Clinical Trial Results:
Tendinopathy treatment effects and mechanisms 1 (TEAM 1): A randomised clinical trial of eccentric loading, high volume injection and shock wave therapy for Achilles tendinopathy.
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Summary
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EudraCT number |
2015-000196-27 |
Trial protocol |
GB |
Global end of trial date |
31 Dec 2020
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Results information
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Results version number |
v1(current) |
This version publication date |
11 Jan 2022
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First version publication date |
11 Jan 2022
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
9744
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Additional study identifiers
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ISRCTN number |
ISRCTN75305839 | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
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Sponsors
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Sponsor organisation name |
QMUL - JRMO
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Sponsor organisation address |
5 Walden Street, London, United Kingdom, E1 2EF
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Public contact |
Burtles, QMUL, +44 02078827260, sponsorsrep@bartshealth.nhs.uk
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Scientific contact |
Burtles, QMUL, +44 02078827260, sponsorsrep@bartshealth.nhs.uk
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Interim
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Date of interim/final analysis |
22 Nov 2021
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
31 Dec 2020
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Global end of trial reached? |
Yes
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Global end of trial date |
31 Dec 2020
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The overarching aim is to test the effectiveness and cost effectiveness of Radial Shock Wave Therapy (RSWT) and High Volume Image Guided Injection (HVIGI) when added to usual practice (progressive eccentric loading - EL).
The primary aim will be realised by a three-centre, three-armed randomised clinical trial of EL (usual treatment) compared to EL plus RSWT and HVIGI plus EL. The primary outcome measure will be the Victorian Institute of Sport Assessment – Achilles (VISA-A), a well validated and reliable measure of function and recent pain at twelve months. Subjects will be stratified by activity level.
To identify a clinically meaningful difference between groups of 15 on the VISA-A at a power of 90% and a significance level of 2.5% (Bonferroni correction for multiple comparisons) at the twelve month post treatment follow-up we will recruit 180 participants. Subsequent follow-ups at one and two years will assess long-term treatment effects.
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Protection of trial subjects |
Participants had access to trial team contact numbers and email addresses should the need any assistance. Participants were provided with information leaflets and exercise diaries indicating acceptable levels of pain following interventions. Policies and procedures were in place in respect to injections provided within radiology departments.
Radial shock wave therapy (RSWT) is approved for treating Achilles tendinopathy by NICE provided audit is undertaken of effects, and side effects, for every patient. The trial will effectively do this to a greater extent than our current clinical service. Further, our follow-up will be more extensive than the current ASSERT protocol, which the lead researcher helped design.
High volume image guided injection (HVIGI) has not been subject to rigorous evaluation as yet. Two trials have completed but these have not fully reported (in Leeds NCT01583504, and Denmark). It has been subject to 5 published case series with no reports of significant negative effects, and is routine clinical care at the participating sites. The technique was developed at the London Hospital and related sites, and the first reports were delivered by the lead researcher. The MHRA algorithm shows this is a CTIMP, and initial advice from the MHRA is that this trial is a type A CTIMP, as the injectates are being used for a common application. Hydrocortisone acetate or aprotinin have additionally been used in some studies. We will not use these as there are theoretical risks associated and we have emerging evidence from two trials of no difference in effect.
