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Trial registered on ANZCTR


Registration number
ACTRN12619001455156
Ethics application status
Approved
Date submitted
4/10/2019
Date registered
22/10/2019
Date last updated
11/04/2024
Date data sharing statement initially provided
22/10/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Efficacy of Tendon Strip Injections compared to sham following failure of conservative therapy for Achilles tendinopathy
Scientific title
Efficacy of Tendon Strip Injections compared to sham following failure of conservative therapy for Achilles tendinopathy
Secondary ID [1] 299469 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Achilles Tendinopathy 314689 0
Condition category
Condition code
Musculoskeletal 313036 313036 0 0
Other muscular and skeletal disorders
Injuries and Accidents 313105 313105 0 0
Other injuries and accidents

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
A single TSI or sham injection will be delivered by a radiology nurse and experienced musculoskeletal radiologist.Three injection groups
(i) Tendon strip injection with steroid: The TSI consists of five syringes, the first with exactly 10 mL of 0.5% bupivacaine hydrochloride and 25 mg of hydrocortisone (the syringe will be large enough to take both the local anaesthetic and steroid), followed by four syringes with 10 mL each of normal saline. The TSI will be injected into the interface between Kager’s fat and the Achilles tendon. The local anaesthetic + the steroid, followed by the four saline syringes are injected consecutively by using a connecting tube (allows consecutive syringes to be attached). The position of the needle is monitored continuously by ultrasound and the needle is moved gently across the anterior aspect of the tendon to ensure uniform effect over the pathological area. Including our preliminary trials and the prior case series on TSI there are over 175 participants who have had this procedure, with no reports of serious complications (e.g. tendon rupture, infection).
(ii) Tendon strip injection without steroid: This injection is identical to the TSI with steroid, but the first syringe will only contain exactly 10 mL of 0.5% bupivacaine hydrochloride (no steroid).
(iii) Sham injection: The sham injection consists of five syringes like the tendon strip injection. The first contains 2-3 mL of 0.5% bupivacaine hydrochloride. The subsequent four syringes contain 0.25mL of normal saline (i.e a few drops). Total volume is 3-4mL. The sham will be injected under image guidance by the same expert radiologist, deep to the tendon and away from the interface between Kager’s fat and the Achilles tendon (at last 5mm away). The sham injection will result in a numbing effect, like the TSI. Immediately post injection participants will be asked which injection they believe they received to assess the success of participant blinding.
Post injection treatment:
Immediately after the injection, participants will be asked about how logical and successful they feel the treatment they have received will be, as well as their confidence in the treatment. This will only be assessed at the baseline.
After the injection, an appropriately trained researcher, who is blind to treatment allocation will deliver identical advice and a 12-week exercise program to all participants, based on our prior TSI work. This includes an evidence-based and progressively loaded exercise protocol for Achilles tendinopathy, education about physical activity modification and resumption, and advice about progressing and regressing exercise load, based on a pain monitoring model. The researcher will also provide education about Achilles tendinopathy (pathology, pain, risk factors, prognosis, treatments, recovery times). Participants will be reviewed by the researcher at 2, 6 and 12 weeks (all at at Imaging at Olympic Park (IOP), aside from week 2 over Zoom) to modify the exercise as required (e.g. progress load, modify technique), and at 12 weeks to provide evidence-based advice about continuing exercise beyond the intervention period. The researcher will also call participants at week 1, 4,8 and 10 to ask whether they have any questions or issues with the exercise or education intervention, and participants will be provided with basic online exercise videos and education and the researchers contact details that they can use at any time. Participants will be advised to refrain from using other physical therapy interventions and non-steroidal anti-inflammatory medications but will be allowed to take paracetamol (up to 4g/day) for pain relief as required.

