Title: DISC: Dupuytren’s Interventions Surgery vs. Collagenase. A pragmatic multi-centre randomised controlled non-inferiority, cost effectiveness trial comparing injections of collagenase into the cord to surgical correction in the treatment of moderate Dupuytren’s contracture in adult patients
Funder: Department of Health and Social Care

Abstract: DESIGN: Multi-centre, open-label, two-arm parallel group, pragmatic, randomised controlled trial to establish if injecting collagenase with manipulation is clinically not inferior and is cost-effective compared to limited fasciectomy for moderate Dupuytren’s contracture (DC). We will undertake an economic evaluation alongside the RCT. Also, a nested qualitative study will explore the advantages and drawbacks of treatment from the patient’s viewpoint. Consenting adults with a discrete palpable cord causing moderate metacarpophalangeal (MCP) or proximal interphalangeal (PIP) joint contracture that have not had previous surgery to the same hand will be included. The primary outcome is the validated Patient Evaluation Measure (1) (PEM). The primary time point is 1 year, to allow assessment of impact of deformity correction on function. Secondary outcomes include the URAM (2), the Michigan Hand Questionnaire (MHQ)(3), recurrence (measured by extension deficit) and EQ-5D-5L. Data on aftercare (e.g. physiotherapy or splintage), further procedures and adverse events will be collected. The trial is pragmatic. Surgeons will follow local guidelines, and we will not standardise post-treatment care. The study is a Clinical Trial of Investigational Medicinal Product (Clinical Trials Regulations 2004). SAMPLE SIZE: To establish non-inferiority within a margin of 6 PEM points for the lower limit of a two-sided 95% CI with 90% power, we will recruit 710 participants, allowing for 20% attrition at 1 year. It also gives at least 80% power to detect a difference in recurrence rates of 10% or more (based on 12% in the surgery arm (4) and 35% or more in the collagenase arm (5)) at 2 years assuming a further 10% dropout. RANDOMISATION: Randomisation will be done by York Trials Unit's secure, web-based service to ensure allocation concealment. PROJECT PLAN: The study will take 66 months, recruiting (@2 cases/month/site) over 30 months at around 18 sites. Follow-up will be at 3 months, 6 months, 1 and 2 years. A 6 month pilot (Phase 1) at the start of recruitment will aim to recruit 48 patients from 6 pilot sites to confirm screening and recruitment assumptions, followed by full recruitment and follow-up (Phase 2). STATISTICAL ANALYSIS: Group differences in PEM scores at 1 year will be analysed using repeated measures regression methods, adjusting for contracted joints (MCP or PIP) and other baseline covariates. Continuous secondary outcomes (e.g. URAM, MHQ) will be analysed using similar models. Recurrence, complications and other binary secondary outcomes will be analysed by logistic regression. HEALTH ECONOMICS: We will compare the incremental cost per QALY (6), using utility data from the EQ-5D-5L. Costs and outcomes will be presented for the study period and extrapolated to a longer time horizon if appropriate. The potential value of further research will be assessed. QUALITATIVE ASSESSMENT: We will interview (at around 6 months) about 40 participants to identify the benefits and difficulties that patients perceive for each treatment. Data will be analysed thematically to inform an iterative and developing series of topics. SUB-STUDY: We will collect participant-taken photographs in addition to goniometric measurements at 1 year follow-up and estimate the agreement between these methods in measuring extension deficit/recurrence. Clear instructions (7) will be given to standardise the photo-taking

Lay abstract: Dupuytren’s contracture is the fourth most common problem affecting the hand in the UK. The disorder occurs in adults, mainly affecting men, and is caused by fibrous tissue, which forces the finger to bend down into the palm. Although it is rarely painful, patients cannot straighten the finger and this increasingly interferes with hand function. In England around 17,000 patients have surgery to straighten the bent finger by removing the fibrous tissue causing Dupuytren’s contracture each year, at a cost of over £60 million. This is the common and accepted treatment. An alternative to surgery is a newly introduced collagenase injection, which softens the fibrous tissue that causes the condition, given in the clinic. The patient is followed up a few days later in clinic and the finger is manipulated, in an attempt to straighten it. Both these treatments are offered on the NHS in England and are used in the USA and Europe. It is currently not known if the injection is as good as surgery at correcting finger deformity and if the correction is maintained in the long term. We also do not know whether the complication rates are similar. Early findings suggest that patients who have collagenase treatment might be more likely to have the condition return in the longer term. However, if proven effective, the injection does have the advantage of avoiding surgery, and provides an alternative for those who cannot have surgery. The DISC study will investigate if an injection of collagenase is as good as surgery at treating this condition, and whether the effects of treatment are sustained in the short term. The best way to investigate these questions is by doing a randomised study. This means that, as part of the study, the patient and surgeon agree to use whatever treatment (surgery or collagenase injection) is allocated to them by chance (randomly). This is the best way to make sure that two comparable groups are created at the start, thereby allowing reasonably objective conclusions to be made from the study. After treatment, patients will be seen at regular intervals. Our patient advisors have confirmed that these intervals are appropriate for their condition. Questionnaires will be used to assess how patients taking part in the study feel about their hand over a 2 year period, and the bend in the finger will be measured at intervals after treatment. Our patients have advised us that these forms are clear and easy to complete, and that if they were taking part they would be happy to fill these in at regular intervals. They also confirmed that the forms we propose would adequately capture the impact of their condition and the impact of treatment including that of any complications. The study will also find out the cost of both treatments, both at 1 year and 2 years, to find out which is better value for money. It will look at the impact of these two treatments on hospital resources, including beds and operating theatre time. We will also talk to our patients to discover what they think about the different treatments, to see if they have any preference for treatment, and to see if they can help us to develop more effective services for the future.

Research activity codes: 6.4 SURGERY
Health categories: MUSCULOSKELETAL