Barts Health NHS trust / QMUL policies and procedures were followed for all untoward events
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Background therapy |
Achilles tendinopathy (AT) is common, recurrent, painful and limits the activity of those affected. It causes substantial direct NHS costs and substantial indirect costs due to reduced physical activity participation. There are consequential effects on occupation and exercise for health. Taken collectively, tendinopathies are the second most common problem seen by physiotherapists in the NHS. Tendinopathies are typically slow to respond to conservative treatment, usually consisting of progressive eccentric loading (EL), a form of muscle contraction while lengthening with good evidence. No established interventions have high success rates. We do not know why some people improve and others do not. Surgery often has unsatisfactory outcomes, many side effects and long recovery periods. The first line of management is usually conservative. An exercise programme that emphasises eccentric loading (EL) is a specific exercise regime where the triceps surae is loaded as it lengthens – rather than statically or as it shortens. We recently demonstrated that there is strong evidence for application of a three-month EL programme and for shock wave therapy.(1) Further, we found that physiotherapists are typically aware of, and apply, the evidence for this protocol which is now established as best usual care. These interventions typically result in only 60-80% of participants returning to full activity. | ||
Evidence for comparator |
Recent advances have suggested that two intermediate interventions – shock wave therapy (SWT) and high volume image guided injection (HVIGI) – have the potential to improve outcomes for people with tendinopathy. SWT typically involves three treatments, one week apart, and is increasingly accepted into mainstream practise with stage ll clinical trials demonstrating some efficacy. HVIGI has only been subject to evaluation by case series with some encouraging findings of statistically significant and clinically meaningful improvements on well-validated outcome measures. SWT: Rompe JD, Furia J, Maffulli N. Eccentric loading versus eccentric loading plus shock-wave treatment for midportion achilles tendinopathy: a randomized controlled trial. The American journal of sports medicine. 2009;37(3):463-70. HVIGI: Chan O, O'Dowd D, Padhiar N, Morrissey D, King J, Jalan R, et al. High volume image guided injections in chronic Achilles tendinopathy. Disability and rehabilitation. 2008;30(20-22):1697-708. Crisp T, Khan F, Padhiar N, Morrissey D, King J, Jalan R, et al. High volume ultrasound guided injections at the interface between the patellar tendon and Hoffa's body are effective in chronic patellar tendinopathy: A pilot study. Disability and rehabilitation. 2008;30(20-22):1625-34. Humphrey J, Chan O, Crisp T, Padhiar N, Morrissey D, Twycross-Lewis R, et al. The short-term effects of high volume image guided injections in resistant noninsertional Achilles tendinopathy. Journal of science and medicine in sport / Sports Medicine Australia. 2010;13(3):295-8. Morton S, Chan O, King J, Perry D, Crisp T, Maffulli N, et al. High volume image-guided Injections for patellar tendinopathy: a combined retrospective and prospective case series. Muscles, ligaments and tendons journal. 2014;4(2):214-9. Coombes BK, Bisset L, Vicenzino B. Efficacy and safety of corticosteroid injections and other injections for management of tendinopathy: | ||
Actual start date of recruitment |
01 Jun 2015
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
United Kingdom: 185
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Worldwide total number of subjects |
185
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EEA total number of subjects |
0
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
185
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
Date trial opened to recruitment: 17/12/2015 Date first randomisation: 07/01/2016 Date of last randomisation: 21/12/2018 Target Recruitment: 180 Trial Status: Completed Number recruited: 185 Number of sites that have recruited: 3 Bartshealth: 171 Homerton University Hospital: 12 Royal Free Hospital: 2 | ||||||||||||||||||||||||||||||||||||||||||||
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Pre-assignment
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Screening details |
Screened for eligibility (n=524), Excluded (n=339) • Pre-screen failures - Not meeting inclusion criteria (n=85) • Screened failures – Not meeting inclusion criteria (n=126) • Declined to participate (n=72) • No contact (n=56) Randomised (185) | ||||||||||||||||||||||||||||||||||||||||||||
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Period 1
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Period 1 title |
Baseline to 12 months (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Not blinded | ||||||||||||||||||||||||||||||||||||||||||||
Blinding implementation details |
Independent assessor was blinded to trial arm during final 12 month assessment.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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EL - Progressive Eccentric Loading | ||||||||||||||||||||||||||||||||||||||||||||
Arm description |
All patients receive a progressive loading intervention with eccentric loading as a key element. A pain monitoring model is used to determine progression of rehabilitation, and patients enter the rehabilitation at the level of difficulty determined by their pain. | ||||||||||||||||||||||||||||||||||||||||||||
Arm type |
Active comparator | ||||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Exercise - Eccentric Progressive Loading
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Investigational medicinal product code |
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Other name |
Exercise Therapy, Loading, Eccentrics, Progressive Loading
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Pharmaceutical forms |
Not assigned
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Routes of administration |
External use
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Dosage and administration details |
Progressive Loading - 8 supervised exercises sessions over 12 weeks with addition of home exercise programme.