Details of the exercise program:
a) who is administering the program: physiotherapist for first 12 weeks and self-administered after that.
b) the mode of administration: independently at home.
c) the level of intensity: will be adjusted by the participants themselves. They will be advised to do 15 repetitions x 4 sets, once a day for three times a week. If they experience less than 5/10 pain and have 2 reps in reserve, then they will be advised to add weights in 5kgs increments.
d) the frequency/duration of program, 15 repetitions x 4 sets, once a day for three times a week for 52 weeks.
Participants will be reviewed by the researcher at Imaging at Olympic Park (IOP) at 2, 6 and 12 weeks to modify the exercise as required (e.g. progress load, modify technique), and at 12 weeks to provide evidence-based advice about continuing exercise beyond the intervention period.

Details of the education program:
a) who administers the education: physiotherapist for first 12 weeks and participant self-administered after that.
b) the mode of administration: videos, education leaflets.
c) the frequency/duration of program: single session at the beginning of the program and then follow up calls at week 1, 4,8 and 10 to ask whether they have any questions or issues with the exercise or education intervention.

Participants will also be reviewed by the researcher at Imaging at Olympic Park (IOP) at 2, 6 and 12 weeks to modify the exercise as required (e.g. progress load, modify technique), and at 12 weeks to provide evidence-based advice about continuing exercise beyond the intervention period.

The education/exercise relative to the injection procedure: The education will be delivered on the same day post-injection, and participants will be advised to start the exercises 2-3 days post-injection.

strategies to monitor adherence: participants will be advised to maintain an exercise diary to log their attendance every time they perform exercises. The physiotherapist/research assistants will also make follow up calls at week 1, 4,8 and 10 to ask whether they have any questions or issues with the exercise or education intervention. Participants will also be reviewed by the researcher at IOP at 2, 6 and 12 weeks to modify the exercise as required (e.g. progress load, modify technique), and at 12 weeks to provide evidence-based advice about continuing exercise beyond the intervention period.
Intervention code [1] 315722 0
Treatment: Drugs
Intervention code [2] 315723 0
Treatment: Other
Comparator / control treatment
Sham injection: The sham injection consists of five syringes like the tendon strip injection. The first contains 2-3 mL of 0.5% bupivacaine hydrochloride. The subsequent four syringes contain 0.25mL of normal saline (i.e a few drops). Total volume is 3-4mL. The sham will be injected under image guidance by the same expert radiologist, deep to the tendon and away from the interface between Kager’s fat and the Achilles tendon (at last 5mm away). The sham injection will result in a numbing effect, like the TSI.
Control group
Placebo

Outcomes
Primary outcome [1] 321587 0
Primary outcome: Pain and function will be assessed with the VISA-A, a well validated, reliable and disease-specific tool. This outcome includes pain, function and activity domains that are clinically relevant to patients with Achilles tendinopathy. Scores range from 0 to 100, with 100 indicating no symptoms or function/activity limitations.
The final two question of the VISA-A were designed for sporting populations and will be modified in our study to relate to our mixed sporting and non-sporting population. Question 7 will be modified from ‘Are you currently undertaking sport or other physical activity?’ to ‘Are you currently undertaking sport or other physical activity, including walking?’. Question 8 asks about pain and disability during Achilles tendon loading sport. ‘Achilles tendon loading sport’ will be changed to ‘weight-bearing activity’. Both versions of question 8 will be included so that responsiveness of both versions of the VISA-A can be evaluated.

It's a composite primary outcome.
Timepoint [1] 321587 0
baseline, 6, 12, 26 and 52 weeks
Secondary outcome [1] 375496 0
Achilles tendon thickness and Doppler signal: An experienced musculoskeletal ultrasonographer blind to treatment allocation will assess Achilles tendon thickness and Doppler signal (a marker of the degree of neurovascular ingrowth) on ultrasound imaging using reliable methods. Doppler signal will be assessed by quantifying pixel count.

