Medial malleolus: Operative Or Non-operative (MOON) trial protocol - a prospective randomised controlled trial of operative versus non-operative management of associated medial malleolus fractures in unstable fractures of the ankle

Inclusion criteria are: 1) age ≥ 16 years; 2) able to consent to treatment; 3) unstable fracture dislocation of the ankle joint requiring operative intervention; 4) closed injury; 5) Weber B and Weber C fractures; and 6) surgery date within 2 weeks of date of fracture.

Exclusion criteria are: 1) patients unable to comply with post-operative data gathering including completing questionnaires in the English language; 2) additional lower limb injury which may impact on patient rehabilitation; 3) open fracture; 4) confirmed severe associated neurovascular injuries; 5) distal tibial intra-articular fractures/pilon-type injuries; 6) supination-adduction type 2 (SAD-2) fracture configurations with a medial malleolus vertical shear fracture; 7) patients medically unfit for surgery; 8) patients declining operative management; 9) non-residents, unable to return to the unit for follow-up for a period of 1 year; 10) current engagement in a pharmaceutical/drug trial; and 11) where the treating surgeon does not feel that inclusion in the trial is in the patients’ best interest either due to the fracture pattern or patient factors.

The primary outcome measure will be the OMAS. In total, 154 patients (77 per arm) will be required with 80% power and 5% (two-sided) significance to detect a clinically meaningful difference of 10 points on the OMAS scale at 12 months between the two groups [24‐26]. This assumes a standard deviation of 20 [27]. The sample size has been increased by 20% to account for any loss to follow-up.

Randomisation of treatment will be on a 1:1 ratio. Randomisation will be stratified according to age with a ‘young group’ (< 65 years) and an ‘older group’ (≥ 65 years). Based on retrospective data reporting the epidemiology of ankle fractures at our centre we will stratify on a 3:1 ratio between the ‘young’ and ‘old’. This will be factored into the computer-generated randomisation schedule, which will utilise a block design of mixed block sizes and will be generated by an independent statistician employed through the local university research methodology department. A member of staff independent of the trial will use this list to create 154 opaque sequentially sealed envelopes clearly distinguishing those for the young and old groups separately. Contained within each envelope will be a sticker bearing the words ‘Fixation’ or ‘Non-fixation’, which will be placed onto the study consent form.

Participants will be identified by members of the on-call admitting team as they attend the local hospital emergency department (ED) or who are referred to the outpatient trauma clinic. The trial will be introduced by a member of staff and a patient information sheet (PIS) specific to the trial will be given to the patient to consider. Once the patient has had time to read and consider the information, they will be approached by a member of the research team (one of four) who will clarify any points of uncertainty. The patient will be asked to sign a consent form providing their permission to enter the study and the next available randomisation envelope (age-dependent) will accompany the consent form into the operating theatre with the patient. The participant will not be aware of the result of randomisation at the point of study enrolment. The envelope will remain unopened until the operating surgeon has confirmed that the reduction of the medial malleolus fracture on an anteroposterior view is acceptable following fibular stabilisation. The envelope will be opened by a member of theatre staff who is independent of the trial. In the event that the fracture is not well-reduced, the envelope is returned in sequence back to the study office and the patient is withdrawn from the study. In the case of a trimalleolar fracture with an associated posterior malleolar fracture, fracture fixation will be at the discretion of the operating surgeon and influenced by the size of the fragment, articular congruity and presence of posterior talar subluxation. Examples of an acceptable and unacceptable intra-operative medial malleolar reduction are shown in Figs. 2 and 3.

Given the invasive nature of surgery those patients randomised to ‘Fixation’ will have an additional surgical wound on the medial aspect of their ankle and those who are randomised to ‘Non-fixation’ will not. It is therefore not possible to blind either the surgical team or the patients in this trial.

