This pRCT will be conducted at three academic trauma units at three different urban centres in Ireland. Each centre serves a referral population of > 500,000 and receives all grades of trauma from both urban and rural environments on a 24-hour basis. A trauma team is on call daily and includes two trainee surgeons and a consultant orthopaedic surgeon. Surgeries are performed by in part, in total or supervised by consultant orthopaedic surgeons. Regional and general anaesthesia is used at the discretion of the anaesthetist. Ankle fracture surgery is conducted on both a day case or overnight basis. Ward based physiotherapy is provided daily to facilitate early discharges. All hospital personnel contributing towards recruitment and patient pathway in this trial will undergo training in the objectives and methodology of the study.
Patient recruitment and consent:
All patients admitted to the hospital with ankle fracture (AO/OTA 44A1.3 to 44A3.3, 44B and 44C ) deemed appropriate for surgical intervention will be asked to participate in the trial and provided with a patient information leaflet (Appendix 1), given time to read the document and ask questions. If the patient agrees to enter the trial, they will sign the consent form in the presence of the admitting doctor on the morning of or the night before their surgery.
Randomisation will occur upon skin closure. The circulating theatre nurse will consult the randomised block database and inform the surgical team that a walking boot (Group A) or a cast (Group B) is to be applied. The patient’s details will be entered into the database and they will be assigned a trial number.
In accordance with a pragmatic study, surgical approach and choice of implant will be at the surgeon’s discretion. Surgeons may or may not be authors in the study. Surgical practice at the three institutions is to achieve anatomical reduction and rigid fixation. The commonly used osteosynthesis systems for fixation is the Small Fragment System, with One-Third Tubular plate commonly used. The use of locking mode is not routinely used. Other systems are also available. All patients will be assessed by a physiotherapist for gait stability and provided with walking aids according to randomisation. Patients in the walking boot group (Group A) will be instructed to weight-bear as tolerated immediately with or without walking aids for balance. Patients in the NWB group (Group B) will be instructed to strictly non-weight bear using crutches or frame for a total of six weeks. Group A will be instructed to remove the walking boot four times a day at minimum to perform ankle range of motion exercises until they attend outpatient physiotherapy following their first post-operative visit. All patients will receive a post-operative care information sheet according to their grouping (Appendix 2 and 3).
Patients will be followed up in an outpatient setting at two weeks, six weeks, twelve weeks, six months and one year postoperatively. At each visit, the OMAS and SF-36 Health questionnaire will be collected by one of two study investigators. Surgeons that may or may not be authors in the study reviewing patients in either group will also record surgical site assessment, x-ray evaluation, ankle ROM (using goniometry), information regarding return to work, confirmation of physiotherapy referral and confirmation of collection of OMAS and SF-36 questionnaire according to a Case Report Form (Appendix 4).
All skeletally mature, acute ankle fractures treated with anatomical reduction and stable internal fixation including; (AO/OTA 44A1.3 to 44A3.3, 44B and 44C)
- Isolated lateral malleolus fractures
- Isolated medial malleolus fractures
- Bi-malleolar fractures
- Tri-malleolar fractures
- Syndesmosis injuries that have been surgically fixed with either screw or tightrope.
- Closed, grade I, or grade II open fractures.
- Skeletal immaturity
- Gustilo grade-III open fractures
- Tibial plafond fractures
- Polytraumatised patients
- Non-ambulatory status before injury
- Expected insufficient stable fracture fixation with standard surgical technique
- Pre-existent cognitive disability, neurological disease or inability to comply with non-weight-bearing mobilisation and inability to comply with follow-up.
- Grossly comminuted fragility fractures
Who Will Take Informed Consent?
The admitting trainee or consultant surgeon will obtain consent after providing appropriate information and patient information leaflet (Appendix 1).
Additional consent provisions for collection and use of participant data and biological specimens
Not applicable as no biological specimens were collected as part of this trial.
Explanation for the choice of comparators
The traditional non-weight bearing (NWB) cast immobilisation is a common practice in many centres, and this protocol could be not necessary.
Patients will be allocated randomly to one of two groups;
- Will receive a walking boot orthosis postoperatively in theatre and allowed weight bearing as tolerated and range of motion (ROM) exercises immediately.
