Plaster cast versus functional bracing for Achilles tendon rupture: the UKSTAR RCT

Article history

The research reported in this issue of the journal was funded by the HTA programme as project number 13/115/62. The contractual start date was in April 2016. The draft report began editorial review in June 2019 and was accepted for publication in October 2019. The authors have been wholly responsible for all data collection, analysis and interpretation, and for writing up their work. The HTA editors and publisher have tried to ensure the accuracy of the authors’ report and would like to thank the reviewers for their constructive comments on the draft document. However, they do not accept liability for damages or losses arising from material published in this report.

Declared competing interests of authors

Matthew L Costa is a National Institute for Health Research (NIHR) Senior Investigator and a member of the NIHR Health Technology Assessment (HTA) General Board (1 November 2016 to present). Rebecca S Kearney is a member of the NIHR HTA Clinical Evaluation and Trials Board (8 November 2018–present) and the NIHR Integrated Clinical Academic Doctoral Panel (29 November 2017–present) and was a member of NIHR Research for Patient Benefit Board (28 January 2016–24 January 2019). Sarah E Lamb reports that she was a member of the following boards: HTA Additional Capacity Funding Board (2012–15); HTA Clinical Trials Board (2010–15); HTA End of Life Care and Add on Studies (2015); HTA Funding Boards Policy Group (formerly Clinical Specialty Group) (2010–15); HTA Maternal, Neonatal, Child Health Methods Group (2013–15); HTA Post-board funding teleconference (2010–15); HTA Primary Care Themed Call Board (2013–14); HTA Prioritisation Group (2012–15); and the NIHR Clinical Trials Unit Standing Advisory Committee (2012–16). Stavros Petrou is a NIHR Senior Investigator.

Copyright statement

© Queen’s Printer and Controller of HMSO 2020. This work was produced by Costa et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK.

2020 Queen’s Printer and Controller of HMSO

Background

The Achilles tendon is the largest tendon in the human body and transmits the powerful contractions of the calf muscles that are required for walking and running. A rupture of this tendon is painful and has an immediate and serious detrimental impact on daily activities of living. 1 In the longer term, tendon rupture results in prolonged periods off work and time away from sporting activity (average time away from work is between 4 and 8 weeks and time away from sport is between 26 and 39 weeks). 1 This results in lost income and restricted daily activities in the early phase and reduced physical activity, with associated negative health and social consequences, in the long term. For high-level sportsmen it is frequently a ‘career-ending’ injury.

Achilles tendon rupture affects > 11,000 people each year in the UK, and the incidence is increasing as the population remains more active into older age. 2 It affects all age groups in a bimodal distribution, with the first peak in patients aged 30–40 years and the second in patients aged 60–80 years. 2 The first peak in incidence is often associated with participation in sport, such as football and racquet sports, whereas the second peak often occurs during normal daily activities, such as climbing stairs. 2,3 However, all Achilles tendon ruptures are associated with a pre-existing ‘tendinopathy’, which is attributed to failures in the protective/regenerative functions that respond to repeated microscopic injury. 4,5

Historically, the main question in relation to the management of patients with rupture of the Achilles tendon has been whether or not to perform a surgical repair of the tendon. In 1981, Nistor6 designed and published the first randomised controlled trial (RCT) to address this clinical question. This study was followed by a series of RCTs that were pooled in a meta-analysis by the Cochrane review group in 2004. 7 The results suggested that surgical repair reduced the risk of re-rupture, but this came with an increased cost and a greatly increased risk of other complications, most of which were associated with infection and wound healing. There were few data on functional outcome at the time of this review. More recent trials comparing surgical repair and non-operative treatment have found no difference in functional outcome. 8,9 As surgery carries considerable costs, and carries considerable risks to the patient in terms of complications,7 there is an increasing trend towards non-operative treatment. However, some surgeons have been reluctant to advocate non-operative treatment because of concerns about the lack of evidence to guide early rehabilitation for this group of patients,10 specifically whether or not functional bracing is safe and effective if the tendon has not been not surgically repaired.

Traditionally, patients have been treated in plaster casts after rupture of the Achilles tendon, with the cast immobilising the foot and ankle while the tendon heals. 11 However, there are potential problems with this approach. First, there is the immediate impact on mobility for a period of around 8 weeks, affecting activities of daily life. Second, there are the complications and risks associated with prolonged immobilisation: muscle atrophy, deep-vein thrombosis (DVT) and joint stiffness. 12,13 Finally, there are the potential long-term consequences, which include prolonged gait abnormalities, persistent calf muscle weakness and an inability to return to previous activity levels. 14 Functional bracing, involving immediate, protected weight-bearing in a brace, was designed to address these issues.

In patients having a surgical repair, seven RCTs,1,15–20 directly comparing plaster casts with early movement and/or weight-bearing in a ‘functional brace’, had been conducted at the time that the protocol was developed for the UK Study of Tendo Achilles Rehabilitation (UKSTAR). The results favoured functional bracing in terms of re-rupture rate, functional outcome and quality-of-life (QoL) measures. Therefore, in the first guideline produced on this topic in 2009,21 the American Academy of Orthopaedic Surgeons recommended functional bracing for patients undergoing surgical repair of their tendon.

Pre-pilot data

Before UKSTAR, we completed four phases of pilot and preparatory work to establish the following.

Research objectives

The primary objective was to quantify and draw inferences about observed differences in ATRS between the trial treatment groups at 9 months post injury.

The secondary objectives were to:

• quantify and draw inferences about observed differences in ATRS between the trial treatment groups at 8 weeks and 3 and 6 months post injury

• identify any differences in HRQoL between the trial treatment groups in the first 9 months post injury

• determine the complication rate of the trial treatment groups in the first 9 months post injury

• investigate, using appropriate statistical and economic analytical methods, the resource use, costs and comparative cost-effectiveness of the trial treatment groups in the first 9 months post injury.

Patient and public involvement

We have been working with and listening to the views of patients with Achilles tendon injuries for many years. However, as well as this informal contribution, a series of formal qualitative interviews with patients and clinicians were carried out in the development of the UKSTAR (ISRCTN68273773). 11 The views of patients were used to inform and refine the trial interventions and processes, in particular the development of the trial information and materials. The patient perspective was key during the development of the trail protocol to ensure that the interventions, and participation in the trial, would be acceptable.

Two of the patients who contributed to our development work agreed to act as lay representatives on the Trial Management Group (TMG) and as co-applicants on the research grant award. Mrs Richmond later had to leave the research team for personal reasons, but Mr Grant attended TMG meetings throughout the trial and contributed to all trial process and paperwork, with particular input on patient information leaflets. Mr Grant will be crucially involved in the dissemination of the study findings to the wider public. He will lead the development of any materials, leaflets and website information to be used for this purpose. Mr Grant has reviewed the Plain English summary of this report.

Mr Grant was supported by the chief investigator and the trial co-ordination team. He had peer support from the UK musculoskeletal trauma patient and public involvement (PPI) group, hosted in Oxford. He also had access to and support from the University/User Teaching and Research Action Partnership network through University of Warwick, an organisation that promotes the engagement and involvement of service users and carers from the local community in research and teaching in health and social care.

Summary of study design

UKSTAR was a multicentre, randomised, pragmatic, two-group superiority trial. Patients presenting at 39 NHS hospitals in England and Scotland with an acute primary Achilles tendon rupture for non-surgical treatment were randomised 1 : 1 to receive either functional brace or plaster cast.

