Title: Clarifying the management of men with recurrent urethral stricture disease: A randomised trial of open urethroplasty versus endoscopic urethrotomy (OPEN)
Funder: Department of Health and Social Care

Abstract: DESIGN: A multi-centre pragmatic randomised superiority trial comparing open urethroplasty (experimental) against endoscopic urethrotomy (control) for men with recurrent bulbar urethral stricture. Within-trial and long-term cost-utility analyses will be performed. An initial feasibility phase will assess ability to recruit to target. SETTING: Thirty-five secondary care NHS Trusts undertaking urethral surgery. TARGET POPULATION: Adult men needing treatment for first recurrence of bulbar urethral stricture. HEALTH TECHNOLOGIES: The control intervention is endoscopic urethrotomy which uses a blade mounted on an endoscope to cut the stricture internally under vision. The alternative is open urethroplasty where the urethra is surgically reconstructed through a skin incision beneath the scrotum. MEASUREMENT OF COSTS AND OUTCOMES: Outcome data will be recorded by participants under a unique identifier on questionnaires which will be made available in paper and electronic formats, and on the case report form by trial co-ordinators at each centre. Data will subsequently be entered electronically onto a clinical data management system for central storage. Symptom control over the 24 months trial period will be measured through the ICIQ-MaleSF symptom score at baseline prior to randomisation, just prior to surgery, one week after catheter removal, and at 3, 6, 12, 18, and 24 months after intervention together with additional flexible time points when re-intervention for disease recurrence occurs. The associated condition-specific quality of life measure (ICIQ-MaleSF QoL), a single item sexual dysfunction scale (IEEF) and a generic QoL measure (EQ-5D) will be completed at the same points; quality adjusted life years (QALYs) will be calculated. Urinary flow rate measurements at baseline, 6 and 24 months will be entered on the case report form. Stricture recurrence and further intervention for stricture will be recorded by patient questionnaire at 6, 12 and 24 months, and from the clinical record at 24 months. Recurrence and need for further intervention will be validated by an expert panel. Adverse effects will be identified from the clinical record and by participant questionnaire at 6, 12 and 24 months. Use of secondary care services will be captured on the case report form post-operatively and at 6, 12 and 24 months. These will be costed using site specific estimates or central NHS sources. Events incurring primary care or societal costs will be recorded by participant questionnaire at 6, 12 and 24 months, with costs calculated from standard sources. A model will be used to extrapolate the findings of the cost-utility analysis over a 10-year time horizon. During the early feasibility phase semi-structured interviews with men eligible for the trial and their clinicians will be thematically analysed to assess decisional conflict between the two procedures. The time trade off method will be used to explore valuation of short term health states not captured by standard quality of life instruments. Sensitivity analysis will be used to explore imprecision and uncertainty surrounding the estimates used for the cost-utility analyses. SAMPLE SIZE: We aim to detect a 0.3 of a standard deviation (SD) difference in the area under the curve for repeated measurement of the ICIQ-MaleSF symptom score over 24 months (primary outcome). To achieve this with 90% power (2-sided 5% significance level), 235 participants per group (470 in total) are required. To allow for the anticipated 5% of participants where the primary outcome cannot be calculated because of completely missing data, we plan to randomise 500 participants. Based on similar trials we estimate a 55% agreement to participate rate requiring 910 men to be approached. The feasibility phase requires completion of at least 45 site-months of recruitment with randomisation of 31 participants. In the first six months we aim to interview up to 20 men eligible for the trial (including some not consenting to randomisation) and up to 12 clinicians.

Lay abstract: BACKGROUND: About 60,000 younger men aged less than 65 years in the UK suffer from urethral stricture, a narrowing of the urinary channel just beyond the bladder (bulbar urethra). The stricture causes trouble passing urine which is embarrassing for men and often leads to urine infection requiring time off work and visits to their GP. The standard initial treatment is stretching of the urethra with a telescope – endoscopic urethrotomy, and about 15,000 of these procedures are carried out in the NHS each year at a cost of over £10 million. This doesn’t usually cure the problem and men have to come back for repeated urethrotomies, typically every two years, resulting in a continued burden for patients, ongoing costs for the NHS, and damage to healthy parts of the urethra. Recently a new operation called open urethroplasty has been developed whereby the urethra is surgically reconstructed through an incision in the skin beneath the scrotum. Open urethroplasty seems to have a much higher chance of curing the problem, preventing further symptoms and the need for regular stretches. It does however require more surgical expertise, and men have to have a urinary catheter in place for 2 weeks rather than the 2 days with urethrotomy. At present we don’t know for sure which procedure is best suited to stopping recurrence of the stricture and improving men’s symptoms, and which provides best value for money to the NHS. Because of this uncertainty doctors find it difficult to recommend one treatment or another and the men themselves are unable to make an informed choice between the treatments. To resolve this dilemma we intend to carry out a randomised clinical trial in a group of men with recurrent urethral strictures to find out which procedure is most effective, and use the results to predict the health benefits for these men and the financial implications for the NHS, over 10 years. AIMS: Our research questions are: Do open urethroplasty and endoscopic urethrotomy for urethral strictures differ regarding effective symptomatic relief of the condition? And; Does open urethroplasty provide better value in terms of cost and health benefit than endoscopic urethrotomy for both patients and the NHS? THE PROJECT: We plan a randomised controlled trial carried out in 35 NHS hospitals. We will ask men who need treatment for the first recurrence of a bulbar urethral stricture, and who are undecided as to which option is best whether they would be happy for a computer to randomly decide which treatment they will have. We need to randomise at least 250 men to undergo each of the two options of endoscopic urethrotomy and open urethroplasty. The care received will follow routine clinical practice in each hospital. We will monitor all the participants for the 2 years following their treatment, focusing on change in urinary symptoms, general well-being, measurements of urinary flow rate and whether men suffer further recurrence of the stricture. We will also record any problems they encounter linked to the operation such as infections and needing time off work, and collect information on the costs of each treatment. Since it is sometimes difficult to explain to patients the value of participating in this kind of research we will use the first 6 months of the project to refine the information we give about the trial and to make sure over the first 10 months that we are likely to be able to recruit sufficient participants to answer the research questions. OUTCOMES: We have designed the study to show whether or not men having urethroplasty have less urinary symptoms over the 2 years following initial treatment compared with men having a urethotomy. If this is the case we can confidently say that urethroplasty is the better treatment. We will also compare the stricture recurrence rate and the need for further interventions following urethroplasty and urethrotomy . We will decide which intervention provides the best value for money by calculating how much needs to be spent to achieve improvement in general well-being that is recorded for the most effective treatment. We will also follow the men who particpate over the subsequent ten years through their NHS records to make sure that our predictions are correct. END OF TRIAL: Once we have looked at all the outcomes for men in the trial and decided what the results mean we will make sure that everybody who has an interest in urethral stricture disease knows what the trial has shown. This will include articles in medical and general magazines, reports to our funder, publicity reports to other media such as television, and inclusion in treatment guidelines and patient information material.

Research activity codes: 6.4 SURGERY;7.3 MANAGEMENT AND DECISION MAKING
Health categories: RENAL AND UROGENITAL