Title: Hand-2: Needle fasciotomy versus limited fasciectomy for treatment of Dupuytren’s contractures of fingers: a randomised non-inferiority trial with an individual participant data network meta-analysis comparison with DISC (ISRCTN18254597) to compare outcomes after collagenase injections
Funder: Department of Health and Social Care

Abstract: BACKGROUND_x000D_ Dupuytren’s contractures (DC) are scar-like tissue that form under the skin of the palm of the hand, causing one or more fingers to bend into the palm (www.nhs.uk/conditions/dupuytrens-contracture/). They prevent them from straightening fully which causes difficulty with many everyday tasks like washing, dressing, or using a computer keyboard. It is common: in 2016 NHS England spent £36M treating 16,700 patients with DC._x000D_ _x000D_ AIM_x000D_ DC are most commonly treated using one of two procedures and we don’t know which is best. _x000D_ 1. Needle fasciotomy (NF) involves cutting the contracture by moving a medical needle back and forth through it until it snaps, releasing the finger. It can be done in a clinic room and leaves no skin wound. Recovery takes 1-2 weeks_x000D_ 2. Limited fasciectomy (LF) involves cutting out the contractures and stitching the skin up. This is done in an operating theatre with the patient asleep or the arm “frozen”. Recovery takes 4-12 weeks. About 8 in 10 treatments done currently are LF._x000D_ _x000D_ The problem can come back (recur) after either treatment. Studies suggest that this happens sooner and more commonly with NF, but LF has a greater risk of causing other problems which restrict hand function, like finger stiffness and pain. NF is cheaper for the NHS, but any savings may be offset by an increased need for future treatments after recurrence._x000D_ _x000D_ The aim of the study is to determine: a) whether NF is not substantially worse than LF at preserving hand function and; b) which treatment offers best value for money. _x000D_ _x000D_ DESIGN AND METHODS_x000D_ We recently completed an NIHR funded “feasibility study” of NF versus LF (HAND-1) to see whether a large study like this is possible. The feasibility work showed a large study is possible and acceptable to staff and patients. We used it to inform the design of this study._x000D_ _x000D_ We will recruit adults with DC in one or more untreated fingers. They will be randomly allocated by a computer to have treatment with either NF or LF. We will follow everyone up at 3 and 6 weeks, and 6, 12 and 24 months. The main outcome is the Patient Evaluation Measure, a patient-reported measure about hand function, at 12 months after surgery. We will also compare other measures of hand function, overall health, finger straightness, recurrence and costs._x000D_ _x000D_ We will recruit 406 people from 12 hospitals over 21 months. We will ask for permission to contact them 3-5 years after treatment to gain more information about their hands in the longer term._x000D_ _x000D_ We have arranged to share our results with a research team comparing limited fasciectomy with a third treatment option, collagenase injections, in another study funded by NIHR. This will provide even more information on how best to treat DC._x000D_ _x000D_ PATIENT AND PUBLIC INVOLVEMENT_x000D_ This study addresses an important question from a James Lind Alliance Priority Setting Partnership which brought together patients and clinicians to identify the top research questions in hand surgery._x000D_ _x000D_ People with DC in HAND-1 helped us choose the primary outcome measure for this study and:_x000D_ a) were positive about their involvement and provided feedback _x000D_ b) found both treatments acceptable_x000D_ c) were satisfied with the function and appearance of the hand after treatment._x000D_ _x000D_ The research team is experienced and includes hand surgeons, patients, statisticians, qualitative researchers and people with expertise in delivering large studies in surgery across the UK.