Settings and locations

The 39 NHS hospital orthopaedic or trauma clinics in England and Scotland that screened and recruited participants for this trial were:

1. King’s College Hospital NHS Foundation Trust

2. Nottingham University Hospitals NHS Trust

3. Royal Berkshire Hospital, Royal Berkshire NHS Foundation Trust

4. Aberdeen Royal Infirmary, NHS Grampian

5. Ninewells Hospital and Medical School, NHS Tayside

6. Glasgow Royal Infirmary, NHS Greater Glasgow and Clyde

7. Pilgrim Hospital, United Lincolnshire Hospitals NHS Trust

8. University Hospital of North Tees, North Tees and Hartlepool Hospitals NHS Foundation Trust

9. Airedale NHS Foundation Trust

10. Salisbury District Hospital, Salisbury NHS Foundation Trust

11. The Rotherham NHS Foundation Trust

12. George Eliot Hospital NHS Trust

13. James Paget University Hospitals NHS Foundation Trust, Great Yarmouth

14. Southampton General Hospital, University Hospital Southampton NHS Foundation Trust

15. Lister Hospital, East and North Hertfordshire NHS Trust

16. Royal Cornwall Hospital, Royal Cornwall Hospitals NHS Trust

17. Tunbridge Wells Hospital, Maidstone and Tunbridge Wells NHS Trust

18. Addenbrooke’s Hospital, Cambridge University Hospitals NHS Foundation Trust

19. Derriford Hospital, University Hospitals Plymouth NHS Trust

20. Hull Royal Infirmary, Hull University Teaching Hospitals NHS Trust

21. Luton and Dunstable University Hospital NHS Foundation Trust

22. Salford Royal NHS Foundation Trust

23. Scunthorpe General Hospital, Northern Lincolnshire and Goole NHS Foundation Trust

24. Pinderfields Hospital, The Mid Yorkshire Hospitals NHS Trust

25. Leeds General Infirmary, Leeds Teaching Hospitals NHS Trust

26. Worcestershire Royal Hospital, Worcestershire Acute Hospitals NHS Trust

27. Doncaster Royal Infirmary, Doncaster and Bassetlaw Teaching Hospitals NHS Foundation Trust

28. St Helier Hospital, Epsom and St Helier University Hospitals NHS Trust

29. St Mary’s Hospital, Imperial College Healthcare NHS Trust

30. Raigmore Hospital, NHS Highland

31. Whiston Hospital, St Helens and Knowsley Hospitals NHS Trust

32. Milton Keynes University Hospital NHS Foundation Trust

33. Warwick Hospital, South Warwickshire NHS Foundation Trust

34. Queen’s Hospital, Burton Hospitals NHS Foundation Trust

35. Hereford County Hospital, Wye Valley NHS Trust

36. Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust

37. John Radcliffe Hospital, Oxford University Hospitals NHS Foundation Trust

38. University Hospital of South Manchester NHS Foundation Trust

39. Musgrove Park Hospital, Taunton and Somerset NHS Foundation Trust.

Participants

Baseline assessment

Potential participants were allowed as much time as they needed to consider the trial information and had the opportunity to ask questions of the attending clinical team and a member of the research team. The trial information was delivered verbally and in writing, detailing the exact nature of the study, the implications and constraints of the protocol, what to expect as a participant and any risks involved in taking part. It was stated clearly that the participant was free to withdraw from the study at any time, for any reason, without prejudice to future care and with no obligation to give the reason for withdrawal. If the patient was happy to participate, they were asked to sign and date a consent form, which was also signed and dated by the person who obtained consent. Consent was obtained by an appropriately trained member of the research team who had been delegated to do so by the local principal investigator.

A copy of the signed consent form was given to the participant and another copy was sent to the study co-ordinating team in Oxford to facilitate central monitoring. The original signed consent form was retained in the medical notes and a copy was held in the investigator site file. Consent forms were held in a secure location separately from study data. Permission was obtained to inform the participant’s general practitioner (GP) about study participation.

Participants were asked for their consent for their name and contact details (including address, telephone numbers and e-mail address) to be collected to facilitate follow-up, data collection and reporting of results, and for a copy of their contact details to be sent to the UKSTAR central office team in Oxford. The study team used these details to contact participants for follow-up at the 3-, 6- and 9-month time points, to resolve queries and to send a thank-you letter when a participant’s involvement in the trial ended.

Permission was sought to allow members of the University of Oxford or the NHS trust who were responsible for monitoring or audit of the study to access participant data, to ensure compliance with regulations.

Following consent, baseline data were collected and the participant was randomised. The treatment took place at the same visit. A Good Clinical Practice-trained member of the local research team oversaw the participant’s completion of the paper baseline questionnaire, which included:

• date, mechanism and side of injury

• baseline demographics – height, weight, smoking and alcohol status, employment status

• current medication

• medical history – diabetes mellitus, rheumatoid arthritis, lower limb fracture, ligament, tendon or nerve injury to lower limb in last 12 months, arthritis, Achilles tendinopathy or other relevant conditions.

Randomisation

Participants were randomly allocated (1 : 1) to either functional bracing or plaster cast using a computer-generated allocation sequence, stratified by recruitment centre, via a secure, centralised web-based randomisation service provided by the Oxford Clinical Trials Research Unit (OCTRU). The research associate informed the treating clinical team of the allocated treatment.

Stratification by recruitment centre helped to ensure that any cluster effect related to the recruitment centre itself was equally distributed between the trial groups. The catchment area was similar for all of the recruitment centres (each recruitment centre was a trauma unit dealing with these injuries on a daily basis). All of the recruitment centres were familiar with both techniques (i.e. the clinical staff used both plaster casts and functional bracing as part of their routine clinical practice).

Post-randomisation withdrawals

Participants were free to decline to take part in, consent to take part in or withdraw from the trial at any time without prejudice and without affecting the standard of care that they received. Participants had two options for withdrawal:

1. to withdraw from completing further questionnaires, but allow the trial team to view and record de-identified data are recorded as part of the normal standard of care

2. to withdraw wholly from the study and permit data obtained only up to the point of withdrawal to be included in the final analysis.

Withdrawn participants were not replaced, as the target sample size allowed for losses to follow-up.

Interventions

Participants received their allocated treatment (plaster cast or functional brace) following randomisation.

Although the principles of application of both plaster casts and functional brace are inherent in the technique, there are different types of plaster cast material and functional brace design. Each patient underwent the allocated intervention as specified below (see Table 9), but the details of application and materials used for the plaster and brace were left to the discretion of the treating clinician, as per their usual practice. This was intended to ensure that the results could be generalised across the NHS.

Rehabilitation

At the patient’s 8-week clinic appointment, the plaster cast or functional brace was removed unless the clinical team directed otherwise. All participants were provided with the same standardised written physiotherapy advice, detailing the exercises that they needed to perform for rehabilitation. This advice was based on a published systematic review of current rehabilitation protocols. 30 All of the participants were advised to move their toes, ankle and knee joints fully, within the limits of their comfort, and walking was encouraged. In this pragmatic trial, any other rehabilitation input beyond the written physiotherapy advice (including a formal referral to physiotherapy) was left to the discretion of the treating clinician. A record of any rehabilitation input (type and number of additional appointments), as well as other investigations or interventions, was collected as part of the 8-week and 3-, 6- and 9-month follow-up questionnaires.

Outcome measures

Adverse events

An adverse event (AE) is defined as any untoward medical occurrence in a clinical trial subject and does not necessarily have a causal relationship with the treatment. All AEs were listed on the CRF for routine return to the UKSTAR central office.

A serious adverse event (SAE) is defined as any untoward and unexpected medical occurrence that:

• results in death

• is life-threatening

• requires hospitalisation or prolongation of existing hospitalisation

• results in persistent or significant disability or incapacity

• is a congenital anomaly or birth defect

• is any other important medical condition that, although not included in the above, may require medical or surgical intervention to prevent one of the outcomes listed.

