ANZCTR - Registration

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Trial registered on ANZCTR

Registration number

ACTRN12617000788370

Ethics application status

Approved

Date submitted

14/02/2017

Date registered

30/05/2017

Date last updated

9/02/2023

Date data sharing statement initially provided

1/05/2019

Date results information initially provided

9/02/2023

Type of registration

Prospectively registered

Titles & IDs

Public title

Personalised pelvic floor Muscle Training for Urinary incontinence after Prostatectomy

Scientific title

Efficacy of a personalised pelvic floor Muscle Training program on Urinary incontinence after radical Prostatectomy: A randomised clinical trial with embedded physiological studies

Secondary ID [1]

None

Universal Trial Number (UTN)

U1111-1196-7696

Trial acronym

MaTchUP

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Post-prostatectomy incontinence

Urinary incontinence

Prostate Cancer

Condition category

Condition code

Physical Medicine / Rehabilitation

Physiotherapy

Cancer

Prostate

Renal and Urogenital

Other renal and urogenital disorders

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

(i) Urethral muscle training - comprehensive individualized program focused on training the striated muscles that pressurize the urethra. Exercise relies on the principles of motor skill training with trans-perineal ultrasound imaging for assessment (during voluntary contraction, coughing and a 60-s maximal contraction) and biofeedback. Training is based on assessment outcomes and commences with skill acquisition (training of optimal muscle recruitment patterns to increase urethral pressure). A key focus is the striated urethral sphincter, but with tailoring to include the other muscles, based on the assessment. Treatment is progressed using principles of exercise physiology according to a decision tool developed with the Clinical Advisory Committee. Based on the assessed needs and deficits of the patient, progression includes; training of sustained holding to enhance adaptation of striated muscles to provide ongoing maintenance of continence, training of ballistic efforts for episodes of increased bladder pressure (lifting, coughing, etc), skill development for functional training into broad range of activities including training with increasing bladder volumes, and high performance training for demanding tasks including strength training. Daily home exercise to practice tasks taught in each session is encouraged and monitored.

Participants in Urethral training group will attend up to 10 sessions of face-to-face pelvic floor muscle training supervised by a physiotherapist. The number of sessions will be determined by the need for further training at the discretion of the treating physiotherapist or when the participant meets the criteria for continence defined as no urine loss for 5 days and no urine loss on the 24 hour pad test. Each session will last approximately 30 minutes. Participants will attend a session 1-2 weeks prior to surgery. Participants will commence training before surgery. They will attend up to 9 sessions post-surgery, 1 week apart, commencing on catheter removal (~2 weeks post-surgery). Adherence to treatment (home-based exercises) will be recorded using a weekly diary which will be inspected by the physiotherapist at each face-to-face treatment session. Participants will be instructed to perform their home-based exercise program with frequency and intensity guided by their capacity. Home exercises will involve practice of the tasks provided by their physiotherapist at the previous visit based on individualized assessment. Adherence to exercise will be encouraged by the physiotherapist and formally recorded monthly with other outcome measures using an online questionnaire.

Intervention code [1]

Rehabilitation

Intervention code [2]

Treatment: Other

Comparator / control treatment

(ii) Conventional training program - training focused on muscles around the anus. This program is commonly offered in physiotherapy clinics and hospitals and will follows principles used in most previous clinical trials. Training commences with assessment of muscle activation which may include digital rectal examination or anal surface electromyography (EMG). Participants perform three maximal voluntary contractions held for up to 10 seconds in three positions (lying, sitting and standing) twice per day. Daily home exercise is encouraged and monitored. Training progresses by hold duration. Treatment is supervised by a physiotherapist using the same schedule as that described for the Urethral training program.

(iii) No training control group - Participants will be provided with an information sheet that includes description of pelvic floor muscle anatomy and brief instruction on how to perform pelvic floor muscle exercise (as is currently standard in many hospital settings). Participants will be requested to refrain from seeking additional treatment until the primary end point at 3 months. Any treatment sought by participants will be recorded. Participants in this group will not be guided to perform home exercises.

