Weight bearing or non-weight bearing after surgically fixed ankle fractures, the WOW! Study: study protocol for a randomized controlled trial

This is a prospective multicenter randomized controlled trial involving six hospitals in the Netherlands. The study has been approved by the local Institutional Review Board under protocol number WOW-01/NL40835.100.12. This study compares three different post-operative care regimens after ankle surgery; all patients with a Lauge Hansen supination exorotation type 2, 3 or 4 ankle fractures requiring surgical treatment are eligible for inclusion.

After registration of the patient, an anonymous X-ray is sent to an expert panel consisting of six experienced orthopedic trauma surgeons. The fracture is classified according to the Lauge Hansen classification and advice on whether or not operative fixation is indicated is provided within 24 hours. A patient is eligible for inclusion when a majority of the expert panel agrees that operative fixation is necessary and the fracture type meets the inclusion criteria. When votes are split equally, the chairman (LL) is the tiebreaker. A flow chart of the study is shown in Figure 1.

Non-pregnant, Dutch speaking patients are being recruited from the participating hospitals in the emergency room or pre-operatively during an outpatient department visit. Patients are screened for eligibility according to the inclusion and exclusion criteria (Table 1). The treating physician or study staff explains the study and informed consent is obtained from each patient. Retrospective data of the participating hospitals shows that approximately 395 patients per year undergo surgery for ankle fractures. Approximately 20% of these patients would be eligible for enrollment according to our inclusion criteria. If this trend continues, we anticipate enrollment of 79 patients per year (Table 1).

All patients between 18 and 65 years with a Lauge Hansen supination exorotation type 2, 3 and 4 ankle fractures are eligible for inclusion (Figure 2). Exclusion criteria include pre-existent impaired morbidity, cognitive disability, body mass index >30, and diabetes mellitus. All inclusion and exclusion criteria are listed in Table 1.

After enrollment, patients are scheduled for surgery. The ankle fixation technique is ultimately determined by the treating physician; however, advice is provided by the expert panel based on the X-ray. After surgery, all patients are randomized to one of three post-operative care regimens: 1) unprotected non-weight-bearing group – functional weight bearing as tolerated; 2) protected weight-bearing group – weight bearing as tolerated with a below knee cast for 6 weeks; 3) unprotected weight-bearing group – mobilization with crutches, active ankle exercises. All patients see a physiotherapist post-operatively or after cast removal to learn exercises and receive advice on how to start mobilizing according to their specific post-operative care regimen. The physiotherapists have been instructed by the investigators. Patients in the protected weight-bearing group receive low molecular weight heparin as thrombosis prophylaxis for the entire duration of immobilization. For the unprotected non-weight-bearing and unprotected weight-bearing groups, anti-thrombotic treatment is not indicated.

Patients are randomized using computerized block randomization to either protected weight bearing, unprotected non-weight bearing, or unprotected weight bearing. The randomization is stratified by the participating hospitals. The blocks for randomization consist of 21 patients with the three post-operative care regimens equally represented in each block. Follow-up is by the intention-to-treat principle. Following surgical fixation, the treating surgeon logs into the private website where the patient is randomized to one of three post-operative care regimens.

Patients are treated during same day admission if possible. According to their post-operative care regimen, patients receive a cast, exercise instructions, and a physiotherapist referral letter. All patients are reviewed in the outpatient clinic by the treating surgeon and/or investigator at 2 weeks, 6 weeks, 3 months, 6 months, and 1 year after surgery. At all post-operative outpatient visits, a standardized clinical exam is conducted including three standardized patient reported outcome questionnaires; the Olerud Molander Ankle Score (OMAS), the Short Form-36 (SF-36), and the Visual Analogue Scale (Table 2).

The OMAS is a scoring scale for symptom evaluation in patients with an ankle fracture and in patients with other acute ankle injuries [17]. This score ranges from 0 to 100%, with 100% representing normal ankle function [17]. It was developed specifically as a comparative research measure to improve consistency and uniformity in ankle injury reporting [17]. A difference of 5 to 10 points between two groups on the OMAS is defined as a clinically relevant result.

The SF-36 is one of the most widely used generic health questionnaires. It was developed as a medical outcome score to measure the functional health status of a patient [18,19]. It has been translated into Dutch and validated as a useful questionnaire to assess a broad array of health-related quality-of-life issues [19].

Other secondary measures of function include range of motion (ROM) (plantar and dorso-flexion), weight-bearing pressure load, and calf wasting (difference in calf circumference at enrollment and at 12 weeks post-operative) of the injured ankle. Pain is measured by the Visual Analogue Scale on an 11-point Likert scale. Return to work and sports is also recorded. The pressure load of the injured and non-injured ankle is measured by a scale at every visit, starting at 6 weeks.

Post-operative complications are defined as 1) wound healing problems (no interventions required), 2) superficial wound infections (requiring oral antibiotic treatment based on a wound culture), 3) infection near hardware (requiring surgical debridement and intravenous antibiotic treatment based on a deep tissue culture), 4) hardware failure (requiring re-operation), 5) mal-union or non-union (clinically and radiographically confirmed), and 6) deep venous thrombosis (confirmed by ultrasound).

Analysis will be conducted according to the intention-to-treat principle. In bivariable analysis, Pearson’s correlation will be used for continuous variables, Student’s t-test for dichotomous variables such as gender, and ANOVA for categorical variables such as the post-operative care regimen. Multivariate analyses will only be performed post hoc and are considered hypothesis-inducing as opposed to hypothesis-testing and will be ascribed as such.

Participation in this trial does not elicit additional risks besides the standard complications of ankle surgery, such as wound infections, deep venous thrombosis, and hardware failure [12,13]. Although all three post-operative care regimens are independently investigated, unprotected weight bearing by unrestricted mobilization as tolerated has not yet been investigated in a randomized trial. Therefore, strict criteria for premature termination are implemented.

A DSMB has been established. An interim analysis will be conducted after every serious adverse event and after half of the target enrollment is reached. The DSMB consists of two independent physicians and one clinical epidemiologist. The members are not committed to this trial. The DSMB will provide advice that will be disclosed to the Institutional Review Board. The steering committee may terminate the study prematurely if advised by the DSMB. In addition, statistically significant, sufficiently powered, and clinically relevant results during interim analysis may be compelling to terminate the trial prematurely. For this trial, the following termination criteria have been established:

This study will be conducted according to the principles of the Declaration of Helsinki (version 9, October 2008, Seoul) and in accordance with the Medical Research Involving Human Subjects Act. The Verenigde Commissie Mensgebonden Onderzoek (VCMO) approved the study in the St. Antonius Hospital and Diakonessenhuis. The Centrale Commissie Mensgebonden Onderzoek approved the study in Medisch Centrum Haaglanden. The Medisch Ethische Toetsingscommissie approved the study in the St. Elisabeth hospital. Ethical Approval from the Twee Steden hospital was obtained from the board of directors based on VCMO approval.