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Arm title
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EL+SWT | ||||||||||||||||||||||||||||||||||||||||||||
Arm description |
SWT treatment to be administered with settings at 10 Hz with intensity starting at 2.2 bar and increasing, dependent upon patient tolerance levels (pain monitoring model). The treatment duration is 4 minutes, and patients will be provided post-treatment advice as per clinical routine management. | ||||||||||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Extracorporeal Shockwave Therapy
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Investigational medicinal product code |
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Other name |
Shockwave
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Pharmaceutical forms |
Not assigned
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Routes of administration |
Extracorporeal use
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Dosage and administration details |
Key points from SOP: V4.0 TEAM 1 Shockwave Administering SOP 10022020
1.Administering clinician to confirm consent as per departmental guidelines prior to treatment. *Note participant has already consented to treatment prior to randomisation for trial purposes*
2. Explain rationale behind treatment to patient as appropriate.
3. Clinician to ensure the shockwave machine is plugged in and suitable for use. Check the water bottle is empty.
4. Device switched on, first treatment settings 10.0Hz, 2500 pulses, R15 silver probe, Ramp ON and starting from 2.8 Bar
7. Patient to be informed that treatment may be uncomfortable (up to 5/10 on the pain monitoring model is fine) advised to liaise with clinician
11. If well tolerated at 2.8 Bar then dose can be increased incrementally as per pain monitoring model.
13. Patient to be informed that three consecutive weekly appointments required. A one week gap is not ideal but is permissible.
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Arm title
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EL+HVIGI | ||||||||||||||||||||||||||||||||||||||||||||
Arm description |
Patients are injected with 40 mL of injectable normal saline, mixed with 10 mL of 0.5 % bupivacaine hydrochloride. This is typically administered once, via ultrasound-guided injection to the area immediately adjacent to the primary. | ||||||||||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
High Volume Image Guided Injection
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Investigational medicinal product code |
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Other name |
HVIGI
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Pharmaceutical forms |
Injection
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Routes of administration |
Injection
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Dosage and administration details |
The preparation and administration of the injection requires the following steps:
• Under sterile conditions and using a giving set;
• Using a 10ml syringe with (for example) a male luer lock fitting and a (for example) a green 21 gauge 40mm needle the local anaesthetic is drawn up;
• Four further 10ml syringes have 10ml each of normal saline drawn up and set aside;
• The local anaesthetic is then attached to a tube with (for example) a female luer lock with a (for example) green 21 gauge 40mm needle also attached;
• The needle is inserted between, but not into, the Achilles and the Kager’s fat pad under ultrasound guidance to ensure needle positioning deep to the main site of maximum pathology, without insertion into the tendon itself;
• The first 10ml syringe is then administered, followed by up to four syringes (as tolerated by patient) of normal saline. If the patient cannot tolerate the full 50mls then this is not classified as a protocol deviation.
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| Notes [1] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left. Justification: Numbers entered at 'started' are the total numbers recruited, subsequent milestone numbers are for those who completed the follow-ups minus those who withdrew or were lost to follow-up. The 'completed' number accounts for all the participants who attended and completed the final 12 month review minus those who withdrew or were lost to follow-up. [2] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left. Justification: Numbers entered at 'started' are the total numbers recruited, subsequent milestone numbers are for those who completed the follow-ups minus those who withdrew or were lost to follow-up. The 'completed' number accounts for all the participants who attended and completed the final 12 month review minus those who withdrew or were lost to follow-up. [3] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left. Justification: Numbers entered at 'started' are the total numbers recruited, subsequent milestone numbers are for those who completed the follow-ups minus those who withdrew or were lost to follow-up. The 'completed' number accounts for all the participants who attended and completed the final 12 month review minus those who withdrew or were lost to follow-up. [4] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left. Justification: Numbers entered at 'started' are the total numbers recruited, subsequent milestone numbers are for those who completed the follow-ups minus those who withdrew or were lost to follow-up. The 'completed' number accounts for all the participants who attended and completed the final 12 month review minus those who withdrew or were lost to follow-up. [5] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left. Justification: Numbers entered at 'started' are the total numbers recruited, subsequent milestone numbers are for those who completed the follow-ups minus those who withdrew or were lost to follow-up. The 'completed' number accounts for all the participants who attended and completed the final 12 month review minus those who withdrew or were lost to follow-up. [6] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left. Justification: Numbers entered at 'started' are the total numbers recruited, subsequent milestone numbers are for those who completed the follow-ups minus those who withdrew or were lost to follow-up. The 'completed' number accounts for all the participants who attended and completed the final 12 month review minus those who withdrew or were lost to follow-up. [7] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left. Justification: Numbers entered at 'started' are the total