) [2] 42568 0
5006 - North Adelaide
Recruitment outside Australia
Country [1] 25103 0
Netherlands
State/province [1] 25103 0
Maastricht, Radboudumc, Zwolle
Country [2] 25719 0
Belgium
State/province [2] 25719 0
Ghent, Leuven

Funding & Sponsors
Funding source category [1] 311323 0
Commercial sector/Industry
Name [1] 311323 0
Closed Loop Medical Pty Ltd
Country [1] 311323 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Closed Loop Medical Pty Ltd
Address
Level 2/5 Eden Park Dr, Macquarie Park, NSW, 2113
Country
Australia
Secondary sponsor category [1] 312761 0
None
Name [1] 312761 0
Address [1] 312761 0
Country [1] 312761 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 310824 0
Bellberry Limited
Ethics committee address [1] 310824 0
Ethics committee country [1] 310824 0
Australia
Date submitted for ethics approval [1] 310824 0
Approval date [1] 310824 0
14/04/2022
Ethics approval number [1] 310824 0
2022-02-103
Ethics committee name [2] 315276 0
St Vincent's Hospital Melbourne Human Research Ethics Committee
Ethics committee address [2] 315276 0
Ethics committee country [2] 315276 0
Australia
Date submitted for ethics approval [2] 315276 0
06/09/2023
Approval date [2] 315276 0
21/11/2023
Ethics approval number [2] 315276 0
CHREC-F003
Ethics committee name [3] 315277 0
Maastricht UMC
Ethics committee address [3] 315277 0
Ethics committee country [3] 315277 0
Netherlands
Date submitted for ethics approval [3] 315277 0
01/06/2022
Approval date [3] 315277 0
07/10/2022
Ethics approval number [3] 315277 0
22.0022731
Ethics committee name [4] 315278 0
Federal Agency for Medicines and Health Products (FAMHP)
Ethics committee address [4] 315278 0
Ethics committee country [4] 315278 0
Belgium
Date submitted for ethics approval [4] 315278 0
07/03/2024
Approval date [4] 315278 0
20/03/2023
Ethics approval number [4] 315278 0
CIV-22-06-039826

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

Contacts
Principal investigator
Name 118994 0
Prof Thierry Vancaillie
Address 118994 0
Women’s Health & Research Institute of Australia
Oldaker Street
Sydney NSW 2000
Country 118994 0
Australia
Phone 118994 0
+61 1300 722 206
Fax 118994 0
Email 118994 0
[email protected]
Contact person for public queries
Name 118995 0
Dean Karantonis
Address 118995 0
Closed Loop Medical
Level 2/5 Eden Park Dr, Macquarie Park, NSW, 2113
Country 118995 0
Australia
Phone 118995 0
+61 2 84058700
Fax 118995 0
Email 118995 0
[email protected]
Contact person for scientific queries
Name 118996 0
Dean Karantonis
Address 118996 0
Closed Loop Medical
Level 2/5 Eden Park Dr, Macquarie Park, NSW, 2113
Country 118996 0
Australia
Phone 118996 0
+61 2 84058700
Fax 118996 0
Email 118996 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
The device under investigation by the trial sponsor is proprietary. Aggregated data will be the subject of publications at multiple timepoints of follow-up.


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.