All SAEs were recorded by recruitment centre staff on the trial SAE reporting form and e-mailed to a secure NHS.net account, which was accessed only by the research team within 24 hours of the investigator becoming aware of the SAE. Once the information was received, causality and expectedness were confirmed by the chief investigator. SAEs deemed unexpected and related to the trial were notified to the Research Ethics Committee within 15 days. All such events were reported to the Trial Steering Committee (TSC) and Data and Safety Monitoring Committee (DSMC) at their next meetings.

Some AEs were foreseeable as part of the proposed treatment – including those that met the definition of ‘serious’ as described above – and did not need to be reported immediately to the UKSTAR central office, provided that they were recorded in the ‘complications’ section of the CRF or participant questionnaire. These events were re-rupture, blood clots/emboli, pressure areas/hindfoot pain, falls and neurological symptoms in the foot.

All participants experiencing a SAE were followed up as per protocol until the end of the trial.

All unexpected SAEs or suspected unexpected SAEs that occurred between the date of consent and the date of the 9-month follow-up time point were reported.

Blinding

As the type of rehabilitation used was clearly visible, participants could not be blinded to their treatment. In addition, the treating clinician was not blinded to the treatment but took no part in the post-injury assessment of the participants. The outcome data were collected and entered onto the trial central database via questionnaire by a research assistant or a data entry clerk in the trial central office, which reduced the risk of assessment bias.

Follow-up

The UKSTAR office staff contacted the participants directly for follow-up at 3, 6 and 9 months using the contact details that the participant had supplied. Participants were contacted by post, by e-mail or by short message service (SMS), according to their preference; if no response was received, they were telephoned. All follow-up contacts and attempted contacts were logged without personal identifying details.

Participants who had supplied an e-mail address were sent a link to an online questionnaire. Participants who had supplied a mobile phone number were sent the same link by SMS. Participants who had supplied both an e-mail address and a mobile phone number were sent the link via both mechanisms. If a participant did not respond to any of these initial approaches, they were sent a reminder 1 week later. If there was still no response after another week, the participant was sent a paper questionnaire. If the paper questionnaire was not returned within 2 weeks, UKSTAR office staff telephoned the participant. If the participant was uncontactable during working hours, attempts were made to telephone them during the evening, as many participants were of working age.

Participants who had specified that they preferred to be contacted by post, or who had not supplied an e-mail address or mobile phone number, were sent a questionnaire in the post and sent a second postal questionnaire if no response was received within 2 weeks. UKSTAR office staff attempted to telephone the participant for follow-up if the second postal questionnaire was not returned within 2 weeks.

Deep-vein thrombosis, PE and re-rupture were reported by participants through completing a questionnaire or directly to the study office, or by recruitment centre staff after participants had returned to the centre for further treatment. These reports underwent validation, as follows. In the case of a patient-reported DVT or PE, recruitment centres were requested to complete a DVT/PE form, which detailed symptoms, results of any ultrasonography, results of any computerised tomography pulmonary angiogram imaging, treatment received and treatment duration. In the case of a patient-reported re-rupture, recruitment centres were requested to provide details of diagnosis and treatment. If the patient underwent surgery for a re-rupture, an operation note was requested. All information submitted in connection with a re-rupture was reviewed by the chief investigator, blinded to the treatment allocation, to confirm the diagnosis.

Sample size

The minimum clinically important difference (MCID) for the primary outcome ATRS was 8 points. At an individual patient level, a difference of 8 points represents the ability to walk upstairs or run with ‘some difficulty’ compared with ‘great difficulty’. At a population level, 8 points represents the difference between a ‘healthy patient’ and a ‘patient with a minor disability’. 32

In previous work, the standard deviation (SD) of the ATRS at 9 months post injury was 20 points. 34 Assuming a likely population variability of 20, MCID value of 8 and 90% power to detect the selected MCID, 264 participants needed to be randomised. Allowing a margin of 20% loss of primary outcome data to include patients who would cross over between interventions and those lost to follow-up led to a requirement of 330 participants. We intended to recruit a minimum of 330 patients from at least 22 centres over 16 months. The trial reached its primary recruitment target of 330 participants before the end of the proposed recruitment window and therefore the sample size was recalculated based on a larger population variability equivalent to a SD of 25 points, following a blinded review of the variability by the DSMC. As per Table 1 calculations for a SD of 25, MCID value of 8, 5% two-sided tests and 20% loss to follow-up, 516 participants were required. The maximum number of participants to be recruited for the trial was set at 550.

Statistical analysis

Health economics methods

Data management

In accordance with the standard operating procedures of the OCTRU, data management procedures were defined in a data management plan. This covered trial databases and data handling, definition of critical data fields, forms and questionnaires used, data collection, how protocol deviations were recorded, data rulings, handling data deviations, data security and confidentiality, data set closure, archiving and data sharing. Each data management plan version was signed off by the chief investigator and the trial statistician.

The monitoring plan determined the need for central and on-site data monitoring. All recruitment centres were monitored centrally. The monitoring plan specified that on-site monitoring was not required for this trial and no monitoring visits were conducted.

Statistics on data collection, data entry and query management were presented at each TMG meeting for oversight.

UK legislation requires data to be anonymised as soon as it is practical to do so. Participants were identified only by their initials and a participant number on UKSTAR questionnaires and in the study database. All documents were stored securely and accessible only by study staff and authorised personnel. Personal data and sensitive information required for the study were collected directly from trial participants and hospital notes. All personal information received in paper format for the trial was held securely and treated as strictly confidential. Personal data were stored separately from study outcomes in lockable cabinets in secure keycard-accessed rooms in the Kadoorie Centre in the John Radcliffe Hospital and in the Botnar Research Centre, University of Oxford. All paper and electronic data will be retained for at least 5 years after completion of the trial.

Patient and public involvement

The UKSTAR TSC and TMG both included a patient representative as a PPI member. Mrs S Webb was TSC PPI representative and attended meetings from the initial meeting and Mr R Grant was PPI representative at TMG meetings from September 2017.

Ethics approval and monitoring

Summary of changes to the trial protocol

All protocol versions can be found on the NIHR Journals Library website at www.journalslibrary.nihr.ac.uk/programmes/hta/1311562/#/ (accessed 11 November 2019).

The changes to the project protocol are summarised in Table 4.

Study participants

Patients with an Achilles tendon rupture typically attend the emergency department at their local hospital and, following their diagnosis, are referred to the next available fracture/trauma clinic to discuss the management of their injury.

The flow of participants through the study is summarised in Figure 1. This includes details on the total number of patients referred to the trauma clinic with an Achilles tendon rupture and those randomised. The availability of the primary outcome for analysis is also reported by treatment group, as is the total number of patients excluded from the primary outcome analysis.

FIGURE 1.

The UKSTAR CONSORT flow diagram. a, Two additional patients were randomised in error without giving consent to be in the study. These participants were excluded from all data analyses. Reproduced from Costa et al. 49 © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: http://creativecommons.org/licenses/by/4.0/.

Reproduced from Costa et al. 49 © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: http://creativecommons.org/licenses/by/4.0/.

Recruitment

A total of 1076 eligible participants were screened from July 2016 to May 2018 from 39 NHS hospitals across England and Scotland (see Figure 1). Of these, 540 participants consented to take part in the trial. Reasons why patients were not included in the trial are presented. Participants attended clinic visits at the time of randomisation (baseline) and at the 8-week follow-up. Participants were also contacted by the trial team by post, e-mail or telephone to complete follow-up questionnaires at 3, 6 and 9 months post injury. Two participants were randomised in error before consenting and are therefore not included in the numbers allocated to each treatment group.