Control group

Active

Outcomes

Primary outcome [1]

Continence defined by the 24-hour pad weight test. Continence will be defined as a loss of <2g of urine.

Timepoint [1]

3 months post-operative.

Secondary outcome [1]

Health-related quality of life - measured using the 12-Item Short Form Survey (SF-12)

Timepoint [1]

Measured at baseline, then at weekly intervals from week of catheter removal until 3 months. The measure will be collected once more at 12 months.

Secondary outcome [2]

Symptomatology and “bothersomeness” of incontinence - measured by the International Continence Society Male Short Form Questionnaire

Timepoint [2]

Measured at baseline, then at weekly intervals from week of catheter removal until 3 months. After 3 months the measure will be collected monthly until 12 months.

Secondary outcome [3]

Continence-related costs – measured using an electronic diary of continence-related costs

Timepoint [3]

Measured at baseline, then at weekly intervals from week of catheter removal until 3 months. After 3 months the measure will be collected monthly until 12 months.

Secondary outcome [4]

24-hour pad weight test

Timepoint [4]

Measured at baseline, then at weekly intervals from week of catheter removal until 3 months. After 3 months the measure will be collected monthly until 12 months.

Secondary outcome [5]

Measures of neuro-muscular control of urethral pressure assessed by the ultrasound measures of activation of pelvic floor muscles during (i) voluntary contraction of pelvic floor muscles; (ii) cough; and (iii) sustained 60-s maximal contraction of pelvic floor muscles

Timepoint [5]

Baseline, the week of catheter removal after surgery, 6 weeks, 3 months and 12 months

Secondary outcome [6]

International Physical Activity Questionnaire (IPAQ) to assess physical activity over the period the 24 hour pad weight test is conducted.

Timepoint [6]

Measured at baseline, then at weekly intervals from week of catheter removal until 3 months. After 3 months the measure will be collected monthly until 12 months.

Secondary outcome [7]

EQ-5D-5L questionnaire to calculate Quality-Adjusted Life-Years for cost-effectiveness analysis.

Timepoint [7]

Measured at baseline, then at weekly intervals from week of catheter removal until 3 months. The measure will be collected once more at 12 months.

Secondary outcome [8]

Sexual function will be recorded to understand how it relates to the primary outcome (continence). Sexual function will be determined by asking participants "Are you currently able to achieve a full erection?".

Timepoint [8]

Measured at baseline, then at weekly intervals from week of catheter removal until 3 months. The measure will be collected once more at 12 months.

Secondary outcome [9]

Bowel function will be recorded to understand how it relates to the primary outcome (continence). Bowel function will be determined by asking a series of questions previously described in a clinical trial of post-prostatcetomy incontinence:
1 - How often do you lose control of or leak stool? (Never, Occasionally, Some of the time, Most of the time, All of the time)
2 - If you do, how much does this bother you? (Between 0 - Not at all to 10 - A great deal)
3 - When you feel the need to open your bowels, do you have to rush urgently to the toilet? (Never, Occasionally, Some of the time, Most of the time, All of the time)
4 - When you have to rush urgently, do you ever lose control of or leak stool? (Never, Occasionally, Some of the time, Most of the time, All of the time)
5 - Did you ever lose control of or leak stool BEFORE your prostate surgery? (Yes/No)
6 - Do you have any of these other bowel problems? ([Tick box] Ulcerative colitis, Crohn’s disease, Irritable bowel syndrome, Constipation)

Timepoint [9]

Measured at baseline, then at weekly intervals from week of catheter removal until 3 months. The measure will be collected once more at 12 months.

Secondary outcome [10]

Treatment adherence will be will be recorded to understand how it relates to the primary outcome (continence). A study-specific online questionnaire will be used with the following questions:

In the past week, approximately how many days did you do your pelvic floor muscle exercises?

On a typical day in this past week that you did pelvic floor exercises, how many pelvic muscle contractions did you do?

During the past month, approximately how many days did you do your pelvic-floor muscle exercises?

On a typical day in this past month that you did pelvic floor exercises, how many pelvic muscle contractions did you do?