All participants, regardless of randomisation, will be reviewed back in the research outpatient clinic at 2 weeks, 6 weeks and at 1 year post-intervention. During the 2-week post-operative assessment, the wounds will be inspected, sutures removed by a dressings nurse and the patient will undergo anteroposterior (AP) and lateral radiographs of the ankle joint to ensure satisfactory talar reduction and no displacement of the metalwork or fractures. Immediate complications including infection, wound dehiscence and venous thromboembolic (VTE) disease will be documented. The 6-week, 8-week and 1-year assessment points will include further weightbearing AP and lateral radiographs to assess fracture union, talar reduction and radiographic evidence of osteoarthritis. Patients will complete the patient-reported outcome measures of OMAS, Manchester-Oxford Foot Questionnaire (MOXFQ), EuroQol 5D (EQ-5D), pain and treatment satisfaction on visual analogue scales (VAS), and return to work and sport. Complications will be documented. Physiotherapy will be organised at the discretion of the clinician reviewing the patient in the clinic to begin following the 6-week assessment. Postal questionnaires will be sent out at 3 and 6 months after surgery collecting the same outcome scores. The schedule of enrolment, interventions, and assessments as per the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) is summarised in Fig. 4.

The primary outcome measure will be the OMAS at 1 year following surgery [28]. This is a validated lower limb outcome score that has been used in large Health Technology Assessment (HTA)-funded trials concerning the ankle [24, 27]. This scoring system assesses patient-reported outcome across nine parameters: pain, stiffness, swelling, stair climbing, running, jumping, squatting, supports, and work/activities of daily living. A final score is calculated from 0 to 100, with 100 representing a better functional outcome. A recent study found that the OMAS had acceptable levels of internal consistency and test-retest validity, and correlated strongly with other lower limb injury outcome scoring systems and measures of general health, including the EQ-5D [29]. The primary null hypothesis is that there is no difference in outcome (primary outcome measure, OMAS) after 1 year between fixation of associated medial malleolus fractures and non-fixation in patients undergoing surgery for an unstable fracture of the ankle.

Secondary outcome measures include: 1) MOXFQ (Isis Innovation Ltd., Oxford, UK) [30], a validated and reliable patient-reported outcome measure for surgery of the foot and ankle, consisting of 16 items from three domains: walking/standing (seven items), pain (five items) and social interaction (four items) where each item is scored on a five-point Likert scale ranging from no limitation to maximum limitation (0, 1, 2, 3, 4); a raw score out of 64 is then converted to a 0–100 metric score, with 100 representing a better functional outcome; 2) EQ-5D [31], a standardised instrument for use as a measure of health outcome; 3) pain assessment measured on a VAS from 0 to 100 with 100 indicating no pain; 4) treatment satisfaction measured on a VAS from 0 to 100 with 100 indicating extremely satisfied; 5) time taken to return to work and sport (if applicable); 6) operative tourniquet time; and 7) complications including superficial and deep infection, nerve injury, chronic pain, failure of fixation, non-union, metalwork complications and re-operation.

The analysis of primary outcome data will include participants who have completed their 12-month follow-up, and will be analysed on an intention-to-treat basis. Statistical analysis will be performed by a senior statistician who is independent of the study and employed through the local university research methodology department. The primary outcome measure (OMAS at 1 year) will be compared between the two treatment groups using a two-way sample t test or non-parametric equivalent, dictated by the normality of the data. An analysis of covariance adjusting for age and the baseline patient-reported outcome measure (OMAS) will be performed. This method will also be used to compare other continuous outcome measure scores. The OMAS will also be collected at multiple time points to calculate change in outcome over time. This will be determined by fitting a linear regression to the 6-week to 12-month values of each participant and comparing the slope of the regression line between treatment arms. Comparison of binary outcomes such as the presence of non-union, infection and re-operation will be compared between the two treatment groups using a binominal test for comparison of proportions. Two-tailed p values will be presented wherever possible and a p value < 0.05 will be used to indicate statistical significance.

The study sample size has been increased by 20% to account for loss to follow-up at the primary outcome point (12 months). The primary outcome point will be collected at the final outpatient clinic appointment and, as such, it is anticipated that missing data for the primary outcome will be low. The participant dropout rate for each arm of the trial will be reported and compared. If the participant dropout rate at the primary outcome point is high, a sensitivity analysis may be performed. Missing data at the intermediate data collection points are most likely to occur at the 3- and 6-month assessment points as data collection is via postal questionnaire. However, by performing an analysis on change over time through fitting regression models the impact of missing data will be minimised.

Secondary outcome measures include complications, which will be closely monitored in both arms of the trial. This trial will be conducted in line with the Academic and Clinical Central Office for Research and Development (ACCORD) published guidelines: Identifying, Recording and Reporting Adverse Events for Clinical Investigations of Medical Devices.

The first patient was recruited on 24 October 2017. The expected date of completion is February 2021.