Study design
This study was designed as a prospective randomized controlled trial comparing 2-octyl cyanoacrylate TSA and n-octyl cyanoacrylate TSA for wound closure after ankle fracture surgeries using a 1:1 randomization. After approval by the local ethics committee (Korea University Guro Hospital Institutional Review Board, 2018GR0099), the study was registered in the Clinical Research Information Service (https://cris.nih.go.kr) database, which is a non-profit online registration system for clinical trials established by the Korea Disease Control and Prevention Agency.15 All study protocols were conducted in accordance with the Consolidated Standards of Reporting Trials guidelines.16
Inclusion/exclusion criteria
Patients who required open reduction and plate fixation for isolated lateral malleolar fractures were included. Among the patients with rotational ankle fractures, those with associated posterior malleolar fractures or a partial deltoid ligament rupture but only required open reduction and plate fixation for the lateral malleolar fracture were also included. The exclusion criteria were as follows: (1) < 18 or > 65 years of age; (2) previous surgeries at the ankle joint; (3) significant medical comorbidities potentially affecting wound healing (e.g., end-stage renal failure, peripheral vascular disease),17,18 (4) history of keloid formation, open fracture, or other notable skin injuries around the ankle joint combined with fracture; (5) blistering on the incision site; (6) > 10% of ankle edema in the injured side compared to the uninjured side measured by the figure-of-eight-20 method,19 (7) workers’ compensation, and (8) participation in another study. Among the eligible patients, those who provided informed consent for participation were finally included.
Participants
Between April 2018 and May 2021, 342 patients visited our institution for rotational ankle fracture, and 78 patients met the inclusion/exclusion criteria. Of these patients, 22 were excluded because they did not wish to participate in the study, leaving 56 patients randomized into both groups (Fig. 1). The full date of the first registration was 20/08/2021, and the registration number was KCT0006476.
Randomization
Patients were randomly assigned to one of the two groups using sequentially numbered opaque-sealed envelopes made by the study coordinator. The randomization sequence was constructed using computer software (Excel 2016; Microsoft, Redmond, WA, USA).20 Neither the patients nor the surgeons knew the randomization outcomes until the day of surgery.
Preoperative assessment
Preoperatively, 3 to 7 days of bed rest and elevation of the injured ankle were performed to reduce swelling to an acceptable level for internal fixation. To quantify preoperative soft tissue swelling at the incision site, both ankles were measured using the figure-of-eight-20 method.19 The percentage of measured edema on the injured side was calculated as a fraction of the edema of the injured side to that of the uninjured side, and this value was used to identify intergroup differences.
Interventions
Open reduction and plate fixation of the fractures were performed by a single surgeon on the basis of standard AO principles.21 Closure of the fascial and subcuticular skin layers was performed in the same way in both groups using 2 − 0 and 3 − 0 synthetic absorbable braided sutures (Vicryl Plus, Ethicon Ltd, Edinburgh, UK). Either 2-octyl cyanoacrylate TSA (Dermabond Prineo, Ethicon, Somerville, NJ, USA) or n-butyl cyanoacrylate TSA (LiquiBand, Advanced Medical Solutions, Winsford, UK) was then applied in two thin layers with a drying time of 30–60 s between layers to enable polymerization. In the 2-octyl cyanoacrylate group, this process was performed over the contained polyester mesh according to the manufacturer’s instructions. A standard absorbent dressing was then applied and changed on the second day after surgery.
Primary and secondary outcomes
As a validated wound assessment tool, the Hollander wound evaluation scale (HWES) was used as a primary outcome measure. The HWES consists of five subscales, and the wounds with a score of 6 were considered to have an optimal cosmetic appearance: step-off of borders (edges not on the same plane; 0 for yes, 1 for no), contour irregularities (wrinkled skin near the wound; 0 for yes, 1 for no), margin separation (gap between side; 0 for yes, 1 for no), edge inversion (wound not properly everted; 0 for yes, 1 for no), excessive distortion (swelling/edema/infection; 0 for yes, 1 for no), and overall appearance (subject appearance: 0 for poor, 1 for acceptable).22,23 The assessment of HWES was independently performed by two orthopedic surgeons, and in cases of disagreement between them, the final decision was made via consensus.
Secondary outcome measures included the visual analog scale (VAS) and 5-item Likert scale to assess patient satisfaction with wound cosmesis. The VAS score was determined by measuring the distance (mm) on the 10-cm line between the “worst possible scar” anchor and the patient mark, providing a range of scores from 0 to 100.24,25 On a 5-point Likert scale, patients were asked about their satisfaction with wound cosmesis in one of the following items: very unsatisfied, unsatisfied, neutral, satisfied, and very satisfied.26 The HWES, VAS, and 5-point Likert scale were assessed at 3 and 6 months of follow-up visits. To reduce the bias of outcome due to the incision length, the incision lengths were measured to investigate whether there was a difference between the two groups.
Additionally, the Olerud–Molander ankle score (OMAS; scale, 0–100 points) was assessed at 6-month follow-up visits to measure the functional outcome. A higher OMAS indicates better outcomes and fewer symptoms.27
Blinding
A single-blinded study design was used. Surgeons and patients were not blinded to group allocation. Outcome assessments and statistical analyses were performed by one author who did not participate in the operative procedures and was blinded to the allocations.
Sample size calculation
The non-inferiority trial method was used to determine the appropriate sample size.28 Using the HWES at 6 months postoperatively as the primary outcome of measure, the sample size was calculated to have a power of 80% and a significance level of 0.05. To determine whether the 2-octyl cyanoacrylate TSA was not inferior to the n-butyl cyanoacrylate TSA, 25 patients per group were required to have 80% power that the lower limit of a one-sided 95% confidence interval for the difference between two treatments would be above the non-inferiority margin of -1.0 point (standard deviation, 1.25 points). Since there was no universally established minimal clinically important difference for the HWES, the non-inferiority margin was selected by investigators on the basis of a previously conducted prospective study.29 Adding an assumed dropout rate of 10%, 28 patients were finally enrolled in each group.
Statistical analysis
The Kolmogoro–Smirnov test was used to determine data normality. The independent t-test or Mann–Whitney U test was used to compare the following continuous variables: age, body mass index (BMI), HWES score, VAS score, OMAS, and incision length. The chi-squared test or Fisher’s exact test was used to compare the following categorical variables: sex, smoking status, diabetes, injury mechanism, and 5-point Likert scale score. Inter-observer reliability for the HWES was assessed by calculating the kappa coefficient (κ), and the values were judged as follows: poor (< 0.0), slight (0.01–0.20), fair (0.21–0.40), moderate (0.41–0.60), substantial (0.61–0.80), and almost perfect (0.81–1.00).30 All statistical analyses were performed using SPSS (version 23.0; IBM Corp, Armonk, NY), with statistical significance set at p < 0.05.