Baseline characteristics

The randomisation was stratified by centre, and the allocation of participants to the treatment groups in each centre and the overall numbers is given in Table 5. The descriptive characteristics of the participants included in the ITT population are summarised by treatment group and overall in Table 6. These values are presented as numbers and percentages for categorical factors and as means and SD or medians and IQR, as appropriate, for continuous variables. These variables all appear well balanced between the two treatment groups. The distribution of participant ages by sex at enrolment is shown in Figure 2. This distribution has a peak in male patients aged 30–40 years and in female patients aged 40–60 years. Baseline values of patient-reported outcome measures (PROMs), ATRS and EQ-5D-5L are summarised by group in Table 7. ATRS values range from 0 to 100, with lower scores indicating more functional limitations; EQ-5D utility scores range from –0.511 to 1, with higher scores indicating better QoL and 0 being equivalent to death; and EQ-5D VAS scores range from 0 to 100, with higher scores indicating better QoL. The values reported are similar in the two treatment groups.

FIGURE 2.

Participant age (years) at randomisation by sex. (a) Male; and (b) female.

Compliance

Participant compliance with treatment is presented in Table 8. The population compliant with treatment for ≥ 6 weeks was made up of 477 (88.2%) participants overall, 212 (79.7%) of whom were in the plaster cast group and 265 (96.7%) of whom were in the functional brace group. The numbers of patients compliant with treatment for ≥ 4 weeks and ≥ 2 weeks are also listed in Table 8.

Details of the treatment received following randomisation are listed in Table 9. There were 247 (92.9%) participants in the plaster cast group and 269 (98.2%) who received their allocated treatment immediately at baseline. Those who did not receive the allocated treatment at baseline received the other treatment instead or withdrew. A further 35 participants (13.2%) in the plaster cast group and 4 (1.5%) in the functional brace group changed from the treatment to which they were randomised within the first 6 weeks and received the other treatment or surgery instead. The reasons why participants changed from their allocated treatment are listed in Table 10 and include patient decision, clinician decision, medical resources unavailable, incorrect Achilles tendon rupture diagnosis, surgery and withdrawal.

Details of the treatment received in each group, including time point when the patient was allowed to fully bear weight, time point when cast/brace was removed, number of cast changes, type of brace used, number of heel wedges and VTE prophylaxis are listed in Table 11. The data collected show that the number of participants allowed to bear weight early was larger in the functional brace group than in the plaster cast group. Proportions of these patients are listed for each treatment group and are restricted to patients who did not change from their allocated treatment in the first 6 weeks following randomisation.

There were no differences between the two treatment groups in the time point when the plaster cast or functional brace was removed. On average, patients in the plaster cast group changed their plaster cast three times during the treatment period. The most frequently used functional brace make was Aircast (44.5%) and the median number of heel wedges was three, although the number varied from zero to five, depending on time point. VTE prophylaxis was offered to more patients in the plaster cast group (n = 187, 70.3%) than in the functional brace group (n = 158, 57.7%). The VTE treatments used were low-molecular-weight heparin and oral anticoagulant in similar proportions in the two groups.

Numbers analysed

The ITT population comprised all patients who were randomised and gave consent to participate in the trial. These patients were analysed in the group to which they were allocated, including in the analysis of PROMs. Data for the two randomised participants who did not give their consent were excluded from the analysis. The ITT population was made up of 540 participants overall, 266 of whom were in the plaster cast group and 274 of whom were in the functional brace group. Analyses of all primary and secondary outcomes were performed for this population.

The CACE population35 comprised all randomised participants who were compliant with treatment for ≥ 6 weeks.

Withdrawals

Table 12 provides the available data at each follow-up time point, including the number of CRFs and PROs and the number of participants who withdrew or died, according to treatment group. There was a good completion rate of CRFs and PROs across both treatment groups throughout the study period. In total, 10 patients withdrew (seven from the plaster cast group and three from the functional brace group). There were two deaths, both in the functional brace group. Reasons for withdrawal are listed in Table 13; these include clinician decision, patient decision and private treatment.

Analyses to address primary outcome

The primary outcome in this study is the ATRS measured at 9 months post injury, as described in the statistical analysis plan.

Achilles Tendon Rupture Score was assessed at baseline (pre injury), 8 weeks and 3, 6 and 9 months after the tendon rupture. The mean ATRS score and SD for each treatment group at each time point are provided in Table 14. The mean ATRS differences between the treatment groups was estimated based on a linear mixed-effects regression model both unadjusted and adjusted for the stratification factors age, sex and baseline ATRS as fixed effects, and recruitment centre and observations within participants as random effects. The adjusted analysis was prespecified as the principal analysis of the trial results.

The adjusted analysis showed no statistically significant difference in ATRS between the treatment groups at 9 months (–1.38, 95% CI –4.9 to 2.1). The 8-week follow-up results show a statistically significant difference in the ATRS in favour of the functional brace group (5.53, 95% CI 2.0 to 9.1); however, this effect fades during the 9-month follow-up. The marginal mean ATRS values from the mixed-effects model are presented from the 8-week follow-up to the 9-month follow-up in Figure 3.

FIGURE 3.

Marginal mean ATRS values from the mixed-effects model and associated 95% CIs for the two treatment groups pre injury to 9 months post injury. ATRS values range from 0 to 100, with higher scores indicating better outcome.

Supplementary fully adjusted analyses were carried out, accounting for further predefined prognostic variables, and included age, sex, baseline ATRS, diabetes mellitus and smoking status as fixed effects, with random effects for centre and observations within participant (Table 15). These results showed a similar between-group difference to those results of the primary analysis at 9 months post injury (–1.15, 95% CI –4.7 to 2.4).

Analyses to address secondary outcomes

The secondary outcomes collected and analysed in the UKSTAR were EQ-5D-5L and complications evaluated at 8 weeks and 3, 6 and 9 months after the injury.

EuroQol-5 Dimensions, five-level version

The EQ-5D-5L was analysed as a continuous outcome using the utility score values from the five-level questions and based on the reported EQ-5D VAS. Summary results for the EQ-5D utility score and EQ-5D VAS are reported for each treatment group at each time point in Table 16, together with the unadjusted and adjusted mixed-effects model estimates. The analyses for both EQ-5D utility score and EQ-5D VAS are presented graphically in Figures 4 and 5. Both EQ-5D scores show a trend of improvement over time. The EQ-5D utility score analysis showed a statistically significant difference at the 8-week follow-up in favour of the functional brace group (0.069, 95% CI 0.03 to 0.1), but this difference was no longer present by the 9-month post injury follow-up.

TABLE 16 - EuroQol-5 Dimensions utility and EQ-5D VAS mixed-effects model results at 8 weeks and at 3, 6 and 9 months post injury (ITT population)

Analysis adjusted for site, age, sex and EQ-5D baseline pre injury, with repeated observations for each participant.

Reproduced from Costa et al. 49 © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: http://creativecommons.org/licenses/by/4.0/.

EQ-5D	Plaster cast group (N = 266)	Functional brace group (N = 274)	Between-group difference (95% CI)		p-value
			Unadjusted	Adjusteda
EQ-5D utility
Baseline post injury, median (IQR), n	0.242 (0.02–0.47), 264	0.282 (0.03–0.52), 273	0.042 (0.01 to 0.08)	0.041 (0.01 to 0.07)	0.017
8 weeks, mean (SD), n	0.588 (0.23), 234	0.7 (0.18), 241	0.066 (0.03 to 0.1)	0.069 (0.03 to 0.1)	0.000
3 months, mean (SD), n	0.638 (0.22), 229	0.669 (0.19), 245	0.031 (–0.01 to 0.07)	0.035 (0.0 to 0.07)	0.056
6 months, mean (SD), n	0.766 (0.15), 224	0.757 (0.18), 237	–0.009 (–0.05 to 0.03)	–0.002 (–0.04 to 0.03)	0.916
9 months, median (IQR), n	0.829 (0.72–0.91), 244	0.795 (0.72–0.88), 259	–0.010 (–0.05 to 0.03)	–0.009 (–0.04 to 0.03)	0.623
EQ-5D VAS, median (IQR), n
Baseline post injury	90.0 (80–95), 263	90.0 (80–95), 273	0.77 (–2.18 to 3.72)	1.28 (–1.4 to 3.97)	0.349
8 weeks	75.0 (60–85), 234	75.0 (65–85), 240	1.08 (–2.05 to 4.2)	1.61 (–1.21 to 4.43)	0.264
3 months	80.0 (65–85), 229	80.0 (65–90), 245	1.29 (–1.84 to 4.42)	1.66 (–1.16 to 4.48)	0.249
6 months	81.5 (70–90), 224	80.0 (70–90), 236	0.49 (–2.69 to 3.66)	1.08 (–1.77 to 3.93)	0.458
9 months	86.0 (80–92), 242	85.0 (75–91), 259	–0.76 (–3.8 to 2.28)	–0.56 (–3.32 to 2.2)	0.693

FIGURE 4.