It's a composite secondary outcome.
Timepoint [1] 375496 0
Baseline, 6 and 52 weeks
Secondary outcome [2] 375508 0
The Global Rating of Change Scale (GROC) is an 11-point scale in which the participant is asked to rate their perceived overall change in their Achilles tendinopathy condition from the time that they began the study until the present, as Worse, No Change, or Better. If they indicate worse, the patient will then be asked how much worse on a five-point scale from Very Much Worse to Slightly Worse, and if they are better, they will be asked how much better on a five-point scale from Slightly Better to Very Much Better.
Timepoint [2] 375508 0
6, 12, 26 and 52 weeks
Secondary outcome [3] 375509 0
Overall pain intensity: Measured using the 100 mm visual analogue scale (VAS), participants will rate the worst pain during the last week (zero = no pain; 100 = worst pain possible).
Timepoint [3] 375509 0
baseline, 6, 12, 26 and 52 weeks
Secondary outcome [4] 375510 0
Health-related quality of life: Measured with the EuroQol 5D-5L, a validated and reliable tool, including five domains (mobility, self-care, usual activities, pain/discomfort and anxiety/depression), and a rating of overall health state from 0 (worst health state imaginable) to 100 (best imaginable health state) using a VAS.
Timepoint [4] 375510 0
baseline, 6, 12, 26 and 52 weeks
Secondary outcome [5] 375511 0
The level of physical activity in the previous week: Evaluated using the 7-day Recall Physical Activity Questionnaire, a valid and reliable tool. Participants will be asked to recall time spent sleeping and doing physical activity (work, leisure, household activities) over the past 7 days.
Timepoint [5] 375511 0
baseline, 6, 12, 26 and 52 weeks
Secondary outcome [6] 375512 0
Fear avoidance: The Tampa Kinesiophobia Scale is a validated questionnaire used to measure fear-avoidance.
Timepoint [6] 375512 0
baseline, 6, 12, 26 and 52 weeks
Secondary outcome [7] 375513 0
Maximal voluntary isometric contraction (MVIC): Seated calf raise maximal voluntary isometric contraction (MVIC). Standard strength (MVIC) tests will be performed on a custom chair equipped with a force plate that measures plantarflexor force. Participants will have an adequate warm up (>5 minutes of cycling at a moderate intensity, based on a reported Borg Scale rating of perceived exertion of 6-7/10) and then perform 4 practice and 2 recorded trials. The instructions will be 'push as hard and fast as possible'. It's a composite secondary outcome.

Update: We will report data for maximal voluntary contraction but not rate of force development.
Timepoint [7] 375513 0
baseline, 6, 12, 26 and 52 weeks
Secondary outcome [8] 375514 0
Adverse event: An adverse event is defined as any unfavourable or unintended diagnosis, sign, symptom, or disease associated with the study which may or may not be related to the intervention (e.g. tendon rupture, fall, injury, or change in medical status).
It will be measured using an Adverse events questionnaire, which was designed specifically for this study.
Timepoint [8] 375514 0
Every 6 weeks from week 6 to 52 via online questionnaire (if not coinciding with an assessment visit time).
Secondary outcome [9] 375729 0
Catastrophising: The Pain Catastrophising Scale is a validated questionnaire used to measure pain catastrophisation..
Timepoint [9] 375729 0
baseline, 6, 12, 26 and 52 weeks
Secondary outcome [10] 376963 0
Pain self efficacy: Assessed with the pain self-efficacy questionnaire (PSEQ). The PSEQ measures how confident a patient is in undertaking a range of activities despite their pain.
Timepoint [10] 376963 0
baseline, 6, 12, 26 and 52 weeks
Secondary outcome [11] 376964 0
Healthcare use: Participants will be asked to answer yes or no to whether they have used any health services or co-interventions over the last 6 weeks. If yes we then ask about health professionals seen and how many sessions. We also ask if they had trialled any other treatments. We asked these questions every 6 weeks during the trial.
Timepoint [11] 376964 0
Every 6 weeks from week 6 to 52 via online questionnaire (if not coinciding with an assessment visit time).
Secondary outcome [12] 376965 0
Healthcare use: Medicare Benefits Schedule and Pharmaceutical Benefits Schedule data will be extracted to measure use of subsidised healthcare services.
Timepoint [12] 376965 0
At 12 months for the preceeding 12 months
Secondary outcome [13] 376966 0
Productivity (including absenteeism and presentism) will be measured using the ‘iMTA Productivity Cost Questionnaire’.
Timepoint [13] 376966 0
We modified the outcome measurement time to every 6 weeks.
Secondary outcome [14] 376967 0
Exercise adherence: Participants will record the number of exercise sessions completed on average each week over the previous 6 weeks
Timepoint [14] 376967 0
Every 6 weeks from week 6 to 52 via online questionnaire (if not coinciding with an assessment visit time).

