Administrative information
Title {1} | Proper Understanding of Recurrent Stress Urinary Incontinence Treatment in women (PURSUIT): A Randomised Controlled Trial of Endoscopic and Surgical Treatment. |
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Trial registration {2a and 2b}. | ISRCTN registry, ID: ISRCTN12201059. Registered on 09 January 2020. |
Protocol version {3} | Version 4.0, 03 September 2020 |
Funding {4} | This research is funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment (HTA) programme (project number 17/95/03). |
Author details {5a} | 1 Department of Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK. 2 Bristol Urological Institute, Southmead Hospital, North Bristol NHS Trust, Bristol, UK. 3 Department of Urogynaecology, Sheffield Teaching Hospitals NHS Foundation Trust, Jessop Wing, Tree Root Walk, Sheffield, UK. 4 Department of Urogynaecology, Birmingham Women’s & Children's Hospital NHS Foundation Trust, Birmingham, UK. 5 Department of Urology, University College London Hospital, London, UK. 6 Department of Urology, Cambridge University Hospitals NHS Trust, Cambridge, UK. 7 Department of Obstetrics and Gynaecology, NHS Ayrshire and Arran, University Hospital Crosshouse, Kilmarnock, UK. 8 Patient and Public Involvement (PPI) Representative, Bristol, UK. 9 Bristol Trials Centre (BTC), University of Bristol, Bristol, UK. 10 Department of Translational Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK. *Corresponding author |
Name and contact information for the trial sponsor {5b} | This trial is sponsored by Research and Innovation, North Bristol NHS Trust, Floor 3 Learning and Research Building, Southmead Hospital, Westbury-on-Trym, Bristol, BS10 5NB. Telephone: 0117 414 9330. Email: researchsponsor@nbt.nhs.uk. |
Role of sponsor {5c} | The PURSUIT study was designed in response to the HTA funding call 17/95 - Treatments for women with recurrent stress urinary incontinence after failed primary surgery. North Bristol NHS Trust was involved with the design of the study, preparation and approval of the study protocol and signing off the validation of the study database for data collection. The sponsor will ensure interim and final analysis of the data is conducted and will review and contribute to manuscripts for publication. |
Introduction
Background and rationale {6a}
Objectives {7}
Trial design {8}
Internal pilot
Nested studies
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Phase I: Understanding the recruitment process and how it operates at clinical sites. A multi-faceted approach will be used to investigate site-specific or wider recruitment obstacles.
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Phase II: Development and implementation of recruitment intervention strategies. The QRI team, with the CI and TMG, will formulate a ‘plan of action’ to improve recruitment and information provision, based on the findings from phase I.
Methods: participants, interventions and outcomes
Study setting {9}
Eligibility criteria {10}
Subject population
Inclusion criteria
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Adult women (≥18 years) with bothersome SUI symptoms after primary SUI surgery (including bulking injections)
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Urodynamics to confirm recurrent or persistent SUI
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Patient willing to consider interventional therapy
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Patient willing to be randomised and willing to give consent
Exclusion criteria
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Predominant urgency incontinence
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Pelvic organ prolapse (POP) more than or equal to stage II
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Relevant neurological disease, disease, such as a stroke, multiple sclerosis, Parkinson’s disease, or spina bifida (diabetes mellitus is not an exclusion criterion unless it is causing diabetic neuropathy)
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Being treated for gynaecological or bladder cancer
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Unresolved mesh exposure from previous MUT
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Current pregnancy
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Urethral diverticulum
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Recent pelvic surgery (for example, POP repair, stress incontinence surgery and hysterectomy within the last 6 months)
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Participation in another study that might influence results or increase patient burden
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Unable to give informed consent/complete assessments
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Previous artificial urinary sphincter surgery
Site selection
Delivery of interventions
Who will take informed consent? {26a}
Pre-screening and eligibility
Invitation to participate
Informed consent
Additional consent provisions for collection and use of participant data and biological specimens {26b}
Interventions
Explanation for the choice of comparators {6b}
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Autologous fascial sling: a strip of the patient’s own tissue (fascia) is used to compress the urethra.
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Colposuspension: the anterior vaginal wall is repositioned to support the urethra.
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Artificial urinary sphincter: an implanted cuff is used to compress the urethra to keep the woman continent. The compression can be released by pressing on a component in the vaginal labium so the woman can pass urine when she wants to.
