Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12622001251718
Ethics application status
Approved
Date submitted
12/09/2022
Date registered
19/09/2022
Date last updated
19/09/2022
Date data sharing statement initially provided
19/09/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
A study of treatment with Tadalifil in women with overactive bladder
Scientific title
Efficacy of tadalafil therapy in women with refractory idiopathic detrusor overactivity.
Secondary ID [1] 307930 0
Nil
Universal Trial Number (UTN)
Nil
Trial acronym
Nil
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Overactive bladder 327583 0
Condition category
Condition code
Renal and Urogenital 324670 324670 0 0
Other renal and urogenital disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
All participant will be given either Tadalafil or placebo and then have a one week washout and crossover to receive other treatment. This is a phase 2A study. Dose will be 10mg Tadalafil (oral capsule) for 6 weeks.

Arm 1 will receive Tadalafil 10mg daily for 6 weeks - then a 1 week washout then 6 weeks placebo

Arm 2 will recieve placebo for 6 weeks, then a one week washout and then Tadalafil for six weeks

Participants will be asked to complete a diary daily including symptoms and indicate they have taken medication. All medications unused should be returned to clinic so accountability can be conducted
Intervention code [1] 324390 0
Treatment: Drugs
Comparator / control treatment
Control will receive placebo and then crossover to active treatment. Placebo will consist of maize starch and pregelatinised maize starch, which is free from lactose and wheat allergens
Control group
Placebo

Outcomes
Primary outcome [1] 332499 0
A change in the number of incontinence episodes over the six weeks of active treatment assessed by a diary and counter that all participants will complete daily whilst enrolled on the study.
Timepoint [1] 332499 0
Six weeks of active treatment compared with six weeks of placebo
Primary outcome [2] 332500 0
A change in daytime frequency of urination assessed by a diary and counter that all participants will complete daily whilst enrolled on the study.
Timepoint [2] 332500 0
Six weeks of active treatment compared with six weeks of placebo
Primary outcome [3] 332501 0
A change in nightime frequency of urination assessed by a diary and counter that all participants will complete daily whilst enrolled on the study.
Timepoint [3] 332501 0
Six weeks of active treatment compared with six weeks of placebo
Secondary outcome [1] 413746 0
Quality of life of the participants assessed by the I-QOL ( Incontinence Quality of Life) questionnaire
Timepoint [1] 413746 0
Six weeks of active treatment compared to six weeks of placebo

Eligibility
Key inclusion criteria
Eligible patients are those with urodynamically proven idiopathic detrusor overactivity who have failed to respond significantly to all other medical treatments (including botulinum toxin injections) for their overactive bladder symptoms. Patients who had some benefit but intolerable side-effects from any of these treatments can also be enrolled.
Minimum age
18 Years
Maximum age
85 Years
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
• Age > 85 years
• Pregnancy, lactation
• Undiagnosed bleeding in patients with a uterus (use of PDE5 inhibitors in assisted reproduction can cause endometrial thickening)
• Unstable angina, uncontrolled hypotension <90/50
• Moderately severe cardiac failure or uncontrolled arrhythmias
• Myocardial or cerebral infarction within six months
• Concomitant use of nitrates
• Previous NAION – non-arteritic anterior ischaemic optic neuropathy
• Severe hepatic impairment
• End-stage renal disease
• Some medication and juices

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)
Central randomisation by computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created
by computer software (i.e. computerised sequence
generation)
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
Crossover
Other design features
Phase
Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
The magnitude of this placebo effect varies from study to study however there have been multiple systematic reviews and meta-analyses assessing outcomes from active and placebo arms (16-18). We have chosen to use this less heterogenous pooled data as the level for treatment and placebo effects. Based on this, a mean 25% improvement in incontinence episodes, daytime frequency and nocturia or 5 point improvement in I-QoL, will be regarded as a minimal clinical improvement. To support preliminary evidence of efficacy for tadalafil, we require 8 / 21 patients to demonstrate this level of improvement. To accommodate possible withdrawals from the study, 25 subjects will be enrolled (19-21).