Eligibility
Key inclusion criteria
• Previously trialled first line recommended treatment
• Aged 18 years or above
• more than 3 months of pain in the mid-portion Achilles area proximal to the Achilles
tendon insertion in the calcaneum)
• Primary complaint of mid-portion Achilles pain on one or both lower limbs
• VISA-A <75 points
• Clinical diagnosis of mid-portion Achilles tendinopathy based on the following
criteria:
o Gradual onset pain in the relevant area;
o Midportion Achilles pain during or after Achilles tendon loading activities (e.g. walking, running)
• Ankle joint examination, and especially passive plantar-flexion is essentially normal,
• Confirm diagnosis with ultrasound imaging of the Achilles tendon. One or more of the
following features present in the mid-portion area: (i) hypoechoic regions; and/or (ii)
Doppler signal indicative of vascularisation.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Previous Achilles tendon surgery in the symptomatic lower limb(s)
• Previous Achilles tendon rupture in the symptomatic lower limb(s)
• Other ankle conditions including impingement syndrome, insertional Achilles tendinosis,
Achilles paratenonitis without tendinopathy
• Tendinopathy caused by inflammatory conditions (e.g. ankylosing spondylitis)
• Neurological disorders (i.e. Parkinson’s syndrome, stroke)
• Inherited connective tissue disorders (i.e. Ehlers- Danlos syndrome, Marfan’s syndrome)
• Use of fluoroquinolone antibiotics within the previous two years
• Injection of local anaesthetic, corticosteroid, platelet rich plasma or other pharmaceutical agent into the Achilles tendon or surrounding area within the previous three months
• Any medical and/or social reason that, in the opinion of the investigators, makes the participant unsuitable for inclusion
• Serious mental health problem that would preclude adherence to study or treatment protocols
• Known allergies or hypersensitivity to the study drugs
• Needle phobia or a blood clotting disorder

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
allocation will involve contacting the holder of the allocation schedule who was "off-site" or at central administration site.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
- Simple randomisation using a randomisation table created by computer software (i.e. computerised sequence generation)
- Permuted block randomisation
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Statistical methods / analysis
A Statistical Analysis Plan (SAP) will be completed by AI Forbes (Biostatistician and Chief Investigator on 12 NHMRC grants in the last 5 years). In participants with bilateral symptoms, the most painful side will be analysed (or the right foot if they cannot define the more painful foot) to maintain independence of data. Statistical tests will be two-tailed with statistical significance level set at 0.0167 for each of the 3 pairs of comparisons of trial arms. All randomised patients will be included in the analysis (i.e. intention-to-treat) for primary and secondary outcomes (except for safety outcomes). Demographic characteristics (e.g. age, gender) and other baseline measurements (e.g. duration of symptoms) will be reported by treatment arm. Between group differences in the primary and secondary outcomes measures will be compared at 12, 26 and 52 weeks, with the primary outcome being at 52 weeks. Continuously-scored outcome measures will be analysed using linear mixed models with adjustments for baseline scores and variables that influence the outcome (e.g. age). Ordinal scaled data will be analysed using non-parametric tests and modelled with proportional odds regression adjusted for repeated assessment of subjects. Dichotomous scaled outcome measures will be compared using relative risk, risk difference, and number needed to treat (NNT) using generalised estimating equations. Sensitivity to missing data will be assessed using multiple imputation models incorporating predictive baseline and post-baseline variables.
Economic analysis
Alongside the main trial there will be a parallel, trial-based cost-utility analysis (conducted by CIF Haines, an experienced health economist). This economic analysis will consider the incremental cost of each of the intervention conditions compared to the sham for gaining one quality adjusted life year. Quality adjusted life years will be calculated using an area under the curve approach on EQ-5D-5L utility scores collected at each assessment. These scores will be generated using the Dolan cross-walk approach. A societal perspective will be taken by calculating health care and productivity costs incurred by participants. Valuation of health services costs will be based on standard rates published by the Australian government (National Weighted Activity Unit costs for hospitalisations [The Independent Hospital Pricing Authority website. https://www.ihpa.gov.au/what-we-do/national-weighted-activity-unit-nwau-calculators-2015-16], Medical Benefits Schedule and Pharmaceutical Benefits Schedule prices for other subsidised health costs, market prices for other costs). Bootstrap resampling will be used to generate 95% confidence intervals for cost-utility estimates and for construction of acceptability curves. One-way sensitivity analyses will also be conducted to examine the impact of variation in key analysis inputs.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
18/11/2019
Actual
30/11/2019
Date of last participant enrolment
Anticipated
30/06/2022
Actual
11/07/2022
Date of last data collection
Anticipated
10/07/2023
Actual
7/07/2023
Sample size
Target
192
Accrual to date
Final
192
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment postcode(s) [1] 28195 0
3000 - Melbourne

