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

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 a secure, web-based service to ensure allocation concealment. PROJECT PLAN: The study will take 72 months* recruiting (@2 cases/month/site) over 47 months* at around 30 sites. Follow-up will be at 3 months, 6 months, 1 and 2 years. (* Extended from 66 months (study duration) and 30 months (recruitment) to account for delays incurred due to pause to recruitment due to COVID-19). 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 3 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 and estimate the agreement between these methods in measuring extension deficit/recurrence. Clear instructions (7) will be given to standardise the photo-taking