16. Chapple C, Khullar V, Gabriel Z et al. The effects of antimuscarinic treatments in overactive bladder: an update of a systematic review and meta-analysis. Eur Urol 2008;54:543-562
17. Lee S, Malhotra B, Creanga D et al. A meta-analysis of the placebo response in antimuscarinic drug trials for overactive bladder. BMC Medical Research Methodology 2009,9:55
18. Herbison P, Hay-Smith J, Ellis G et al. Effectiveness of anticholinergic drugs compared with placebo in the treatment of overactive bladder: systematic review. BMJ 2003;326:19 Apr
19. Sambucini V. Comparison of single arm vs randomised phase II clinical trials: a Bayesian approach. J Biopharmaceutical Statistics 2015;25(3):474-489
20. Roychoudhury S, Scheuer N & Neuenschwander B. Beyond p-values: a phase ii dual-criterion design with statistical significance and clinical relevance.
21. Phadnis M. Sample size calculation for small sample singlearm trials for time to event data: logrank test with normal approximation or test statistic based on exact chi-square distribution. Contemp Clin Trials Commun 2019;15:100360

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/10/2022
Actual
Date of last participant enrolment
Anticipated
1/10/2023
Actual
Date of last data collection
Anticipated
31/12/2023
Actual
Sample size
Target
25
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 23150 0
Westmead Hospital - Westmead
Recruitment postcode(s) [1] 38508 0
2145 - Westmead

Funding & Sponsors
Funding source category [1] 312202 0
Government body
Name [1] 312202 0
Western Sydney Local Health District
Country [1] 312202 0
Australia
Primary sponsor type
Government body
Name
Western Sydney Local Health District
Address
Cnr Hawkesbury & Darcy Rd, Westmead NSW 2145
Country
Australia
Secondary sponsor category [1] 313728 0
Individual
Name [1] 313728 0
Dr Jennifer King
Address [1] 313728 0
Department of Urogynaecology Westmead Hospital
Cnr Hawkesbury & Darcy Rd,
Westmead NSW 2145
Country [1] 313728 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 311585 0
Western Sydney Local Health District Human Research Ethics Committee
Ethics committee address [1] 311585 0
WSLHD Research Office
Cnr Hawkesbury & Darcy Rd,
Westmead NSW 2145
Ethics committee country [1] 311585 0
Australia
Date submitted for ethics approval [1] 311585 0
16/06/2022
Approval date [1] 311585 0
23/08/2022
Ethics approval number [1] 311585 0
2022/PID01324 - 2022/ETH01170

Summary
Brief summary
This study will investigate the safety and efficacy of Tadalafil when given to women with an overactive bladder. We aim to investigate if women who receive this therapy have a decrease in urinary incontinence both during the day and night. All participants will receive six weeks of Tadalafil and six week of placebo in random order.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 121614 0
Dr Jennifer King
Address 121614 0
Department of Urogynaecology Westmead Hospital
Cnr Hawkesbury & Darcy Rd
Westmead NSW 2145
Country 121614 0
Australia
Phone 121614 0
+61 288907668
Fax 121614 0
+61 288907394
Email 121614 0
j.king@sydney.edu.au
Contact person for public queries
Name 121615 0
Dr Jennifer King
Address 121615 0
Department of Urogynaecology Westmead Hospital
Cnr Hawkesbury & Darcy Rd
Westmead NSW 2145
Country 121615 0
Australia
Phone 121615 0
+61 288907668
Fax 121615 0
+61 288907394
Email 121615 0
j.king@sydney.edu.au
Contact person for scientific queries
Name 121616 0
Dr Jennifer King
Address 121616 0
Department of Urogynaecology Westmead Hospital
Cnr Hawkesbury & Darcy Rd
Westmead NSW 2145
Country 121616 0
Australia
Phone 121616 0
+61 288907668
Fax 121616 0
+61 288907394
Email 121616 0
j.king@sydney.edu.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?
Raw line by line participant data collected during the study, including demographics and diary entry, questionnaires
When will data be available (start and end dates)?
Once study has concluded and been published anticipated 30/12/2023 for a period of 12 months till 30/12/2024
Available to whom?
Data will be made available to researcher who submit an ethically approved protocol and this will be assessed by the Principal investigator and the sponsor on a case by case basis
Available for what types of analyses?
IPD Meta analysis
How or where can data be obtained?
Please email the Principal Investigator j.king@sydney.edu.au


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
17112Ethical approval  j.king@sydney.edu.au 384639-(Uploaded-12-09-2022-17-05-19)-Study-related document.pdf



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.