The protocol will be reported in accordance with the guidelines and checklists for Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT).
Aim, design and setting
We aim to investigate if radiofrequency coblation associated with ESWT can provide more encouraging outcomes regarding the treatment of the IAT with trustworthy evidence.
This study is a randomized, parallel-group clinical trial (Fig. 1). The 1:1 allocation to either receive radial ESWT or sham-ESWT, after surgery is conducted using computer-generated random allocation sequences and sealed envelopes. The patients of placebo group will also experience ESWT’s procedure, while the apparatus’ therapeutic head will be placed a support, which will block the propagation of shock wave without changing equipment’s appearance, noise and using process. Furthermore, the patients will feel the vibration of the machine, but the insertional region won’t be directly stimulated. The physiotherapists will not take any part in the posttreatment assessment of the patients. The outcome data will be collected by research fellows who are blinded to the treatment procedures to reduce the risk of assessment bias. The SPIRIT Figure shows in detail the schedule of enrollment and assessments (Fig. 2).
Characteristics of participants
Patients referred to Department of Sports Medicine, Huashan Hospital, Fudan University with insertional Achilles tendinopathy who had no symptom relief after 3 to 6 months of conservative therapy31 other than ESWT are assessed for eligibility. The diagnosis is based on a medical history and clinical examination including persistent pain at the calcaneus tendon insertion region, and ultrasound or MRI results confirm it.
The inclusion criteria are as follows:
(1) Medical history, clinical examination and ultrasound or MRI results conform to the diagnosis of IAT.
(2) Age 18–65 years, both genders.
(3) The patient has decided to accept percutaneous radiofrequency coblation and radial ESWT.
(4) The patient must be expected to be able to attend post-operation examinations.
(5) The patient must be able to give informed consent.
The exclusion criteria are as follows:
(1) Previous surgery on the affected limb.
(2) The patient would not be able to strictly follow trial procedures or complete questionnaires.
(3) Non-insertional or mixed tendinopathy (insertional and non-insertional).
(4) Pregnancy or intention to be pregnant.
(5) Currently undergoing follow-up and treatment in a psychiatry department or by other mental health professionals.
Participants may decline to continue from the trial at any time without prejudice and still encouraged to keep in touch and welcomed to inquiry and asking for necessary help.
Other reasons for discontinuation include:
(1) The patient develops Achilles tendon rupture.
(2) The patient develops complex or increasing regional pain.
(3) Other unexpected and unpredictable circumstances when the research team judges that the risk of continuing the protocol treatment is greater than the benefit.
The primary outcome for this study is the VISA-A score. McCormack J et al.32 has identified the minimum clinically important difference (MCID) of 6.5 points for the VISA-A. The study of Wei M et al.33 indicates an expected standard deviation (SD) of 6.9 points. We have referred to the sample size calculation method of Kvalvaag, E et al.34 To detect a difference in results between the radical ESWT and the sham-ESWT participants at a level of 5% significance and the most likely scenario for 80% power, 15 patients per group will be needed. Assuming a margin of 20% loss of primary outcome data, we propose to recruit a minimum of 38 patients in total.
A patient is considered to be included in the protocol if he/she meets all of the inclusion criteria and none of the exclusion criteria. Then the patient will be verbally informed of the study and given the opportunity to decide whether he/she wants to participate in the trial on an informed basis without any pressure. Then a written informed consent will be obtained from each participant. Once included, the VISA-A Score, MRI UTE T2* value, FAOS Score, VAS Score, and Tenger Score will be assessed. Within one week after being enrolled, the percutaneous radiofrequency coblation will be performed by an experienced surgeon. After the surgery, each patient will randomly take an unmarked, opaque, sealed envelope containing a piece of paper with a unique number from 1 to 38. Then the numbers will be divided into two sets via computing software (https://www.randomizer.org/). All patients respectively entered the intervention group and the placebo group according to their own numbers. Patients of intervention group will receive ESWT at 6 months post-operatively. At the same time, the patients of placebo group will also experience sham ESWT’s procedure. Either the radial ESWT or sham ESWT will be administered 4 times at weekly intervals. In all, the treatment protocols for the two groups are similar except for the intervention: radial ESWT. All the outcome measurement will be assessed again at 6 months, 1 year, and 2 year after the surgical procedure.
Percutaneous radiofrequency coblation
The symptomatic region will be identified and marked before the anesthesia. Then, the patient would accept general anesthetic and be placed in a prone position. A grid with 5 mm interval will be mapped out over the marked site.35 A 1.5 mm Kirschner wire will be used to puncture the skin and make eyelet-sized holes. The radiofrequency probe (Topaz, ArthroCare, Sunnyvale, California) will be inserted and subsequently activated for 1 second with minimum power, hole by hole. If there exists other concomitant injury such as Haglund deformity, it will be recorded and addressed by endoscopic surgery at the same time. After completion of the procedure, a standard sterile dressing would be applied to minimize tension across the wounds.