Marginal mean EQ-5D utility values from the mixed-effects model and associated 95% CIs for the two treatment groups from baseline (post injury) to 9 months.

FIGURE 5.

Marginal mean EQ-5D VAS values from the mixed-effects model and associated 95% CIs for the two treatment groups from baseline (post injury) to 9 months.

Ancillary analyses

Following a presentation of the preliminary results, the TSC wanted to explore where the apparent differences at 8 weeks in EQ-5D utility score came from. The individual domains of the EQ-5D were explored using box plots in Figures 18–21 (see Appendix 3). The median score is marked with a triangle, whiskers are IQRs and the individual dots and crosses mark the outliers. The differences at 8 weeks appear to lie in the ability to self-care and usual activities only. Furthermore, in keeping with the health economics analysis plan, the distribution of the responses to the EQ-5D-5L questionnaires by treatment group and assessment point is presented in Appendix 4. That analysis showed no significant differences in the proportions of individuals reporting suboptimal health [i.e. any functional (below level 1) impairment] within dimensions between the two treatment groups at each time point.

Adverse events

Foreseeable AEs were reported as complications in Analyses to address secondary outcomes.

Two deaths were reported in this study, one of which was a SAE. This was due to a known lung cancer condition and was unrelated to the Achilles injury. The second death was due to a cardiac arrest following a bilateral PE and, as judged by the investigators, was potentially related but not unexpected. Both deaths were in the functional brace group.

Results of economic analysis

Table 20 shows the degree of missing health economic data by treatment group and follow-up time point. The missing data pattern is non-monotonic, as individuals with missing data at one follow-up time point could return to the trial subsequently. For example, there are more missing EQ-5D data at 6 months than at 9 months post injury. A similar pattern can be observed for economic costs. It is worth noting that the smaller number of participants with complete data for the entire duration of follow-up (baseline to 9 months post injury) was because of a strict application of the term missing (i.e. we considered a participant as having incomplete data if, for example, they responded positively to vising a GP surgery at 3 months but did not specify the number of consultations, despite all other resource use items being completed). However, for the cost-effectiveness analysis, imputation was not at the aggregate level, such that most of the data used for the analysis were based on actual participant responses.

Cost-effectiveness results

The cost-effectiveness results are presented in Table 22, with plaster cast as the referent and functional brace as the comparator (i.e. functional brace minus plaster cast) for the estimation of ICER values. The analytic time horizon is the entire 9-month post-injury follow-up period of the trial. The joint distribution of costs and outcomes for the base-case analysis and sensitivity analyses is represented in Figures 6–13.

TABLE 22 - Cost-effectiveness: cost per QALY (2017 prices) – functional brace compared with plaster cast

SE, standard error.

Given the pattern of results, plaster cast has been selected as the referent and functional brace as the comparator (i.e. functional brace minus plaster cast) for the estimation of ICER values. Dominance indicates that average costs were lower and average benefits were greater for functional brace vs. plaster cast.

Probability cost-effective if cost-effectiveness threshold set at £15,000 per QALY, with the exception of the sensitivity analysis using ATRS as the health outcome measure of interest. In the latter case, this refers to probability of cost-effectiveness if cost-effectiveness threshold is set arbitrarily at £100 per unit gain in ATRS score.

Probability cost-effective if cost-effectiveness threshold set at £20,000 per QALY, with the exception of the sensitivity analysis using ATRS as the health outcome measure of interest. In the latter case, this refers to probability of cost-effectiveness if cost-effectiveness threshold is set arbitrarily at £300 per unit gain in ATRS score.

Probability cost-effective if cost-effectiveness threshold set at £30,000 per QALY, with the exception of the sensitivity analysis using ATRS as the health outcome measure of interest. In the latter case, this refers to probability of cost-effectiveness if cost-effectiveness threshold is set arbitrarily at £500 per unit gain in ATRS score.

NMB if cost-effectiveness threshold set at £15,000 per QALY, with the exception of the sensitivity analysis using ATRS as the health outcome measure of interest. In the latter case, this refers to NMB if cost-effectiveness threshold is set arbitrarily at £100 per unit gain in ATRS score.

NMB if cost-effectiveness threshold set at £20,000 per QALY, with the exception of the sensitivity analysis using ATRS as the health outcome measure of interest. In the latter case, this refers to NMB if cost-effectiveness threshold is set arbitrarily at £300 per unit gain in ATRS score.

NMB if cost-effectiveness threshold set at £30,000 per QALY, with the exception of the sensitivity analysis using ATRS as the health outcome measure of interest. In the latter case, this refers to NMB if cost-effectiveness threshold is set arbitrarily at £500 per unit gain in ATRS score.

Range from 0 to 100, with higher scores indicating better outcomes.

Reproduced from Costa et al. 49 © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: http://creativecommons.org/licenses/by/4.0/.

Scenario	Treatment group, mean (SE) cost (£)		Incremental cost (95% CI)	Treatment group, mean (SE) QALY		Incremental QALYs (95% CI)	ICERa (£)	Probability that functional brace is cost-effective			NMBs
	Functional brace	Plaster cast		Functional brace	Plaster cast			p-valueb	p-valuec	p-valued	NMBe (95% CI)	NMBf (95% CI)	NMBg (95% CI)
Base-case analysis
Imputed attributable costs and QALYs; covariate adjusted	1078.16 (83.42)	1180.72 (89.63)	–102.56 (–289.28 to 84.16)	0.506 (0.0064)	0.492 (0.0066)	0.015 (–0.0013 to 0.030)	Dominant	0.963	0.965	0.966	312.28 (–31.26 to 655)	383.82 (–32.67 to 793.80)	526.90 (–42.50 to 1076.87)
Sensitivity analyses
Complete-case attributable costs and QALYs; covariate adjusted	948.77 (53.91)	1117.28 (110.66)	–168.51 (–458.01 to 32.88)	0.513 (0.00642)	0.497 (0.0064)	0.017 (–0.0035 to 0.037)	Dominant	0.976	0.976	0.972	443.54 (19.83 to 933.22)	527.26 (9.11 to 1094.07)	694.70 (–17.56 to 1406.23)
Societal perspective	4362.15 (348.71)	4114.54 (292.18)	247.61 (–476.44 to 971.66)	0.506 (0.0063)	0.502 (0.007)	0.015 (–0.0042 to 0.031)	16,510	0.501	0.576	0.688	–29.65 (–991.50 to 874.93)	44.36 (–964.19 to 991.46)	192.39 (–926.97 to 1244.53)
CACE population	1038.6 (62.89)	1169.44 (78.48)	–130.84 (–335.38 to 90.36)	0.510 (0.00609)	0.488 (0.00688)	0.022 (0.0051 to 0.038)	Dominant	0.992	0.993	0.994	44.52 (89.86 to 852.63)	57.36 (127.50 to 1030.39)	818.02 (199.26 to 1434.03)
Secondary cost-effectiveness analysis using ATRSh as outcome measure	1057.22 (71.91)	1149.44 (79.25)	–92.21 (–273.86 to 89.44)	45.09 (0.72)	44.30 (0.73)	0.78 (–1.12 to 2.69)	Dominant	0.875	0.839	0.822	174.03 (–117.37 to 463.44)	328.84 (–306 to 970.91)	406.25 (–403.75 to 1218.76)

FIGURE 6.