Was it hard to find the time to do all of the exercises? (Yes / No / Unsure)

Were you unsure if you were doing the exercises correctly? (Yes / No / Unsure)

Did the exercises cause any pain? (Yes / No / Unsure)

Did you have trouble remembering to do the exercises? (Yes / No / Unsure)

Did it seem as if the exercises were not helping your incontinence? (Yes / No / Unsure)

Were you so much better that you felt that you did not need to continue the exercises? (Yes / No / Unsure)

Are there any other reasons why you did not do the exercises? (Yes / No )

Did you contract your pelvic floor muscles to prevent urine from leaking when you performed a functional activity or coughed? (Yes / No / Unsure)

Timepoint [10]

Starting at the week of catheter removal and continuing monthly until 12 months.

Eligibility

Key inclusion criteria

Men scheduled to undergo radical prostatectomy (open or robotic) for prostate cancer. Men will be included if they are able to attend assessment and rehabilitation sessions and are able to understand English.

Minimum age

30 Years

Maximum age

70 Years

Sex

Males

Can healthy volunteers participate?

Key exclusion criteria

Main exclusion criteria are: (i) urinary incontinence prior to surgery; (ii) previous prostate or urethral surgery, (iii) assessment/training of pelvic floor muscles in preceding 6 months, (iv) scheduled to undergo or had previously undergone radiation therapy for prostate cancer.

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)

Randomisation will be in permuted blocks, stratified by surgeon and baseline neuro-muscular control of urethral pressure (patients dichotomised as good [or poor] by ability to achieve both greater than or equal to 4.1 mm dorsal displacement of the mid-urethra (striated urethral sphincter) and greater than or equal to 2.4 mm of urethro-vesical junction elevation (puborectalis). Different physiotherapists will provide the two training programs. Group allocation will be determined using an automatic randomisation schedule developed by an independent statistician and integrated into the REDCap data administration system (see below) to ensure concealed allocation. Assessors and statisticians will be blinded to group allocation. It will not be possible to blind the participant or treating therapist to the treatment, but patients will be blinded to the hypotheses.

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

Masking / blinding

Blinded (masking used)

Who is / are masked / blinded?