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Endoscopic bulking injections: a cystoscope is used to guide injection of bulking agents to the urethra, to enhance its ability to close effectively.
Intervention description {11a}
Assessment procedure
Surgical treatment arm
Endoscopic (bulking injections) treatment arm
Criteria for discontinuing or modifying allocated interventions {11b}
Strategies to improve adherence to interventions {11c}
Relevant concomitant care permitted or prohibited during the trial {11d}
Provisions for post-trial care {30}
Outcomes {12}
Primary outcome measure
Secondary outcome measures
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Longer term clinical subjective measure of continence at 6 months and 2 and 3 years post randomisation (ICIQ-UI-SF)
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Improvement of symptoms post-intervention at 1, 2 and 3 years post randomisation (Patient Global Impression of Improvement (PGI-I) questionnaire)
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Procedure/operative assessment measures collected at the time of intervention and at 6 months post intervention: procedure/operation time, estimated blood loss, hospital stay, return to normal activity
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Assessment of sexual health at 1, 2 and 3 years post randomisation (Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire-IUGA Revised (PISQ-IR))
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The safety of each intervention (adverse events, AE) and the likelihood of re-treatment assessed at intervention, 6 months post intervention and 6 months and 1, 2 and 3 years post randomisation
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Cost-effectiveness from NHS and societal perspectives at 1 year post randomisation in terms of quality-adjusted life years (QALYs) and ICIQ-UI-SF at 1 year, and from a secondary care perspective in terms of QALYs at 3 years post randomisation. QALYs to be calculated from the EuroQol 5-Dimension 5-Level (EQ-5D-5L). Secondary care resource use to be abstracted from Trust electronic systems (or HES) at 1 and 3 years post randomisation, other resource use to be collected by questionnaires at 6 months and 1year post randomisation.
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Patient experiences of the intervention at 6 months and 1 year and 3 years post intervention (qualitative interviews with patients)
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Clinician views of the intervention at, or around, baseline (qualitative interviews with clinicians)
Participant timeline {13}
Pre-baseline | Baseline | Treatment | Post-treatment | Post-randomisation | |||||||
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3–6 months | 6 months | 1 year | 3 years | 6 months | 1 year | 2 years | 3 years | ||||
Pre-screening and eligibility | X | ||||||||||
Informed consent | X | ||||||||||
Randomisation | X | ||||||||||
Interventions | X | ||||||||||
Data collected by site staff | |||||||||||
- Case report forms | X | X | X | X | X | X | X | ||||
- Adverse events | X | X | X | X | X | X | |||||
Participant Questionnaires | |||||||||||
- ICIQ-UI-SF | X | X | X | X | X | ||||||
- PISQ-IR | X | X | X | X | |||||||
- EQ-5D-5L | X | X | X | X | X | ||||||
- PGI-I | X | X | X | ||||||||
- Non secondary care resource use | X | X | |||||||||
Secondary care resource use | X | X | |||||||||
Interview Study | |||||||||||
- Qualitative interview (patients) | X | X | X | X | |||||||
- Qualitative interview (staff) | X |
Sample size {14}
Recruitment {15}
Sequence generation {16a}
Concealment mechanism {16b}
Implementation {16c}
Randomisation
Assignment of interventions: blinding
Who will be blinded {17a}
Procedure for unblinding if needed {17b}
Data collection and management
Plans for assessment and collection of outcomes {18a}
Validated participant questionnaires
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International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI-SF) [19]. The questionnaire is used for evaluating the frequency, severity and impact on QoL of urinary incontinence in men and women across the world. It is also used to screen for incontinence, to obtain a brief yet comprehensive summary of the level, impact and perceived cause of symptoms of incontinence and to facilitate patient-clinician discussions.
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Pelvic Organ Prolapse (POP)/Urinary Incontinence Sexual Questionnaire, IUGA-Revised (PISQ-IR) [20]. This validated evaluation tool is used to assess sexual function in women with pelvic floor disorders.
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EuroQol Group’s 5-dimension health status questionnaire EQ-5D-5L [21]. A standardised instrument to measure generic health and the resulting profile is used to calculate QALYs.
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Patient Global Impression of Improvement (PGI-I) has been validated for use in females with urinary incontinence [22].