Cost-effectiveness scatterplot at 9 months for base-case analysis (NHS and PSS perspective, imputed, additionally controlled for pre-injury utility, ITT analysis). Reproduced from Costa et al. 49 © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: http://creativecommons.org/licenses/by/4.0/.

Reproduced from Costa et al. 49 © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: http://creativecommons.org/licenses/by/4.0/.

FIGURE 7.

Cost-effectiveness acceptability curve at 9 months for base-case analysis (NHS and PSS perspective, imputed, additionally controlled for pre-injury utility, ITT analysis). Reproduced from Costa et al. 49 © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: http://creativecommons.org/licenses/by/4.0/.

Reproduced from Costa et al. 49 © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: http://creativecommons.org/licenses/by/4.0/.

FIGURE 8.

Cost-effectiveness scatterplot at 9 months for complete cases (NHS and PSS perspective, ITT analysis).

FIGURE 9.

Cost-effectiveness acceptability curve for complete cases (NHS and PSS perspective, ITT analysis).

FIGURE 10.

Cost-effectiveness scatterplot for societal perspective (imputed, ITT analysis).

FIGURE 11.

Cost-effectiveness acceptability curve for societal perspective (imputed, ITT analysis).

FIGURE 12.

Cost-effectiveness scatterplot for CACE population (imputed, NHS and PSS perspective).

FIGURE 13.

Cost-effectiveness acceptability curve for CACE population (imputed, NHS and PSS perspective, covariate adjusted).

Base-case analysis

Patients in the functional brace group experienced a non-statistically significant increase in QALYs in the base case (0.015 QALYs, 95% CI –0.0013 to 0.030 QALYs) over the 9-month follow-up period. In addition, mean NHS and PSS costs were lower in the functional brace group (mean cost difference –£103, 95% CI –£289 to £84). The ICER for the base-case analysis indicates that functional brace is the dominant procedure, as average costs for this intervention were lower and average benefits were greater than those for plaster cast.

Assuming cost-effectiveness thresholds of £15,000 per QALY, £20,000 per QALY and £30,000 per QALY, respectively, the probability that functional brace was cost-effective ranged from 0.96 to 0.97, and the NMB associated with functional brace was positive (see Table 22).

Sensitivity analyses

Comparing mean costs and QALY estimates using different analytical scenarios (complete case, societal perspective and CACE population) revealed that the cost-effectiveness results generally supported the base-case finding, with the exception of the sensitivity analysis that adopted a societal perspective. From the societal perspective, mean costs were higher in the functional brace group (£248, 94% CI –£476 to £972). However, the QALY results followed the same pattern as that for the base-case analysis and indicated that participants in the functional brace group experienced a non-statistically significant increase in QALYs over the 9-month follow-up period (0.015 QALYs, 95% CI –0.0042 to 0.031 QALYs). The probability that functional brace was cost-effective declined to a range of 0.50–0.69 at cost-effectiveness thresholds of £15,000 per QALY, £20,000 per QALY and £30,000 per QALY. The results of the mixed-effects model followed a similar pattern to those of the base-case (imputed) model: patients in the functional brace group experienced a non-statistically significant increase in QALYs (0.014 QALYs, 95% CI –0.0018 to 0.031 QALYs) over the 9-month follow-up period. In addition, mean NHS and PSS costs were lower in the functional brace group (mean cost difference –£135, 95% CI –£342 to £71).

The results of the sensitivity analyses to the MAR assumption, presented in Appendix 1, indicate that the cost-effectiveness of functional brace remained stable across all of the MAR departure scenarios. In addition, Figure 17 shows that a change in cost-effectiveness decision is likely to occur if participants with missing HRQoL data have up to 50% lower HRQoL than trial participants with similar characteristics whose HRQoL data are available.

Recruitment

A total of 375 patients screened were found to be ineligible for the trial. The most common reason for being ineligible (n = 155) was presenting > 14 days after the Achilles tendon injury. Late presentation after an Achilles tendon rupture is not uncommon. Although a patient may have severe pain when the tendon ruptures, this acute pain usually settles quickly and the patient can often put weight through their leg, albeit without being able to walk normally. Some patients feel that they would not be able to walk at all if they had suffered a ‘serious’ injury and therefore continue to try to mobilise on their leg before eventually seeking treatment some time later, when their ability has not improved. The cut-off point of 14 days used to define an ‘acute’ rupture is somewhat arbitrary but in keeping with definitions used in previous research into this injury. Patients presenting at later times may have partial or complete healing of the tendon but often with tendon lengthening, which restricts their function. As the treatment of late presentation injuries is not straightforward and often requires surgical intervention, these patients were excluded from this trial of acute non-operative management.

The second common reason why patients were ineligible (n = 120) was that they chose to have surgery. This number is perhaps smaller than had been anticipated when UKSTAR was designed and, to some degree, accounts for the faster than expected rate of recruitment. However, it is in keeping with the worldwide trend towards non-operative treatment of acute rupture of the Achilles tendon, as per the recent evidence base, which suggests little functional advantage of surgery. 8,9

Only 46 patients were excluded because they were unable to adhere to trial procedures or complete questionnaires, most commonly because they could not read written English, which was used in the follow-up questionnaires. Thirty-seven patients were excluded because they had suffered a previous Achilles tendon injury, which was likely to have affected their baseline, pre-injury function. Achilles tendon rupture is very rare in children and hence it is not surprising that only three patients were excluded because they were aged < 16 years. The remaining 14 patients were excluded by recruitment centres under the heading ‘other’; we did not record details of these individual cases.

Of the 1076 potentially eligible patients screened across the 39 recruitment centres, 540 consented to enter the trial. Ninety-nine patients were not approached about the trial because no research associate was available to discuss the trial (n = 97), usually because the patient had presented at the weekend or because no functional brace was available at the time of presentation (n = 2). A further 50 patients were not offered the opportunity to take part in the trial because of a clinician decision. In some cases, specific reasons were given for this decision, for example ‘active treatment of a local skin lesions precluding the use of a cast’, but in other cases the clinician did not provide a reason. Therefore, a total of 149 potentially eligible patients were never offered the opportunity to take part in the trial. This reduced the number of participants but is unlikely to have caused selection bias.

Of the 927 patients who had the opportunity to take part, 385 declined. Patients may decline to take part in a trial for various reasons. Those who do not want to be part of any research – often because of the perception, or indeed the reality, of filling out extra, onerous questionnaires – are unlikely to adversely affect the trial in terms of the difference between treatment groups. However, those who decline because they have a preference for one treatment over another do create selection bias. In this trial, it is reassuring that 540 out of the 927 patients who were offered the opportunity to take part in the trial (58%) agreed to participate.

Participants and interventions

The two groups of participants were well balanced in terms of baseline pre-injury characteristics.