- Will be encouraged to elevate the affected foot in the first two weeks to reduce swelling.
- The first follow up appointment will be after two weeks. This visit is for surgical site inspection, removal of sutures, check x-ray and referred to physiotherapy to continue ROM exercises and weight-bearing as tolerated progressing to full weight-bearing.
- Will receive full below-knee cast postoperatively in theatre and prevented from weight-bearing with for six weeks.
- Will be encouraged to elevate the foot in the first two weeks to reduce swelling.
- The first follow up appointment is after two weeks. This visit is for surgical site inspection, removal of sutures, check x-ray and re-application of a full below-knee cast.
- The second follow up is after six weeks, for removal of cast and referral to physiotherapy to commence ankle ROM exercises and weight-bearing as tolerated progressing to full weight-bearing.
Criteria For Discontinuing Or Modifying Allocated Interventions
The trial will be terminated early if 20% complication rate detected in either of the treatment groups (10,13).
Strategies To Improve Adherence To Interventions
As the intervention is visible and the trail could not be blinded, the operating surgeon will not be informed with the randomisation sequence until after the end of surgical fixation.
A regular internal audit process is established to ensure adherent to the ankle trial protocol and increase compliance with recruitment process; this will provide detailed information about all patients with an ankle fracture that is admitted to hospital (included or excluded from the trail).
In the post-operative setting on the ward and before discharge, a physiotherapist will reinforce the patient’s role in the trial and provide them with information leaflet appropriate to their grouping. At subsequent outpatient follow up attendances, patients will be reminded of the trial. The trial Case Report Form (Appendix 4) will record if the patients have received outpatient physiotherapy.
Relevant concomitant care permitted or prohibited during the trial
The choice of and duration of DVT prophylaxis will be at the surgeon’s discretion.
Provisions For Post-trial Care
The primary outcome measure is the functional Olerud-Molander Ankle Score (OMAS). This score ranges from 0 to 100, with 100 representing the normal ankle function (14). Secondary outcome measures include; complication rate (infection and fixation failure), total arc of ankle motion (plantar flexion and dorsal-flection) measured in degrees using a goniometer, RAND 36-Item Short Form Survey (SF-36) scoring, the time needed to return to work in days and postoperative hospitalisation length in days.
Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) Figure of enrolment, interventions and assessments.
Key: IWBAT immediate weight-bearing as tolerated, NWB non-weight-bearing, OMAS Olerud Molander Ankle Score, RAND SF-36 36-items Short Form Health Survey.
An a priori power analysis for the superiority of treatment with immediate weight-bearing and ROM will be conducted for this hypothesis. To detect a clinically significant 10 points difference on the Olerud and Molander Ankle Score (OMAS) at six weeks with a standard deviation of 19(15–18). Alpha = 0.05 and β = 0.20 (80% power), two-sided test and a maximum loss of follow up of 20%, a sample size of 70 per each group is necessary.
Please see the recruitment above. As this is a multi-centre pragmatic trial examining a common fracture, the target number is achievable.
Assignment Of Interventions:
An online computer-generated block randomisation list (20 patients per block) will be created at the start of the trial via the website http://www.randomization.com.
Circulating theatre nurse will check the randomisation sequence by accessing the trial excel sheet and inform the surgeon upon skin closure surgery and enter the patient’s details in randomisation slot.
Who will generate the allocation sequence: The Principal investigator.
Who will enrol participants: admitting trainee surgeon.
Who will assign participants to interventions: Circulating theatre nurse.
Assignment of interventions:
Who will be blinded
It is not possible to blind the intervention from the participant nor the surgeons as it is external and visible (cast or boot). However, to reduce the risk of bias, the surgeon will be blinded with the sequence of randomisation until the surgery is completed.
Procedure For Unblinding If Needed
It is not possible to blind the intervention.
Data collection and management
Plans For Assessment And Collection Of Outcomes
At each follow-up visit, the OMAS and SF-36 Health questionnaire will be collected from the participants by outpatient clinic nurse. The attending orthopaedic consultant or NCHD fills up a case report form, and this includes documentation of the following information; surgical site assessment, x-ray evaluation, ankle total arc measure (goniometry), information regarding return to work, confirmation of physiotherapy referral and confirmation of collection of OMAS and RAND SF-36 Health survey.
