Objectives and hypotheses
The objective of this prospective randomized controlled single-center study is the comparison of gait analysis, clinical and radiographic outcome after stabilization of an acute syndesmosis rupture with either a static implant (a 3.5mm metallic screw through three cortices) or a dynamic device (TightRope®).
The following hypotheses will be tested:
H0: The biomechanical (regarding ankle range of motion and maximum plantar flexion power in the gait analysis), clinical (study questionnaire, SF-12, OM, VAS, FAOS) and radiological outcome is different in both treatment options.
H1: The biomechanical (regarding ankle range of motion and maximum plantar flexion power in the gait analysis), clinical (study questionnaire, SF-12, OM, VAS, FAOS) and radiological outcome is equal in both treatment options.
Patients with acute syndesmosis rupture (isolated or combined), suitable according to the study protocol, will be randomized to the two different treatment options (screw fixation or TightRope®).
Syndesmosis reduction will be assessed using CT/3D imaging intraoperatively with ISO C 3D or CIOS Spin (Siemens Healthineers GmbH, Erlangen, Germany) as a part of our standard procedure.
6 Months after the initial treatment, the patients will receive an additional gait analysis and a MRI in the follow-up examination at our outpatient clinic.
Study design, registration and ethics
The study protocol was conducted according to the Declaration of Helsinki and approved by the local ethical committee of our hospital (S-454/2017). Furthermore, it was registered at the German Clinical Trials Register (DRKS00013562).
This study is a registered, clinical, prospective, randomized, controlled, single-center, two-arm, parallel group trial with a one-year follow-up, carried out at a level 1 trauma center.
Inclusion and exclusion criteria
Patients older than 18 years who suffer from acute syndesmosis rupture and who are undergoing surgery for a syndesmotic rupture at our Center for orthopedics and trauma surgery will be included in this study after giving their informed consent.
Exclusion criteria are pregnancy, the disability for approval, congenital deformities of the lower extremities, missing informed consent or refusal of participation. Patients with any known contraindications for MRI examination will be excluded as well.
Study setting and population
Study patients pass a follow-up over one year with clinical and radiologic examinations one day before and after the initial operation as well as 6, 12, 26 and 52 weeks after treatment in our outpatient clinic. In this study there is no need for additional clinical examinations for the patients, with the exception of an additional motion analysis and a MRI 6 months after initial treatment to evaluate the biomechanical outcome and the healing status of the syndesmosis ligament.
Surgery and examinations will be performed by an experienced orthopedic and trauma surgery consultant.
The patients will be randomized to the different treatment options (screw fixation or TightRope®).
The following questionnaires will be used for clinical and psychosocial evaluation:
"study questionnaire screw vs. TightRope"
"SF-12 – Health survey"
"Score of Olerud und Molander (OMAS)"
"pain on a VAS"
"Foot and ankle outcome score (FAOS)"
In the following, the procedure of this study is described and additionally illustrated in
- Diagnosis of an acute syndesmosis rupture (isolated or combined) and indication of surgical treatment in our clinic
- Informed consent and inclusion
- Randomization 1:1 to the different treatment options (screw fixation or TightRope®)
- Preoperative clinical and radiologic examinations
- Preoperative clinical and psychosocial evaluations with questionnaires above-mentioned
- Surgery with screw fixation or TightRope®
- Standardized intraoperative CT/3D imaging with ISO C 3D or CIOS Spin (Siemens Healthineers GmbH, Erlangen, Germany) for assessment of syndesmosis reduction
- Postoperative clinical and radiologic examinations with x-ray of foot and ankle
- Clinical and radiologic follow-up (6 weeks, 3, 6, 12 months) postoperatively + abovementioned questionnaires
- additional standard clinical instrumented 3D gait analysis to evaluate the biomechanical outcome (duration: 30 minutes) 6 months after the operation
- additional MRI of the ankle joint to evaluate the healing status of the syndesmosis ligament (duration: 30 minutes) 6 months after the operation
Participants and consent
All patients assigned for surgical treatment of acute syndesmosis rupture at our level 1 trauma center can be involved in our study. Patients must be at least 18 years of age without any exclusion criteria and provide their written consent before any study-relevant intervention. Before participation, each patient, suitable to the study protocol, will be fully informed by informed consent about the scientific purpose and risks associated with the procedures. The participation is voluntary and every participant is able to withdraw their consent to participate in the trial at any time without giving reasons.
