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Trial registered on ANZCTR


Registration number
ACTRN12612000216819
Ethics application status
Approved
Date submitted
13/02/2012
Date registered
21/02/2012
Date last updated
21/02/2012
Type of registration
Retrospectively registered

Titles & IDs
Public title
Botulinum Toxin A (BTXA) versus Hydrodistension for Refractory Interstitial Cystitis/Painful Bladder Syndrome (IC/PBS)- a Multicentre, Prospective, Randomized, Double Blind Study
Scientific title
Botulinum Toxin A (BTXA) versus Hydrodistension for Refractory Interstitial Cystitis/Painful Bladder Syndrome (IC/PBS)- a Multicentre, Prospective, Randomized, Double Blind Study
Secondary ID [1] 279874 0
nil
Universal Trial Number (UTN)
U1111-1127-9192
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
interstitial cystitis/painful bladder syndrome 285778 0
Condition category
Condition code
Renal and Urogenital 285955 285955 0 0
Other renal and urogenital disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Injection of Botulinum A toxin; Dysport 500U diluted in 30 mls of saline and injected into the bladder wall, submucosally. It occurs once. Hydrodistension involves stretching the bladder with infusd saline using 120 cm of hydrostatic pressure for 4 minutes .
Intervention code [1] 284198 0
Treatment: Drugs
Intervention code [2] 284301 0
Treatment: Other
Comparator / control treatment
Injection of saline plus hydrodistension
Injection of Saline, 30 mls into the bladder wall, submucosally. It occurs once. Hydrodistension involves stretching the bladder with infusd saline using 120 cm of hydrostatic pressure for 4 minutes .
Control group
Placebo

Outcomes
Primary outcome [1] 286438 0
improvement in Oleary Sant scores problem and symptom. O'leary Sant scoring is a validated , well recognized measure of the impact upon a patient of Interstitial cystitis symptoms and problems that they experience
Timepoint [1] 286438 0
3 months
Secondary outcome [1] 295894 0
diary data. This data asseses patient maximum voided volume, patient averaged voided volume. Frequency of voiding during the day, frequency of voiding at night
Timepoint [1] 295894 0
3 months
Secondary outcome [2] 296030 0
patient global impression improvement. This is a standardised, validated questionnaire patients will complete
Timepoint [2] 296030 0
3 months
Secondary outcome [3] 296031 0
patient global impression severity. This is a standardised, validated questionnaire patients will complete
Timepoint [3] 296031 0
3 months
Secondary outcome [4] 296032 0
urodynamic data. This is a standardised test that will collect the following information; peak flow rate,voided volume, residual post void volume left in bladder, maximum filling capacity, bladder compliance (pressure rise in cm H20 for a volume of fluid instilled) . Incontinence if it occurs.
Timepoint [4] 296032 0
3 months
Secondary outcome [5] 296033 0
urge incontinence impact questionnaire data. This is a standardised, validated questionnaire patients will complete measuring specifically symptoms of urinary urgency
Timepoint [5] 296033 0
3 months

Eligibility
Key inclusion criteria
Female, chronic, refractory interstitial cystitis, painful bladder syndrome
Minimum age
18 Years
Maximum age
100 Years
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
urinary tract infection
pregnancy
systemic steroid use
cancer
voiding impairment

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)
enrolment ; existing patients from 3 specialist referral centres invited to participate. Urinary tract infection tested for.
Subjects were randomised to receive, under general anaesthetic, either a 4 minute hydrodistension with injection of 30 mls of normal saline into the bladder wall, or hydrodistension with injection of 500 Units of BTXA Dysport (registered trademark) diluted in 30 mls of normal saline. Both were injected through a 30 cm Bard 23 gauge needle at 30 sites in 1 ml aliquots, sparing the trigone and avoiding ureters. A bladder biopsy was obtained if not already available.

Urodynamic studies were repeated upon recruitment if not recently done. A free urinary flow rate with post void residual was performed at 1 week post treatment.
Approval for the study was obtained from the Research and Ethics Committees of all 3 hospitals. There was no public trial registry enrolment in 2003.
Subjects and treating doctors were blinded to treatment allocation, which was prepared in the hospital pharmacy according to a series of computer generated randomization numbers, held confidentially by pharmacy. Unlabelled drug was then delivered to theatre
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
randomization numbers-computer generated by statistician from Dept mathematics local university
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Blinding maintained when all allowed access to active treatment-Botulinum A toxin at 3 months
Phase
Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/01/2004
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
50
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment postcode(s) [1] 4940 0
2291
Recruitment postcode(s) [2] 4941 0
3189
Recruitment postcode(s) [3] 4942 0
2305
Recruitment postcode(s) [4] 4943 0
3800