Funding & Sponsors
Funding source category [1] 303969 0
Government body
Name [1] 303969 0
NHMRC
Country [1] 303969 0
Australia
Primary sponsor type
University
Name
Monash University
Address
Monash University
Wellington road, Clayton, VIC-3800
Country
Australia
Secondary sponsor category [1] 304140 0
None
Name [1] 304140 0
Address [1] 304140 0
Country [1] 304140 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 304469 0
Monash Human Research Ethics Committee
Ethics committee address [1] 304469 0
Monash University
Wellington road, Clayton, VIC-3800
Ethics committee country [1] 304469 0
Australia
Date submitted for ethics approval [1] 304469 0
12/12/2018
Approval date [1] 304469 0
05/08/2019
Ethics approval number [1] 304469 0
18138

Summary
Brief summary
The primary aim of the study is to examine the efficacy of TSI with steroid and TSI without steroid versus sham injection among individuals with Achilles tendinopathy at 12 months.
The primary outcome measure will be the Victorian Institute of Sport Assessment – Achilles (VISA-A) at 12 months.
Study hypothesis: TSI with steroid and TSI without steroid will lead to superior VISA-A outcome compared to sham at 12 months.
Trial website
https://www.monashachillesstudy.com/
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 97054 0
A/Prof Peter Malliaras
Address 97054 0
Department of Physiotherapy | School of Primary and Allied Health Care
Building B | Monash University | Peninsula Campus | Victoria, 3199 Australia
Country 97054 0
Australia
Phone 97054 0
+613 9904 4502
Fax 97054 0
Email 97054 0
[email protected]
Contact person for public queries
Name 97055 0
Peter Malliaras
Address 97055 0
Department of Physiotherapy | School of Primary and Allied Health Care
Building B | Monash University | Peninsula Campus | Victoria, 3199 Australia
Country 97055 0
Australia
Phone 97055 0
+613 9904 4502
Fax 97055 0
Email 97055 0
[email protected]
Contact person for scientific queries
Name 97056 0
Peter Malliaras
Address 97056 0
Department of Physiotherapy | School of Primary and Allied Health Care
Building B | Monash University | Peninsula Campus | Victoria, 3199 Australia
Country 97056 0
Australia
Phone 97056 0
+613 9904 4502
Fax 97056 0
Email 97056 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseEfficacy of high-volume injections with and without corticosteroid compared with sham for Achilles tendinopathy: a protocol for a randomised controlled trial.2021https://dx.doi.org/10.1136/bmjsem-2021-001136
N.B. These documents automatically identified may not have been verified by the study sponsor.