numbers recruited, subsequent milestone numbers are for those who completed the follow-ups minus those who withdrew or were lost to follow-up. The 'completed' number accounts for all the participants who attended and completed the final 12 month review minus those who withdrew or were lost to follow-up. [8] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left. Justification: Numbers entered at 'started' are the total numbers recruited, subsequent milestone numbers are for those who completed the follow-ups minus those who withdrew or were lost to follow-up. The 'completed' number accounts for all the participants who attended and completed the final 12 month review minus those who withdrew or were lost to follow-up. [9] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left. Justification: Numbers entered at 'started' are the total numbers recruited, subsequent milestone numbers are for those who completed the follow-ups minus those who withdrew or were lost to follow-up. The 'completed' number accounts for all the participants who attended and completed the final 12 month review minus those who withdrew or were lost to follow-up. |
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Baseline characteristics reporting groups
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Reporting group title |
EL - Progressive Eccentric Loading
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Reporting group description |
All patients receive a progressive loading intervention with eccentric loading as a key element. A pain monitoring model is used to determine progression of rehabilitation, and patients enter the rehabilitation at the level of difficulty determined by their pain. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
EL+SWT
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Reporting group description |
SWT treatment to be administered with settings at 10 Hz with intensity starting at 2.2 bar and increasing, dependent upon patient tolerance levels (pain monitoring model). The treatment duration is 4 minutes, and patients will be provided post-treatment advice as per clinical routine management. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
EL+HVIGI
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Reporting group description |
Patients are injected with 40 mL of injectable normal saline, mixed with 10 mL of 0.5 % bupivacaine hydrochloride. This is typically administered once, via ultrasound-guided injection to the area immediately adjacent to the primary. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
VISA-A Outcome Measure
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Subject analysis set type |
Intention-to-treat | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
The primary outcome will be VISA-A score and we will test the hypothesis that there is no difference in this between the EL+HVIGI and EL alone arms over the study period using a multilevel model with random effects to account for clustering (recruitment centre) and repeated measures, and adjustment for activity level and VISA-A score at entry to the study. A similar model will be fitted to test the hypothesis that there is no difference in VISA-A score between the EL alone and EL_ESWI treatment arms. Multilevel models will also be used to investigate the effect of patient characteristics on outcomes. Where appropriate, a similar approach will be applied to the analysis of secondary outcomes. All analyses will be on an intention to treat basis.
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End points reporting groups
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Reporting group title |
EL - Progressive Eccentric Loading
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Reporting group description |
All patients receive a progressive loading intervention with eccentric loading as a key element. A pain monitoring model is used to determine progression of rehabilitation, and patients enter the rehabilitation at the level of difficulty determined by their pain. | ||
Reporting group title |
EL+SWT
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Reporting group description |
SWT treatment to be administered with settings at 10 Hz with intensity starting at 2.2 bar and increasing, dependent upon patient tolerance levels (pain monitoring model). The treatment duration is 4 minutes, and patients will be provided post-treatment advice as per clinical routine management. | ||
Reporting group title |
EL+HVIGI
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Reporting group description |
Patients are injected with 40 mL of injectable normal saline, mixed with 10 mL of 0.5 % bupivacaine hydrochloride. This is typically administered once, via ultrasound-guided injection to the area immediately adjacent to the primary. | ||
Subject analysis set title |
VISA-A Outcome Measure
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Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
The primary outcome will be VISA-A score and we will test the hypothesis that there is no difference in this between the EL+HVIGI and EL alone arms over the study period using a multilevel model with random effects to account for clustering (recruitment centre) and repeated measures, and adjustment for activity level and VISA-A score at entry to the study. A similar model will be fitted to test the hypothesis that there is no difference in VISA-A score between the EL alone and EL_ESWI treatment arms. Multilevel models will also be used to investigate the effect of patient characteristics on outcomes. Where appropriate, a similar approach will be applied to the analysis of secondary outcomes. All analyses will be on an intention to treat basis.
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End point title |
VISA-A | ||||||||||||||||||||
End point description |
The primary outcome will be VISA-A score and we will test the hypothesis that there is no difference in this between the EL+HVIGI and EL alone arms over the study period using a multilevel model with random effects to account for clustering (recruitment centre) and repeated measures, and adjustment for activity level and VISA-A score at entry to the study. A similar model will be fitted to test the hypothesis that there is no difference in VISA-A score between the EL alone and EL_ESWI treatment arms. Multilevel models will also be used to investigate the effect of patient characteristics on outcomes. Where appropriate, a similar approach will be applied to the analysis of secondary outcomes. All analyses will be on an intention to treat basis.