Funding & Sponsors
Funding source category [1] 284642 0
Self funded/Unfunded
Name [1] 284642 0
Jane Manning
Country [1] 284642 0
Australia
Funding source category [2] 284643 0
Commercial sector/Industry
Name [2] 284643 0
Ibsen pharmaceuticals, Bard, and the Principal investigator
Country [2] 284643 0
Australia
Funding source category [3] 284644 0
Commercial sector/Industry
Name [3] 284644 0
Bard
Country [3] 284644 0
Australia
Funding source category [4] 284645 0
Self funded/Unfunded
Name [4] 284645 0
Jane Manning
Country [4] 284645 0
Australia
Primary sponsor type
Hospital
Name
John Hunter Hospital
Address
Lookout Road
New Lambton NSW 2305
Country
Australia
Secondary sponsor category [1] 283596 0
None
Name [1] 283596 0
Address [1] 283596 0
Country [1] 283596 0
Other collaborator category [1] 260511 0
Hospital
Name [1] 260511 0
Mercy Hospital
Address [1] 260511 0
Mercy Hospital for Women
63 Studley Road, Heidelberg 3084
Melbourne, Victoria
Country [1] 260511 0
Australia
Other collaborator category [2] 260512 0
Hospital
Name [2] 260512 0
Monash Medical Centre
Address [2] 260512 0
Monash Medical Centre
246 Clayton Road
Clayton 3168

Melbourne, Victoria
Country [2] 260512 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 286697 0
Hunter New England Area Research Ethics and Governance Unit
Ethics committee address [1] 286697 0
Locked Bag 1
New Lambton
NSW 2305
Ethics committee country [1] 286697 0
Australia
Date submitted for ethics approval [1] 286697 0
Approval date [1] 286697 0
01/01/2004
Ethics approval number [1] 286697 0
03/09/10/3.10

Summary
Brief summary
Background
IC/PBS requires effective treatment options.
Objective
Is BTXA effective for the treatment of IC/PBS?
Design, Setting and Participants:
2003-2009, 55 severe, refractory female subjects from 3 referral centres invited. UTI, malignancy, steroid use excluded.
Intervention
Double blind design, random allocation to treatment with hydrodistension and bladder wall injection of normal saline, or else hydrodistension with injection of BTXA.
Outcome measures and statistical Analysis
O’Leary Sant (OLS) problem (PI) and Symptom (SI), UIIQ, compared between BTXA and controls.
Repeated measures ANOVA tested whether BTXA subjects performed better than control subjects (group effect) for changes from baseline to 3 months (time effect) by assessing significance of group by time interaction. Multivariate modelling analyzed effect over time of other possible confounders. Measurements made beyond 3 months, but no further randomized comparisons possible, as majority subjects then chose active BTXA injection. Withdrawal; 4 subjects completed questionnaires too poorly, 1 withdrawn pre treatment with bladder cancer, leaving 50.

Results and limitations:
In both groups, the OLS, bladder diary, UIIQ scores showed improvement over 3 months. But no difference detected during initial analysis between the BTXA and control subjects for any outcome measure except OLS PI, where improvement noted at 3 months (P=0.04). 12 had UTI treated during the study. This significantly confounded, with greater improvement seen in the control group treated for UTI. Multivariate modelling accounted for effect of UTI showing improvement in the total OLS score (P=0.02), the OLS SI for the BTXA (P=0.008) group, pain (Q4 of OLS PI) (P=0.015) for the BTXA group at 3 months. 24% request continuing periodic BTXA treatment.
Conclusions
BTXA treatment improves OLS score at 3 months when compared to hydrodistension and saline injection alone, for a minority women. Consideration of the significant confounding effect of UTI, strengthened this improvement.
Trial website
Trial related presentations / publications
IUGA Lake Como 2009
Public notes

Contacts
Principal investigator
Name 33734 0
Address 33734 0
Country 33734 0
Phone 33734 0
Fax 33734 0
Email 33734 0
Contact person for public queries
Name 16981 0
Jane Manning
Address 16981 0
PO Box 648
The Junction 2291 NSW
Australia
Country 16981 0
Australia
Phone 16981 0
61 02 4940869
Fax 16981 0
61 02 49610599
Email 16981 0
[email protected]
Contact person for scientific queries
Name 7909 0
Jane Manning
Address 7909 0
PO Box 648
The Junction 2291 NSW
Australia
Country 7909 0
Australia
Phone 7909 0
61 02 4940869
Fax 7909 0
Email 7909 0
61 02 49610599

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