In keeping with the epidemiology of Achilles tendon rupture, more men were aged 30–40 years, whereas women were a little older at the time of their injury, with the age range of 40–60 years being most common. Sports accounted for the great majority of ruptures (70.4%) and relatively few patients declared predisposing risk factors; only 4.3% of participants had diabetes mellitus and 3.9% were taking steroids, these being associated with an increased risk of tendon rupture. Only 3.7% declared a pre-existing Achilles tendinopathy, despite the fact that histological studies indicate that degenerative changes are almost always present on biopsies taken from tendons immediately after an injury. 4,5

The median pre-injury ATRS score was 100 in both groups, indicating normal Achilles function. Similarly, the median EQ-5D utility score was 1, indicting perfect health. This, and the fact that the large majority of participants were employed or self-employed, suggests that most Achilles ruptures affect working-age people with good pre-injury health. In studies of acute injury, it is necessary to collect functional and QoL data by recall, in this case as part of the baseline post-injury clinical reporting form. Although some recall bias/response shift is inevitable, there is no alternative in this sort of trial. In clinical areas in which pre-injury QoL is much more variable than for patients with Achilles tendon rupture, we have demonstrated that recall estimates of QoL still agree with age- and sex-matched controls. 50 However, the characteristics of the participants reflect that Achilles rupture affects all age groups, with both men and women in their 80s represented in the trial. Overall, the participants in the trial are representative in terms of demographics of previously reported patients with this injury.

We anticipated some crossover between the treatment groups following the random allocation, but in fact this was relatively uncommon. Only one participant decided to have a cast after having been allocated a functional brace. Thirteen participants decided to change to a functional brace after having been allocated a cast, which may reflect the perception that the brace made mobilisation easier. However, the numbers were small and we did not formally investigate the qualitative aspects of the decision to change treatment. Two further participants withdrew from the trial immediately after randomisation and seven others crossed over treatment groups for what were described as clinical or unknown reasons. Given the small number of crossovers at baseline, these are very unlikely to have influenced the results of the trial.

In terms of compliance with treatment once implemented, the trial protocol stipulated that patients would be deemed compliant if they maintained their allocated treatment for a minimum of 6 weeks. The choice of 6 weeks reflects the fact that this was the time at which weight-bearing would usually be permitted for those patients in a cast, those in a functional brace generally being fully weight-bearing from the outset. Overall, 88% of participants were fully compliant. However, compliance was higher in the functional brace group (97%) than in the plaster cast group (80%). This may reflect participants’ desire to have the cast removed as soon as possible (most of these participants used a functional brace for a further 2 weeks or longer), but we did not interview participants about the reasons why they changed treatment after 6 weeks.

Some patients did, of course, change treatment before 6 weeks, having initially accepted their allocated intervention. This was more common in the plaster cast group; 11.3% changed to a functional brace, compared with the 0.4% allocated a functional brace who changed to a plaster cast. This may also suggest that functional brace was preferred but, although we asked these participants if they or the clinician treating them chose or recommended changing treatment, we were not able to formally explore the reasons behind decisions to change treatment. An additional 3% of participants chose to have surgery before 6 weeks (1.9% in the plaster cast group and 1.1% in the functional brace group). In some cases, these participants described another fall or injury to their tendon. However, we have not reported these as ‘re-ruptures’ of the tendon on the basis that the tendon was unlikely to have healed before 6 weeks.

One other notable element of participants’ treatment beyond the treatment allocation was the use of VTE prophylaxis. Patients with Achilles tendon rupture are at increased risk of VTE, as the injury defunctions the triceps surae muscles, which are an important part of the calf muscle pump that helps to return venous blood to the heart. In the plaster cast group, 70% of patients had VTE prophylaxis, most commonly self-administered low-molecular-weight heparin injections. Fewer patients (58%) had VTE prophylaxis in the functional brace group. This difference may reflect the belief that patients who are able to fully weight bear in a functional brace are at lower risk of VTE than those with restricted weight-bearing in a cast, but this trial was not designed to address questions related to the management of VTE.

Results

In total, 93.3% of participants completed the primary outcome measure 9 months after their Achilles tendon rupture: 91.7% in the plaster cast group and 94.9% in the functional brace group. Therefore, loss to follow-up was considerably lower than the 20% accounted for in the trial design, which, alongside the fact that the trial was able to recruit more patients than the minimum of 330 required by the sample size calculation, ensures that the trial had considerably more than 90% power.

Follow-up was also good at other time points, with 88%, 88% and 86% of participants completing questionnaires at 8 weeks, 3 months and 6 months, respectively.

Health economics evaluation

The mean direct intervention costs were £36 for the plaster cast group and £109 for the functional brace group. The higher upfront cost of the functional brace (mean difference £73) was statistically significant. However, by 8 weeks this difference had reversed, such that the mean total NHS and PSS costs were significantly lower in the functional brace group. The difference was driven mostly by the greater number of outpatient appointments required in the plaster cast group.

This is an important finding, as it will reassure the finance teams in trauma and orthopaedic departments that, despite the extra initial cost of a functional brace, they will reduce their overall costs when treating patients with an Achilles tendon rupture.

The mean total NHS and PSS costs during the entire follow-up period were £1183 for the plaster cast group and £1018 for the functional brace group. Although functional brace was marginally cheaper, the mean between-group cost difference of £164 was not statistically significant.

In terms of HRQoL, the mean QALY value was, on average, marginally higher for the functional brace group among complete cases and in the sensitivity analyses, although this mean QALY difference was not statistically significant.

Therefore, as the functional brace group incurred slightly lower costs and achieved slightly better QoL over the course of the study, in health economic terms, functional brace is the dominant intervention.

In summary, the health economic evaluation indicates that functional brace is very likely to be cost-effective.

Limitations

A concern at the start of the study was that patients would not be willing to take part in a trial comparing two interventions that needed to be worn for a prolonged period of time. Some of the 385 patients who declined did so because they did not want to be part of a research project. These patients, although undoubtedly affecting the external validity of the trial, are unlikely to create selection bias when comparing the two interventions. By contrast, those who declined because they had a preference for one treatment over another do create selection bias. However, in total, 540 of the 927 patients who were offered the opportunity to take part in the trial (58%) agreed to participate, so we can be confident that the participants in the trial are broadly representative of the population of patients having non-operative treatment for acute rupture of the Achilles tendon.

A further anticipated limitation was crossover from the allocated treatment and, indeed, 14 patients did not receive their allocated intervention after being randomised. There were also some cases of incomplete compliance with treatment. The ability to bear weight immediately using a functional brace may have triggered a desire to change treatment, given that the majority changed from the plaster cast group to the functional brace group. However, the overall number is small for a trial of this size and the CACE analysis, that is the analysis adjusted for incomplete compliance, confirmed the result of the primary analysis (i.e. there was no evidence of a difference between the two groups of participants at 9 months post injury).

Loss to follow-up is another potential limitation. However, > 93% of participants provided primary outcome data at 9 months, which is considerably higher than the 80% assumed in the trial design. Therefore, given that the trial also exceeded the minimum sample size by some margin, we can be confident that the conclusions are robust and the risk of type II error is very low.

UKSTAR study team

Chief investigator: Matthew Costa.

Co-investigators: Matthew Costa, Juul Achten, Rebecca Kearney, Sarah Lamb, Nick Parsons, Stavros Petrou, Ben Ollivere, Malvenia Richmond and Richard Grant.

Study lead: Juul Achten.

Trial managers: Susan Wagland and Anna Liew.

Senior trial managers: Juul Achten and Damian Haywood.

Study co-ordinators and administrators: Catherine Thompsett, Ramona Barbu, Kylea Draper, Hugo Strachwitz, Hasina Mangal and Alice Brealy.

Health economists: Stavros Petrou and Mandy Maredza.

Study statisticians: Michael Maia Schlüssel, Ioana Marian and Susan Dutton.

Recruitment centres

Study Steering Committees

The TSC comprised:

• Independent members: Mr Paul Baker (Orthopaedic Surgeon), chairperson; Mrs Sarah Webb (Patient Representative); Dr Dylan Morrissey (Consultant Physiotherapist); and Dr Anne-Marie Hutchison (Consultant Physiotherapist).