The people assessing the outcomes
The people analysing the results/data

Intervention assignment

Parallel

Other design features

Phase

Not Applicable

Type of endpoint/s

Efficacy

Statistical methods / analysis

Primary outcome is the proportion of participant’s continent at 3 months. This was selected as, qualitative research highlights that rapid/complete recovery of continence is a priority for men, and it was considered unethical to withhold treatment from men allocated to No training for more than 3 months if they continue to experience incontinence. This study is powered to determine whether the Urethral training is more efficacious than Conventional and No training, and whether this effect is moderated by baseline neuromuscular (NM )control of urethral pressure. Data from seven RCTs indicate ~60% of men receiving Conventional training will be incontinent at 3 months. Our data of healthy men suggest 55% have “good” NM control at baseline. We make the assumption that among those with good NM control at baseline, incontinence outcomes at 3 months will be similar regardless of their treatment assignment. Using the estimate of reduction of incontinence by a third to 40% of men at 3 months (based on the difference identified in previous study, which included some features we consider critical in the proposed program), with 80% power and two-sided significance level of 0.05 we need 97 men per group. With this number of participants we have 88% power to detect a significant interaction between baseline NM control and treatment arm if we assume that 30% men with good NM control at baseline will be incontinent at 3 months regardless of treatment, but that, of the men with poor NM control at baseline, 90% and 50% will be continent with urethral or conventional training, respectively. We will recruit 121 men per arm (adjusting for a potential drop-out rate of 20%).
Statistical analysis: A biostatistician will analyse blinded data, with all patients enrolled and randomised to treatment/no treatment arms comprising the data set for analysis. Baseline characteristics of groups will be tabulated using summary statistics. Multiple imputation will be used to account for missing data, with missing data imputed using logistic regression models for binary outcomes and predictive mean matching for continuous outcomes.
Primary analysis: For the continence outcome, a hierarchical logistic regression model including random effects to account for multiple measurements per participant, and random effects for surgeon, will be fit. This model will include a three-way interaction term between time, randomised treatment group, and baseline NM control, and all two-way interactions and main effects, as well as the stratifying variable of site. For the primary hypothesis, this model will be interrogated to yield differences in the proportions of participants recovering continence at 3 months between the groups and 95% confidence intervals. The model will be similarly interrogated to determine whether the effect of urethral training relative to conventional training is moderated by NM control of urethral pressure at baseline. Post-operative NM control measures will be considered in a secondary analysis.
Secondary analyses: The continuous measure of continence (24-hour pad test weight) and other continuous outcomes (ICS-male short, SF12) will be compared between groups by fitting a similar random effects linear regression model. Time to recovery of continence will be compared between groups using a Cox proportional hazards model using weekly 24-hr pad test. Model assumptions (linearity, normality and homoscedasticity of residuals for the linear regression models) and the Cox proportional hazards assumption will be assessed using standard diagnostic plots.
Mediation analysis: To determine the extent to which the effect of urethral training program on the primary outcome and on the continuous measurement of continence is mediated through an improvement in NM control, as hypothesised, we will apply a causal mediation analysis. Mediation analyses will be conducted for the NM control measure recorded at week 6 and month 3, with all analyses adjusted for baseline levels of NM control and other potential confounders of the outcome-mediator relationship. The analysis will be conducted in two stages: at the first stage, the effect of randomisation to the study arms on NM control measures will be assessed. Those measures that differ between groups will then be carried forward to the second stage of the analysis. In this second stage, models will be fit to estimate the direct effect of randomised group on outcome and the indirect effect of randomised group on the outcome that acts through the putative mediator. Whether the indirect effect of treatment on the outcomes changes depending on the level of NM control achieved after surgery will be investigated through the inclusion of interaction terms between treatment group and post-surgery NM control variables in the mediation analyses.
If significant mediation is found, logistic regression will be undertaken using the 3 month data of the NM control variables to determine which variables are best linked with continence. A factor analysis across all participants will be applied to extract common NM control features from the NM control variables. NM control features are then used as predictor variables in the logistic regression analysis to assess the relative contribution of each to the odds of regaining continence. This analysis would enable generation of an equation that predicts the probability of continence given the level of the measured NM control features, and therefore the amount of change that is required in individual features of NM control to achieve continence. This equation would have high clinical utility for targeting/prioritisation of treatment.
Cost effectiveness analysis: Costs of services and devices will be estimated using market prices. We will undertake two analyses at 3 and 12 months. First we will compare cost effectiveness between trial arms. Second we will address the question of whether treatment is more cost effective if only offered to men with poor NM control at baseline. For this analysis we will test the interaction between treatment arm and baseline NM control. This will test the hypothesis that continence-related costs will be similar for men with good NM control, regardless of treatment allocation, but costs will be significantly less for men with poor baseline NM control allocated to Urethral training. Quality-adjusted life-years saved (QALYs) will be computed using the EQ-5D-5L data collected from the trial. Cost-effectiveness ratios will be computed and n-way sensitivity analyses will be conducted to produce cost effectiveness acceptability curves for relevant sets of assumptions about costs and outcomes.

Recruitment

Recruitment status

Active, not recruiting

Date of first participant enrolment

Anticipated

1/06/2018

Actual

27/07/2018

Date of last participant enrolment

Anticipated

1/07/2021

Actual

22/12/2022

Date of last data collection

Anticipated

22/12/2023

Actual

Sample size

Target

363

Accrual to date

Final

133

Recruitment in Australia

Recruitment state(s)

QLD

Recruitment hospital [1]

Princess Alexandra Hospital - Woolloongabba

Recruitment hospital [2]

The Wesley Hospital - Auchenflower

Recruitment postcode(s) [1]

4102 - Woolloongabba

Recruitment postcode(s) [2]

4066 - Auchenflower

Funding & Sponsors

Funding source category [1]

Government body

Name [1]

Queensland Health

Address [1]

Queensland Health Building
147-163 Charlotte Street
Brisbane Queensland 4000 Australia

Country [1]