Informed consent takes place in an one-to-one appointment at trauma center with an experienced orthopedic and trauma surgeon. A full verbal explanation of the study, a written patient information sheet and informed consent form will be provided before inclusion.
Patients will be randomly assigned to one of two groups (intervention or control) using a computer-generated random block assignment in a 1:1 ratio using nQuery Advisor v7.0 software (Statsols, Cork, Ireland). This method helps in maintaining the balance of treatment assignment while reducing the potential for selection bias. Patients, researchers performing the follow-up examination and the trial statistician will be blinded to the group allocation. If the treatment of syndesmosis rupture is not accomplished after randomization due to an intraoperatively observed missing acute syndesmosis rupture with no need of stabilization, the patient will be excluded from final analysis. At the date of screw removal 6 to 8 weeks after the operation, a blinding of the patients will no longer be possible.
The fractures will be fixed within 8 days of the initial trauma in both groups using standard AO (Arbeitsgemeinschaft für Osteosynthesefragen) (17) principles. Antibiotic prophylaxis will be given perioperatively. Open reduction and internal fixation (ORIF) of fibula fractures will be treated either with a 1/3 tubular plate with or without lag screws or in high fibula fractures with syndesmosis fixation only. Additional fractures of medial and/or posterior malleolus will be treated according to standard principles before stabilizing the syndesmosis. The distal tibio-fibular joint will be reduced without direct visualization of the syndesmosis and held at its anatomical position by a reduction clamp. The ankle joint will be positioned at an angle of 90° between the tibial shaft and the foot during syndesmosis fixation in accordance with the randomization (cortical screw or TightRope®).
For the static syndesmotic screw fixation, a 2.5 mm hole will be drilled under fluoroscopic guidance, approximately 2 cm above and parallel to the distal tibial joint line from lateral to medial. If plating of the fibular fracture is necessary, the hole will be drilled through an empty screw hole. Three cortices will be drilled through and a 3.5 mm screw will be tightened.
For the dynamic fixation of the Syndesmosis by means of TightRope® a 3.5 mm hole will be
drilled under fluoroscopic guidance, approximately 2 cm above and parallel to the distal tibial joint line (through a hole of the plate if present) from lateral to medial. A guide needle will be inserted from lateral to medial through the drill hole to position the oblong button over
the medial tibial cortex and confirmed by x-ray. Afterwards, the assembly will be tensioned by pulling the free ends of the FiberWire on the lateral side. These will be hand-tied with a surgical knot and the round button will be firmly applied on the lateral cortex of the fibula (or onto the plate if present). After achieving an adequate syndesmotic fixation by either technique, the reduction clamp will be removed and the stability controlled under fluoroscopy.
After syndesmosis fixation, intraoperative CT/3D imaging with ISO C 3D or CIOS Spin (Siemens Healthineers GmbH, Deutschland) will be performed to evaluate syndesmosis reduction.
The post-operative treatment protocol is similar in both groups. The ankle will be immobilized in a below-the-knee cast with the ankle joint at 90° for 6 weeks with partial weight-bearing. Between the 6th and 8th week, only the static syndesmosis screw will be removed in a standardized outpatient surgery. The dynamic fixation of the syndesmosis by means of TightRope® needs no removal postoperatively. Afterwards, weight-bearing can be gradually increased with approximately 20 kilograms per week until full weight-bearing is achieved.
Subsequent to surgery, all patients will receive similar follow-up procedures. Follow-up at our trauma center is standardized, based on a well-established protocol, and all procedures and diagnostics are based solely on medical indications. First radiological and clinical evaluation of the surgical treatment will be performed on day two after surgery. Discharge from hospital will be realized as soon as general health conditions (soft tissue conditions, patient mobility and pain level) allow it. Afterwards, patients will receive physiotherapy and manual lymphatic drainage. Further clinical and radiographic evaluations are planned for 6 weeks, 3, 6 and 12 months after surgery following our standardized procedure for fracture patients treated in our hospital (tab. 1). There are no additional follow-up appointments or x-ray examinations necessary for the study. Merely the gait analysis and MRI control of the syndesmosis will be performed 6 months postoperatively during the regular follow-up appointment.
