E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Musculoskeletal Diseases [C05] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10050471 |
E.1.2 | Term | Achilles tendon pain |
E.1.2 | System Organ Class | 100000004859 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | 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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E.2.2 | Secondary objectives of the trial |
Secondary measures will include: recent pain (VAS score); treatment satisfaction (Likert scale); adherence (exercise diaries); adverse events (overtly solicited self report); global perceived change (Likert scale); ankle and foot function (FAOS); self-reported exercise levels (modified IPAQ); health-related quality of life (EQ-5D); calf function (using a clinical graded loading challenge). Further, we will collect data on costs and interview participants and care delivery staff concerning trial delivery. All measures will be applied at baseline and 6 weeks, then 3, 6, 12 and 24 months post-randomisation.
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E.2.3 | Trial contains a sub-study | No |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
We will be adding a mechanistic parallel study, subject to funding, at a later date. This will be subject to a separate ethics application. |
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E.3 | Principal inclusion criteria |
Patients will be included if they are aged between 18 and 64 with a greater than three month history of pain in the mid-Achilles area. Clinical diagnosis will be established by • gradual onset of pain in the relevant area • pain that worsens during and soon after exercise • confirmation by palpation of the mid-tendon • positive London Hospital test (King, 2000) • ankle joint examination • The squeeze and Simmonds tests must be negative to exclude rupture. • an absence of a frank tear history. • Ultrasound confirmation of clinical findings
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E.4 | Principal exclusion criteria |
Exclusion criteria include o having had a steroid injection to the area in the last 1 year o history of known fluorquinolone antibiotic use in the last two years o Concurrent Participation on another Clinical Trial of an Investigational Medicinal Product • Participation in other trials for Achilles tendon or musculoskeletal lower limb pathology o having had SWT to Achilles in the last 1 year • Allergies to any of the potential injectates o a history of a previous Achilles tear o have pain predominantly at the tendon insertion to exclude those with insertional tendinopathy o known to have an inherited disorder of connective tissue disease or autoimmune diseases of connective tissue Known chronic kidney disease at grade 4 (Known CDK4) • unable to provide informed consent • current or suspected pregnancy or breastfeeding • or have any further medical and/or social reason that would preclude involvement as determined by an Investigator. • Participation in a clinical trial of an investigational medicinal product in the last 90 days. • A serious mental health problems that would preclude adherence to study or treatment protocols • Known hypersensitivity to study drugs • Local infection or active systematic infection that would be a contra-indication to use of glucocorticoid drugs (e.g. chickenpox or measles) • Known immune deficiency |
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E.5 End points |
E.5.1 | Primary end point(s) |
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. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
12 months after trial entry. |
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E.5.2 | Secondary end point(s) |
A range of secondary outcomes have been selected for three purposes. 1: to explore the trial results. 2: to evaluate cost-effectiveness 3: a process evaluation to understand factors explaining the success or otherwise of the interventions.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
exercise or shock wave therapy |
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E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 3 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 9 |
E.8.9.2 | In all countries concerned by the trial days | 31 |