Australia

Funding source category [2]

Government body

Name [2]

National Health and Medical Research Council of Australia

Address [2]

16 Marcus Clarke St, Canberra ACT 2601

Country [2]

Australia

Primary sponsor type

University

Name

The University of Queensland

Address

Therapies Building 84A
The University of Queensland
St Lucia, Queensland
4072

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

University of Queensland Human Research Ethics Committee

Ethics committee address [1]

Research Management Office
Cumbrae-Stewart (Building 72)
The University of Queensland
St Lucia, Queensland,, 4072
AUSTRALIA

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

15/06/2017

Approval date [1]

08/11/2017

Ethics approval number [1]

2017001736

Ethics committee name [2]

Uniting Care Health Human Research Ethics Committee

Ethics committee address [2]

The Wesley Hospital
PO Box 499
Auchenflower Qld 4066
AUSTRALIA

Ethics committee country [2]

Australia

Date submitted for ethics approval [2]

15/06/2017

Approval date [2]

07/11/2017

Ethics approval number [2]

UnitingCare HREC 1739

Ethics committee name [3]

Metro South Human Research Ethics Committee

Ethics committee address [3]

Princess Alexandra Hospital Centres for Health Research
Level 7, Translational Research Institute
37 Kent Street
Woolloongabba QLD 4102
AUSTRALIA

Ethics committee country [3]

Australia

Date submitted for ethics approval [3]

15/06/2017

Approval date [3]

28/11/2017

Ethics approval number [3]

HREC/17/QPAH/591

Summary

Brief summary

The aim of this study is to evaluate efficacy of a personalised pelvic floor muscle training program on urinary incontinence after radical prostatectomy.

Who is it for?
Individuals may be eligible to join this study if you aged 30-70 years and are scheduled to undergo radical prostatectomy (open or robotic) for prostate cancer.

Study details
Study participants will be allocated by chance to one of the three groups, Urethral muscle training, Conventional training or No training. Urethral muscle training will involve an individualised program of pelvic floor muscle training that relies on the principles of motor skill training of the striated muscles that control urethral pressure with ultrasound imaging used for assessment and biofeedback. Participants in both treatment groups will attend up to 10 sessions of pelvic floor muscle training supervised by a physiotherapist, and participants in the No treatment group will not receive treatment. Participants in the treatment groups will attend a session 1-2 weeks prior to surgery and will commence training before surgery. They will attend up to 9 sessions post-surgery, 1 week apart, commencing on catheter removal (~2 weeks post-surgery).

This study will provide new insight into whether individualised pelvic floor muscle training is more effective than current treatments or no treatment for management of post-prostatectomy incontinence.

Trial website

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Prof Paul Hodges

Address

Therapies Building 84A
The University of Queensland
St Lucia, Queensland
4072

Country

Australia

Phone

+61 7 3365 2008

Fax

[email protected]

Contact person for public queries

Name

Dr Ryan Stafford

Address

Therapies Building 84A
The University of Queensland
St Lucia, Queensland
4072

Country

Australia

Phone

+61 432712145

Fax

[email protected]

Contact person for scientific queries

Name

Dr Ryan Stafford

Address

Therapies Building 84A
The University of Queensland
St Lucia, Queensland
4072

Country

Australia

Phone

+61 7 3346 7751

Fax

[email protected]

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

No/undecided IPD sharing reason/comment

Requests for data sharing will be considered on a case by case basis.

What supporting documents are/will be available?

Doc. No.	Type	Citation	Link	Email	Other Details	Attachment
41	Study protocol				Study protocol is now in press at BMJ Open.

Results publications and other study-related documents

Documents added manually

No documents have been uploaded by study researchers.

Documents added automatically

Source	Title	Year of Publication	DOI
Embase	Efficacy of a personalised pelvic floor muscle training programme on urinary incontinence after radical prostatectomy (MaTchUP): Protocol for a randomised controlled trial.	2019	https://dx.doi.org/10.1136/bmjopen-2018-028288

N.B. These documents automatically identified may not have been verified by the study sponsor.

Trial Review

Documents added manually

Documents added automatically