Case report forms (CRFs)
Baseline
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Patient contact details, including email address
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NHS/CHI number
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Patient demographics, including date of birth and ethnicity
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GP contact details
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Charlson Comorbidity Index data
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Record of other diagnostic assessments (e.g. flow rate test/urodynamics/cystoscopy)
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Current medications (including whether on topical oestrogen therapy)
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Parity
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Previous pelvic surgery and dates
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Anticipated cause of SUI (hypermobility/intrinsic sphincter deficiency/both/not diagnosed)
Time of treatment
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Date of admission
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Height, weight, and body mass index (BMI)
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American Society of Anaesthesiologists (ASA) physical status classification
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Date of procedure (if different from admission)
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Hospital where procedure took place
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Name of surgeon
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Treatment/Operative procedures
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◦ Endoscopic arm: type of urethral bulking agent(s) used
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Complications
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Details of catheterisation
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Transfusion
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Post void residual volume (PVR)
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Adverse events
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Date of discharge
Six months after treatment
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Adverse events
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Endoscopic arm only: re-intervention (i.e. was a repeat injection needed?)
Six months and 1 year, 2 years and 3 years after randomisation
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Complications of treatment (if applicable)
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Details of catheterisation (status/duration/other details)
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Have any other treatment procedures (interventions) taken place since initial treatment? If so, relevant (what/when) details of what and when.
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Adverse events
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Endoscopic arm only: re-intervention (i.e. was a repeat injection needed?)
Health economic data collection
Qualitative data collection
Recruitment Study phase I—understanding recruitment
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Members of the TMG, including the Chief Investigator (CI) and those involved in the design, management and leadership of the trial.
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Clinicians or researchers who are involved in the patient pathway and trial recruitment (at four pilot sites only).
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If necessary, eligible women who have been approached to take part in the trial (at four pilot sites only).
Recruitment Study phase II—development and implementation of recruitment intervention strategies
Interview Study
Plans to promote participant retention and complete follow-up {18b}
Data management {19}
Source data and documentation
Database platforms
Data storage and handling
Access to data
QRI and Interview Study data
Archiving and destruction of trial materials
Confidentiality {27}
Plans for collection, laboratory evaluation and storage of biological specimens for genetic or molecular analysis in this trial/future use {33}
Statistical methods
Statistical methods for primary and secondary outcomes {20a}
Summary of baseline data and flow of participants
Primary outcome analysis
Secondary outcome analysis
Interim analyses {21b}
Methods for additional analyses (e.g. subgroup analyses) {20b}
Subgroup analyses
Adjusted analysis
Health economic evaluation
QRI data analysis
Interview Study analysis
Methods in analysis to handle protocol non-adherence and any statistical methods to handle missing data {20c}
Plans to give access to the full protocol, participant-level data and statistical code {31c}
Oversight and monitoring
Composition of the coordinating centre and trial steering committee {5d}
Coordinating centre
Trial Management Group (TMG)
Trial Steering Committee (TSC)
Composition of the data monitoring committee, its role and reporting structure {21a}
Adverse event reporting and harms {22}
Adverse event (AE)
Serious adverse event (SAE)
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Results in death
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Is life-threatening
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Requires inpatient hospitalisation or prolongation of existing hospitalisation
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Results in persistent or significant disability or incapacity
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Consists of a congenital anomaly or birth defect.
Expected events
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Anaesthetic complications, e.g. stroke or cardiac events such as myocardial infarction
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Operative injury to adjacent structure
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Fistula
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Return to theatre
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ITU admission
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New urinary tract symptoms
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Urinary tract infection
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Wound infection
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Pelvic organ prolapse (POP)
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Urinary retention/catheterisation (intermittent self-catherisation (ISC) and indwelling)
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Pain
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Implant exposure (tape, AUS)
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Incisional hernia
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Deep vein thrombosis (DVT)/Pulmonary embolism (PE)
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Bleeding/haematoma/blood transfusion
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Chest infection
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New sexual problems e.g. dyspareunia
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Other infections (sepsis, septicaemia, abscess, respiratory)
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Inflammation, e.g. osteitis pubis
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Death
Reporting procedures
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Non-fatal expected SAEs and unexpected SAEs which are not causally related to the research procedures will not be reported to the Sponsor.
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Fatal expected SAEs and unexpected SAEs which are causally related to the research procedures (serious adverse reactions, SARs) will be reported to the study Sponsor within 24 h of staff becoming aware of the event. SARs will also be reported to the REC immediately.