Plans To Promote Participant Retention And Complete Follow-up
We have developed a patients tracking system to allow the researchers to monitor follow up carefully. As part of this system, a weekly list of expected patients is provided to the research nurse in the OPD, and this list is reviewed on a daily bases to record attendance. In case of a patient being absent from the clinic, another appointment for the following week will be arranged, the RAND SF-36 and the OMAS score will be posted to the patients with pre-paid envelope enclosed and the patient will be contacted to encourage follow up.
Three forms are collected at each follow-up visit and stored securely in the trial locker, two PROM forms, the RAND SF-36 and OMAS and the case report form. Periodically, all data is transferred to a temporal database located within the HSE computer system by two researchers, and a read-only copy is stored in a separate folder. This is then cross-checked before data is transferred to STATA16 and PRISM for statistical analysis and reporting by the research team and statistician.
RAND SF-36 is multiple steps analysis; this will be performed with oblique scoring rather than the orthogonal-factor analytic model (19). Normative data for the Irish population will be used as a reference (20).
Data management will be in accordance with the General Data Protection Regulation
(GDPR) Health Service Executive (HSE) and Health Research regulations (21,22). Data will be kept anonymously in the database within the HSE local hospital computer system in protected folders to ensure confidentiality. Paperwork will be stored in the trail locker in a locked researcher office within the hospitals.
Plans for collection, laboratory evaluation and storage of biological specimens for genetic or molecular analysis in this trial/future use
Statistical methods for primary and secondary outcomes
Unpaired t-test will be used for continuous data such as, OMAS, SF-36, total ankle arc, return to work (days), length of hospital stay (days). For categorical data such as rate of infection and other demographic data, Chi-squared test or Fisher’s exact test will be used as indicated. Adjustment for strong predictors of the outcome, such as fracture complexity determined by fracture classification will be performed if necessary. Continuous data will be summarised as mean and standard deviation and confidence intervals (CI) (95% CI and p-value threshold ≤ 0.05) A p-value of < 0.05 will be considered significant. Categorical data will be presented as frequencies and proportions. STATA16 and PRISM software will be used for statistical analysis. Analysis will be conducted on the intention-to-treat (ITT) basis.
No planned interim analysis.
Methods For Additional Analyses (e.g. Subgroup Analyses)
Additional subgroup analysis comparing the outcomes of different fracture complexity pattern will be performed.
Methods in analysis to handle protocol non-adherence and any statistical methods to handle missing data
Any protocol non-adherence will be disclosed and handled accordingly. Effort will be made to prevent missing of data as much as possible, and unavoidable missing data, such as withdrawals from the study or loss of follow up data will be analysed on an intention to treat basis including sensitivity analysis. Methods such as Observation carried forward (LOCF), or imputation will only be used when scientifically justified (23–25).
Plans to give access to the full protocol, participant level-data and statistical code
The full protocol is available at the registry website and will be published in one of the trial protocols journals.
Oversight And Monitoring
Composition of the coordinating centre and trial steering committee
Four authors at the coordinating centre (University Hospital Waterford) take responsibility for the scientific validity of the study protocol, assessment of study quality and conduct, as well as, for the scientific quality of the final study report.
Composition of the data monitoring committee, its role and reporting structure
The authors understand the composition for a data monitoring committee for this trial is not necessary and will not add much to the study. This non-funded trail does not involve the administration of medication and does not expose patients to significant harm; the composition of DMC may even be counterproductive (26).
Adverse Event Reporting And Harms
Collected case report forms are checked daily by the research team before stored in the trial locker; any adverse event or harm will be communicated with the study team.
Frequency And Plans For Auditing Trial Conduct
The trial conduct is continuously audited in the departmental audit meeting (three monthly).
Plans for communicating important protocol amendments to relevant parties (e.g. trial participants, ethical committees)
Any change to the trial protocol will be communicated with the ethical committees and trial registry.
The result of this trial will be published in one of the medical journals.