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End point type |
Primary
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End point timeframe |
12 months from date of intervention starting.
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Statistical analysis title |
VISA-A Analysis | ||||||||||||||||||||
Statistical analysis description |
The primary outcome will be VISA-A score and we will test the hypothesis that there is no difference in this between the EL+HVIGI, EL+SWT and EL alone arms over the study period using a multilevel model with random effects to account for clustering (recruitment centre) and repeated measures, and adjustment for activity level and VISA-A score at entry to the study.
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Comparison groups |
EL+SWT v EL+HVIGI v EL - Progressive Eccentric Loading
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Number of subjects included in analysis |
168
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||||||||||
P-value |
≤ 0.05 | ||||||||||||||||||||
Method |
Mixed models analysis | ||||||||||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||||||||||
Confidence interval |
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level |
95% | ||||||||||||||||||||
sides |
2-sided
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lower limit |
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upper limit |
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Variability estimate |
Standard deviation
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Adverse events information
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Timeframe for reporting adverse events |
All Serious Adverse Events (SAEs) will be recorded in the subjects’ notes, the CRF, the sponsor SAE form and reported to the Joint Research and Development Office (JRMO) within 24 hours of the site becoming aware of the event.
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Adverse event reporting additional description |
If the AE is not defined as SERIOUS, the AE is recorded in the trial file and the participant is followed up by the research team. The AE is documented in the participants’ medical notes (where appropriate) and the CRF.
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Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
JRMO | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
1
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Reporting groups
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Reporting group title |
TEAM-1 - Eccentric Loading
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Reporting group description |
All patients receive a progressive loading intervention with eccentric loading as a key element. A pain monitoring model is used to determine progression of rehabilitation, and patients enter the rehabilitation at the level of difficulty determined by their pain. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
TEAM-1 - ESWT
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Reporting group description |
SWT treatment to be administered with settings at 10 Hz with intensity starting at 2.2 bar and increasing, dependent upon patient tolerance levels (pain monitoring model). The treatment duration is 4 minutes, and patients will be provided post-treatment advice as per clinical routine management. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
TEAM-1 HVIGI
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Reporting group description |
Patients are injected with 40 mL of injectable normal saline, mixed with 10 mL of 0.5 % bupivacaine hydrochloride. This is typically administered once, via ultrasound-guided injection to the area immediately adjacent to the primary. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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16 Dec 2016 |
substantial amendment to our study, so we can open new sites. These include:
minor changes and clarifications to the PIS, ICF and protocol.
o the inclusion and exclusion criteria have been simplified and one test removed; o typographical errors amended.
A change of PI at the Homerton University Hospital NHS Trust |
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04 Dec 2017 |
Substantial amendment 2 includes the following changes:
· Addition of a new site with associated new PI, Mr Haroon Mann
o Royal Free Hospital
· Protocol:
o Correction of an error about the ultrasound confirmation on the previous version. A formatting error meant the ultrasound confirmation moved from being in the inclusion criteria in the submitted version to exclusion criteria section. No patients have had their care or trial status affected as a result. This has been discussed with the sponsor, with the decision being to deal with this in the current amendment.
o Minor clarifications to inclusion / exclusion criteria, in order to remove duplications and prevent unnecessary exclusions for irrelevant auto-immune and connective tissue diseases
o Changes to site numbers and names, as outlined in the attached NoSA form
o Other minor grammatical and formatting changes
o Clarification of foreseeable Adverse events
o Clarification of the allowed window for assessments
o Clarification of the IMP administration
· Notification of exercise diary template
o Our exercise diary template is included as it was omitted from the previous REC application, as highlighted by an audit
· An amended topic guide for the process evaluation interviews is included
o This is to more closely match the information we think is important to extract from the process evaluation.
· Poster
· Two images with associated text are submitted to be used on social media
· An amended post injection leaflet is attached, v2.0
· Notification of costs questionnaires
Extension of recruitment time to allow target and follow-ups to be reached
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01 May 2020 |
Substantial Amendment 3:
The amendment includes the following changes:
· Addition of a new statistician Rachael Adcock
· Notification of intention to commence data analysis on completion of final participant’s 12-month review (primary end-point) instead of 24 month review.
· Protocol:
o Minor clarification detailing the above change to data analysis plan
o Minor clarification of change in 24-month review to remote assessment as per non-substantial amendment (31/03/2020) |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