Crutch will be recommended during the first 4 weeks after surgery. No immobilization is needed. In addition, all the patients will be encouraged to begin range of motion and isometric strength exercises immediately after surgery, and eccentric training will begin 6 weeks after surgery.36 At 4-week follow-up, the patients will be advised to wear regular shoe gear and continue the exercises. Patients shall be able to walk normally without any assistive device since the seventh week.
Extracorporeal shockwave therapy
Patient will be lying on the stretcher in the prone position with barefoot, and the feet will be positioned towards the shock wave apparatus. The symptomatic area will be marked, then ultrasound gel will be applied on this region which the radial shock waves with a Dolorclast equipment (EMS Electro Medical Systems, Nyon, Switzerland), the intensity being 2000 pulses, 6–8 Hz of frequency, and 1.5–2.5 Bar of pressure per application. Compared with those of radial ESWT group, patients of sham ESWT group will go through the same process with the same equipment, in which the apparatus’ therapeutic head will be installed a support. The support will block the propagation of shock wave without changing equipment’s appearance, noise and using process. Furthermore, the patients will feel the vibration of the machine, but the insertional region won’t be directly stimulated. Either the radial ESWT or sham ESWT will be administered 4 times at weekly intervals.
Patients will be positioned feet first-supine and both feet are placed simultaneously in the dorsal part of the head coil then will be examined in a 3.0 T horizontal magnet (Discovery MR750, GE Medical System, Milwaukee, WI). For morphological evaluation of the Achilles tendon, three-dimensional fat-saturated proton-density-weighted turbo-spin echo (PDTSE) will be used. Other parameters were set as follows: repetition time (TR) = 202.1 ms, field of view (FOV) = 140 mm× 140 mm,slice thickness (ST) = 2 mm. Four echo time images (TE = 0.032, 7.5, 20.5, and 28 ms) will be obtained. T2* value of Achilles tendon insertion region is calculated by fitting the acquired signal at different echo time to a single exponential decay model.
Victorian Institute of Sports Assessment Achilles (VISA-A) Score
The VISA-A score is a validated questionnaire for Achilles tendinopathy and contains 8 questions assessing physical activity and pain (0, no activity/maximum pain; 100, maximum activity/no pain).34 And it is adapted to the local language (Attachment 1). The Chinese version has been used in clinical trials37 38, proving its validity.
(1) MRI: UTE-T2* value
The MRI UTE-T2* has been reported to show the significant differences between Achilles tendinopathy and normal tendon.27–29 Thus, the morphological information of tendon after treatment could be monitored.
(2) Foot and Ankle Outcome Score (FAOS) scale
(3) Visual Analogue Scale (VAS)
(4) Tegner Score
All relevant data will be collected by research fellows who are blinded to the treatment procedures and recorded in specially designed case report files. The patients will be identified by an assigned number. At the completion of the study, all identifiable data will be destroyed. The patients are informed, both verbally and in writing, that data are stored and analyzed in a computer, that the patient ’s anonymity is preserved, and that the data protection legislation is adhered to.
Adverse event management
Achilles tendon rupture is presumably a complication of both the percutaneous radiofrequency coblation and the ESWT treatment, therefore the number of Achilles tendon ruptures will be registered. Furthermore, an adverse event is defined as any unintended, unfavorable finding, symptom, or disease that occurs, whether it is considered to be related to the study or not. Adverse events will be recorded. Serious adverse events (SAEs) is defined as an event or reaction which will cause death, life-threatening situations, hospitalization or prolongation of existing hospitalization, or permanent or severe disability. SAEs will be reported to the ethics committee within 24 hours.
End of trial
The end of the trial will be defined as the collection of 2 years outcome data from the last participant.
All continuous data from primary and secondary outcome measurements will be summarized by descriptive statistics with the number of observations (n), mean, SD, minimum, median and maximum. Uncontinuous data such as co-morbidities concomitant injuries will be summarized by descriptive statistics with the number of observations, calculating the incidence separately and analyze whether it is associated with prognosis. The primary point for analyses of efficacy will be 6 months after surgery, then 1 year and 2 years. A statistical software program (SPSS for Windows, version 23.0; SPSS Inc, Chicago, Illinois) will be used for statistical analysis in this study. Group comparison will be statistically analyzed by either the Student’s t test or the Mann–Whitney U test, depending on whether the data is normally distributed. The significance level will be set at a p value < 0.05.
Patient and Public Involvement
Neither patients nor the public were involved in the design of the study, including conceiving the research questions and deciding the outcomes. However, all participants will be asked whether they would like to receive a copy of the trial results at the time of consent. Once completed the trial, a copy of the personal results will be emailed to participants who said yes. Also, the burden of the intervention will be assessed by participants themselves using a questionnaire39 40.