Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12613000285752
Ethics application status
Approved
Date submitted
25/02/2013
Date registered
11/03/2013
Date last updated
14/11/2018
Date data sharing statement initially provided
14/11/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Refractory Urge Incontinence in Women: a randomized placebo controlled trial of antibiotic therapy for cystitis erradication
Scientific title
Refractory Urge Incontinence in Women: a randomized placebo controlled trial of antibiotic therapy for cystitis erradication
Secondary ID [1] 282021 0
Nil Known
Universal Trial Number (UTN)
U1111-1139-8550
Trial acronym
To be determined
Linked study record

Health condition
Health condition(s) or problem(s) studied:
detrusor overactivity 288468 0
urge incontinence 288469 0
bacterial cystitis 288470 0
Condition category
Condition code
Renal and Urogenital 288815 288815 0 0
Other renal and urogenital disorders
Infection 288920 288920 0 0
Studies of infection and infectious agents

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Antibiotic therapy will be as follows:
Amoxycillin 500mg and clavulanic acid 125mg twice daily for 2 weeks, oral capsule
then Norfloxacin 400mg twice daily for 2 weeks oral capsule
then Nitrofurantoin 100mg four times daily or 2 weeks, oral capsule
Intervention code [1] 286611 0
Treatment: Other
Comparator / control treatment
Identical placebo tablets
Control group
Placebo

Outcomes
Primary outcome [1] 288958 0
The primary outcome measure will be the relative change in urge incontinence, measured on 24 hour pad test. Cure will be defined as <8mL on a 24 hour pad test
Timepoint [1] 288958 0
6 Months after randomization
Secondary outcome [1] 301440 0
The secondary outcome measure will be frequency of micturition on 3 day Bladder diary. Cure on 3 day bladder diary is defined as < 8 voids per day.
Timepoint [1] 301440 0
6 months after randomisation

Eligibility
Key inclusion criteria
Patients will be female, over 50 years of age who present with a main complaint of urge incontinence.
Urodynamic testing will show a primary diagnosis of detrusor overactivity (DO).
Patients will have failed to respond to bladder training with at least 2 anti-muscarinic therapeutic agents over 2 years.
Participants must leak urine at least 1 episode per 3 days on frequency volume chart.
Minimum age
50 Years
Maximum age
90 Years
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
a. Neuropathic DO (such as multiple sclerosis, spinal cord injury, Parkinsonism) b. Voiding dysfunction, defined as urinary flow rate less than 15 ml per sec for volume greater than 200ml with residual volume greater than 100ml c. Insufficient English language skills, or dementia, ie unable to complete questionnaires unaided. d. elevated creatinine, renal failure, e. allergy to more than penicillin

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)
All patients who meet inclusion and exclusion criteria, who give informed consent, will have a screening midstream urine culture and a 2 week wash out of previous anti-muscarinic drugs, then will be randomized to active treatment or placebo.

Allocation concealment procedure = Sealed opaque envelopes
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation will be dynamic (adaptive) random allocation methods. Patients will be randomised to the placebo or antibiotic group, using method minimisation stratified for severity of incontinence (based on 24 hour pad test, less than 75mL per 24 hours, equal to 75mL per 24 hours) and proven history of classical bacterial cystitis.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
None
Phase
Phase 4
Type of endpoint/s
Efficacy
Statistical methods / analysis
Previous studies suggest that approximately 20% of women would no longer suffer from severe urge incontinence (greater than 9 visits to the toilet per day) after 6 months of standard treatment. An increase of this rate to 35% with antibiotic treatment would provide sufficient activity. Based on the Simon’s 2 stage design, 80 patients receiving antibiotic treatment would have >80% power with 95% confidence to rule out an estimate of benefit of 20% in favour of a rate of 35%.

The primary outcome will be estimated as the proportion of patients experiencing a cure at 6 months post randomization together with 95% confidence intervals. Continuous variables will be described using mean and standard deviations; categorical variables will be summarized using percentages and time-to-event outcomes by the Kaplan-Meier method. Where exploratory analyses are performed these will be compared using t-tests or chi-squared tests as appropriate together with regression methods (logistic, proportional hazards) as required.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
1/06/2014
Actual
Date of last participant enrolment
Anticipated
1/02/2019
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
166
Accrual to date
0
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 677 0
St George Hospital - Kogarah
Recruitment hospital [2] 678 0
Wollongong Hospital - Wollongong
Recruitment postcode(s) [1] 6418 0
2217 - Kogarah
Recruitment postcode(s) [2] 6423 0
2500 - Wollongong

Funding & Sponsors
Funding source category [1] 286800 0
Government body
Name [1] 286800 0
National Health and Medical Research Council
Country [1] 286800 0
Australia
Funding source category [2] 289270 0
Charities/Societies/Foundations
Name [2] 289270 0
Bupa Health Foundation
Country [2] 289270 0
Australia
Primary sponsor type
University
Name
University of New South Wales
Address
University of New South Wales
Barker Street
Kensington New South Wales 2052
Country
Australia
Secondary sponsor category [1] 285590 0
University
Name [1] 285590 0
University of Wollongong,
Illawarra Health and Medical Research Institute, NSW
Address [1] 285590 0
University of Wollongong
Wollongong 2522

University of Wollongong
Northfileds Avenue
GWYNNEVILLE 2500
Country [1] 285590 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 288867 0
University of Wollongong/ ISLHD Health and Medical HREC
Ethics committee address [1] 288867 0
Ethics Unit, Research Services Office
University of Wollongong, NSW 2522, Australia
Ethics committee country [1] 288867 0
Australia
Date submitted for ethics approval [1] 288867 0
08/04/2013
Approval date [1] 288867 0
20/05/2014
Ethics approval number [1] 288867 0
CT13/003

Summary
Brief summary
Women with severe urgency of micturition and urge incontinence, who have not responded to treatment with bladder training and appropriate tablets for two years, will be invited to join a study whereby they will receive a highly effective tablet (darifenicin) as well as either 6 weeks of antibiotics, or 6 weeks of placebo. Followup of clinical outcome will occur over 6 months.
Trial website
nil
Trial related presentations / publications
Public notes
to be added

Contacts
Principal investigator
Name 38126 0
Prof Kate H. Moore
Address 38126 0
Level 1 Pitney Clinical Sciences Building
St George Hospital
Short Street
KOGARAH NSW 2217
Country 38126 0
Australia
Phone 38126 0
+61-2-91132054
Fax 38126 0
+61-2-91133951
Email 38126 0
k.moore@unsw.edu.au
Contact person for public queries
Name 38127 0
Ms Wendy Allen
Address 38127 0
Continence Research Nurse
Pelvic Floor Unit
St George Hospital
Cnr Belgrave & South Sts
KOGARAH NSW 2217
Country 38127 0
Australia
Phone 38127 0
+61-2-91132272
Fax 38127 0
+61-2-91133546
Email 38127 0
wendy.allen@sesiahs.health.nsw.gov.au
Contact person for scientific queries
Name 38128 0
Prof Kate H. Moore
Address 38128 0
Level 1 Pitney Clinical Sciences Building
St George Hospital
Short Street
KOGARAH NSW 2217
Country 38128 0
Australia
Phone 38128 0
+61-2-91132054
Fax 38128 0
+61-2-91133951
Email 38128 0
k.moore@unsw.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


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
SourceTitleYear of PublicationDOI
EmbaseBacterial colonization of bladder urothelial cells in women with refractory Detrusor Overactivity: The effects of antibiotic therapy.2021https://dx.doi.org/10.1093/femspd/ftab031
N.B. These documents automatically identified may not have been verified by the study sponsor.