MRI images will be assessed by a senior radiologist for degenerative changes of the tibio-talar joint and the syndesmosis structure (unaffected, hyperintense signal alteration on T2, partial tear, complete tear), widening and calcification. By using questionnaires preoperatively and postoperatively after 6 weeks, 3, 6, and 12 months during the appointments, patients can provide information on pain, mobility of foot and ankle and quality of life (SF-12) (18) during the course of treatment. General patient data, including age, profession, Body Mass Index (BMI), risk factors, medication, concomitant diseases, previous surgeries and details of the accident will be documented preoperatively.
At 25 weeks postoperatively, patients also receive a gait analysis and MRI is performed to assess motion anomalies and the healing process of the syndesmosis.
The planned study will run over two years. Patients will be admitted over a period of one year. Each patient will be treated and followed-up over a twelve-month period.
All data will be stored and monitored using pseudonyms. The data of all patients will be analyzed statistically and compared at the end of the two years (tab. 1).
Furthermore, all data of the participating patients will be carefully assessed, and all adverse events and complications of the treatment will be reported at the end of this trial. The harms will be categorized according to their degree of severity in either serious or non-serious.
Tab. 1: Overview of clinical and radiologic follow-up
CT – computed tomography, MRI – magnetic resonance imaging, SF-12 – 12-item Short Form health survey, VAS pain - Visual Analog Scale for Pain
Criteria that lead to termination of study
Every participant is able to withdraw their consent to participate in the trial at any time without giving reasons. Thereby the recorded study data may be destroyed immediately upon request or with the consent of the participant, can still be included in the evaluation.
If initial data indicates either impossible realization due to technical difficulties or an increased risk for the participants that is potentially harmful, the study will be terminated immediately.
Sample size calculation and statistical analyses
Formal sample size determination is not possible as potential effects are not yet known. Data from previous studies were utilized to determine the necessary sample size (19-21). We plan a sample size of 25 patients, who will be treated with the cortical screw fixation and 25 patients, who will be treated with the dynamic TightRope® system within two years. The patients will be randomized to the two different treatment options. The randomization will be independent of the surgeon and the doctor who will do the examinations and the questionnaires.
Standard unpaired Student's t-test and ANOVA-test to detect significant changes between the two groups will be conducted.
The empirical distribution of continuous data and scores will be reported and calculated with means, standard deviation (SD), median, minimum, maximum values and with absolute and relative frequencies for categoric data as well as unpaired t-test p-values to depict a significant difference between the different groups. An independent senior statistician of the Institute of Medical Biometry and Informatics of our university will perform the analysis.
The analysis and illustrations will be carried out by use of SPSS version 25.0 for 135 Windows (IBM Corp., Armonk, New York, USA) and GraphPad Prism version 6.00 for Windows (GraphPad Software, San Diego, California, USA). Categorical variables will be examined for differences using the chi-square test. Possible differences for continuous data and scores between groups will be evaluated with the Wilcoxon U-test. For the representation of statistical relationships, the Pearson correlation coefficient will be used. The final details of the statistical analysis will be established in a statistical analysis plan, which will be completed before the closing of the database (before the end of data collection). A p-value of ≤.05 will be used to indicate statistical significance.
Primary outcome measures
The primary endpoint of this study is a successful healing of the syndesmosis 6 months after surgery by evaluation of MRIs of the ankle (22). MRI scanning in the plain of the syndesmotic ligaments is the investigation of choice to evaluate syndesmosis healing. MRI images will be evaluated for degenerative changes of the cartilage of the ankle, appearance (unaffected, hyperintense signal alteration on T2, partial/complete tear), widening and calcification of the syndesmosis. If these evaluations are ordinary, successful healing can be assumed.
Another primary outcome measurement of this study is the gait analysis 6 months postoperatively to detect biomechanical differences between both treatment groups.
Due to the pilot study character, it remains to be clarified which are the most suitable parameters to depict potential effects and differences.
Secondary outcome measures
Secondary endpoints and measurements will be recorded 6 weeks, 3, 6 and 12 months postoperatively. The measurements include different questionnaires mentioned above with subjective evaluation of the quality of life (assessed by the 12-item Short Form health survey [SF-12] questionnaire) (18), pain (Visual Analog Scale [VAS]). In addition, a self-designed questionnaire as well as the “Score of Olerud und Molander (OMAS)" (23) and "Foot and ankle outcome score (FAOS)" (24) will be used to evaluate the range of motion, deficits in daily life, symptoms after ankle fractures and after surgical treatment and socioeconomic factors (period of time, returning back to work and time of recovery).