Lay abstract: RESEARCH QUESTION_x000D_ What are the clinical and cost effectiveness of:_x000D_ _x000D_ a. needle fasciotomy (NF) compared to limited fasciectomy (LF) - Main Study_x000D_ b. NF compared to collagenase injections (CI) - Network Meta-Analysis _x000D_ _x000D_ in the treatment of Dupuytren’s contractures (DC)?_x000D_ _x000D_ BACKGROUND_x000D_ DC are common and impair hand function. Currently there is no high quality evidence to guide treatment. NF and LF are both used as standard care in the NHS, with choice of treatment often based on the surgeon’s preferences. Recently CI has been introduced as a treatment option and may have benefit over NF or LF._x000D_ _x000D_ MAIN STUDY_x000D_ _x000D_ PRIMARY OBJECTIVE_x000D_ Is needle fasciotomy non-inferior to limited fasciectomy in terms of hand function 12 months post-treatment?_x000D_ _x000D_ SECONDARY OBJECTIVES_x000D_ To compare NF and LF for short-term recovery and at 24 months for:_x000D_ a. complication and re-operation rates_x000D_ b. health-related Quality of Life, healthcare resource use and cost effectiveness_x000D_ c. treatment acceptability (qualitative study)_x000D_ _x000D_ DESIGN (guided by Hand-1: Feasibility study): A pragmatic, multi-centre, two-arm, parallel, randomised non-inferiority trial comparing outcomes of needle fasciotomy and limited fasciectomy. There is an internal pilot phase which will review recruitment (10 months) and retention (18 months)._x000D_ _x000D_ SETTING: 12 UK NHS Trusts_x000D_ _x000D_ STUDY POPULATION: Adults referred to secondary care with Dupuytren’s contractures in an untreated finger that satisfies the NHS/CCG criteria for intervention and is suitable for treatment with either NF or LF._x000D_ Adults with isolated DC of the distal interphalangeal joint, and those who are unable to adhere to trial procedures or complete questionnaires are excluded._x000D_ _x000D_ PRIMARY OUTCOME_x000D_ • Part 2 of Patient Evaluation Measure (PEM) at 12 months post-treatment_x000D_ _x000D_ SECONDARY OUTCOMES_x000D_ • PROMS: MyMOP(2), SANE, EQ-5D-5L_x000D_ • restricted finger extension_x000D_ • adverse effects_x000D_ • NHS resource use_x000D_ • lost productivity and return to usual activities_x000D_ _x000D_ SAMPLE SIZE: 406 participants (203 per arm), recruited over 21 months from 12 sites. _x000D_ _x000D_ NETWORK META-ANALYSIS (NMA) WITH INDIVIDUAL PARTICIPANT DATA_x000D_ Hand-2 is designed to allow comparison of its outcomes with those of LF and CI in an ongoing NIHR study (DISC, ISRCTN18254597)_x000D_ _x000D_ PRIMARY OBJECTIVE_x000D_ To compare hand function 12 months after treatment with NF (Hand-2) and CI (DISC)._x000D_ _x000D_ SECONDARY OBJECTIVES_x000D_ To compare NF and CI for short-term recovery and, at 24 months:_x000D_ • complication and re-operation rates_x000D_ • healthcare resource use, Health-related Quality of Life and cost effectiveness._x000D_ _x000D_ TIMELINE (months)_x000D_ 1-6 Trial set-up, finalise main study, meta-analysis protocols, approvals_x000D_ 7-12 Set-up 12 recruiting sites_x000D_ 8-16 Pilot recruitment_x000D_ 17 Review 1 - Review of recruitment_x000D_ 17-28 Full recruitment_x000D_ 25 Review 2 - Review of recruitment + retention_x000D_ 29-30 Complete final surgeries (average 2 month waiting time)_x000D_ 29-54 24 month Follow-up_x000D_ 54 Data cleaning and lock_x000D_ 55-60 Analysis, NMA + write-up_x000D_ _x000D_ IMPACT + DISSEMINATION_x000D_ The trial will determine whether NF produces non-inferior outcomes to LF and is cost-effective. The NMA will compare the outcomes and costs of CI, NF and LF. Both will inform the treatment of DC in the NHS._x000D_ Study findings will be disseminated by HTA monograph, publications and presentations, and sent to guideline developers and health purchasers. The British Dupuytren’s Society (patient group) and BSSH will host lay summaries of the trial findings on their websites and use their social media outlets to disseminate them.

Research activity codes: 6.4 SURGERY
Health categories: MUSCULOSKELETAL