• Non-independent member: Professor Matthew Costa (Chief Investigator).

The DSMC comprised:

• Independent members: Professor Lee Shepstone (Statistician), chairperson; Professor Simon Donell (Orthopaedic Surgeon); and Dr Jean Craig (Reseach Advisor).

• Non-independent members: Ioana Marian (Trial Statistician) and Susan Dutton (OCTRU lead statistician).

Contributions of authors

Matthew L Costa (https://orcid.org/0000-0003-3644-1388) (Professor of Trauma Surgery, Oxford Trauma) was chief investigator. He led the funding application, study conception and design, development of interventions, provided overall study supervision, and wrote and reviewed the report.

Juul Achten (https://orcid.org/0000-0002-8857-5743) (Research Manager, Oxford Trauma) prepared the funding application, provided overall study supervision, developed the study, developed the intervention, designed the study, and wrote and reviewed the report.

Susan Wagland (https://orcid.org/0000-0002-5566-0925) (Clinical Trials Manager, Oxford Trauma) managed and supervised the study, and wrote and reviewed the report.

Ioana R Marian (https://orcid.org/0000-0002-0692-8112) (Medical Statistician) was trial statistician, conducted the statistical analysis and wrote the report.

Mandy Maredza (https://orcid.org/0000-0002-2030-3338) (Research Fellow, Health Economics) was trial health economist. She designed the study, conducted the health economics analysis and wrote the report.

Michael Maia Schlüssel (https://orcid.org/0000-0002-1711-9310) (Medical Statistician) was trial statistician. He conducted the statistical analysis and wrote the report.

Anna S Liew (https://orcid.org/0000-0002-6568-1631) (Clinical Trials Manager, Oxford Trauma) managed and supervised the study, developed the study, developed the intervention, designed the study and reviewed the report.

Nick R Parsons (https://orcid.org/0000-0001-9975-888X) (Associate Professor of Medical Statistics) developed the study, developed the intervention, designed the study and reviewed the report.

Susan J Dutton (https://orcid.org/0000-0003-4573-5257) (OCTRU Lead Statistician) was lead statistician. She designed the study, conducted the statistical analysis, and wrote and reviewed the report.

Rebecca S Kearney (https://orcid.org/0000-0002-8010-164X) [Associate (Clinical) Professor and Associate Director of Warwick Clinical Trials Unit] developed the study, developed the intervention, designed the study and reviewed the report.

Sarah E Lamb (https://orcid.org/0000-0003-4349-7195) (Professor and Director of Centre for Statistics in Medicine) developed study conception, designed the study and reviewed the report.

Benjamin Ollivere (https://orcid.org/0000-0002-1410-1756) (Clinical Associate Professor and Honorary Consultant Orthopaedic and Major Trauma Surgeon) developed the study, developed the intervention, designed the study and reviewed the report.

Stavros Petrou (https://orcid.org/0000-0003-3121-6050) (Professor of Health Economics) oversaw the health economics analysis, and wrote and reviewed the report.

Publications

Achten J, Parsons NR, Kearney RL, Maia Schlüssel M, Liew AS, Dutton S, et al. Cast versus functional brace in the rehabilitation of patients treated non-operatively for a rupture of the Achilles tendon: protocol for the UK study of tendo achilles rehabilitation (UK STAR) multi-centre randomised trial. BMJ Open 2017;7:e019628.

Marian I, Costa ML, Dutton S. Cast versus functional brace in the rehabilitation of patients with a rupture of the Achilles tendon: statistical analysis plan for the UK study of tendo Achilles rehabilitation (UK STAR) multi-centre randomised controlled trial. Trials 2019;20:311.

Costa ML, Achten J, Marian IR, Dutton SJ, Lamb SE, Ollivere B, et al. Plaster cast versus functional brace for non-surgical treatment of Achilles tendon rupture (UKSTAR): a multicentre randomised controlled trial and economic evaluation. Lancet 2020;395:441–8.

Data-sharing statement

All data requests should be submitted to the corresponding author for consideration. Access to available anonymised data may be granted following review.

Patient data

This work uses data provided by patients and collected by the NHS as part of their care and support. Using patient data is vital to improve health and care for everyone. There is huge potential to make better use of information from people’s patient records, to understand more about disease, develop new treatments, monitor safety, and plan NHS services. Patient data should be kept safe and secure, to protect everyone’s privacy, and it’s important that there are safeguards to make sure that it is stored and used responsibly. Everyone should be able to find out about how patient data are used. #datasaveslives You can find out more about the background to this citation here: https://understandingpatientdata.org.uk/data-citation.

Disclaimers

This report presents independent research funded by the National Institute for Health Research (NIHR). The views and opinions expressed by authors in this publication are those of the authors and do not necessarily reflect those of the NHS, the NIHR, NETSCC, the HTA programme or the Department of Health and Social Care. If there are verbatim quotations included in this publication the views and opinions expressed by the interviewees are those of the interviewees and do not necessarily reflect those of the authors, those of the NHS, the NIHR, NETSCC, the HTA programme or the Department of Health and Social Care.

Introduction

UKSTAR completed recruitment on schedule (Figure 23), with 540 participants recruited.

FIGURE 23.

UKSTAR actual and predicted recruitment.

Completeness of baseline and 8-week data and rates of follow-up at all time points were excellent, thanks to the dedication of clinicians and researchers at the recruitment centres and an experienced, dedicated, central trial management team.

Management milestones

Table 28 shows the dates when milestones in the project management plan were reached.

Recruitment target and recruitment centre selection

Principal investigators at potential recruitment centres were approached through the NIHR/Orthopaedic Trauma Society Research Network and British Orthopaedic Foot and Ankle Society. We included sites of all sizes (from major trauma centres to local emergency hospitals) from regions across England and Scotland.

Each potential recruitment centre completed a site feasibility questionnaire, which was reviewed by the chief investigator. Sites were asked to declare how many patients presented at their site with Achilles tendon rupture and were treated non-operatively, and their expected recruitment rate, which needed to be at least one participant per month. Some sites declined on the grounds that all of their patients had already been put into a functional brace, or were all treated with a plaster cast. Sites that were actively recruiting for another Achilles trial by our research group, the Platelet Rich Plasma in Achilles Tendon Healing (PATH-2) study,56 were not opened to UKSTAR until recruitment for PATH-2 was complete to avoid competition between trials for the same patients and potential recruitment bias.

UKSTAR opened to recruitment on 16 August 2016, 1 month later than planned as a result of contractual delays at recruitment centres. The original application predicted a recruitment rate of one participant per month per centre, which led to the conclusion that a minimum of 22 centres was required. However, during the first 6 months, although more recruitment centres were opened than planned (nine as opposed to six), recruitment in most centres was slower than expected (27 participants in total) and weighted towards a single, high-recruiting centre (Aberdeen, with 15 participants). We decided, therefore, to expand the number of recruitment centres and were successful in opening 39 recruitment centres, including some whose trauma departments were new to participating in trials.

One recruitment centre (James Paget University Hospitals NHS Foundation Trust, Norfolk) closed to recruitment early because of lack of research staff, having recruited no participants. All other recruitment centres recruited at least one participant.

The trial reached its original recruitment target of 330 participants in October 2017, 7 months ahead of schedule. The required sample had been estimated a priori to achieve 90% power in the primary outcome (ATRS at 9 months) and allowing for 20% loss to follow-up and crossovers. Crossover data, protocol deviations and outcome completion information were assessed prior to reaching the initial target. To avoid the power of the trial being compromised by potentially large numbers of crossovers and loss to follow-up at 9 months, we submitted, with the support of the DSMC and TSC, a substantial amendment to increase the sample size to a maximum of 550, and to recruit up to the original recruitment end date (31 May 2018). The trial continued recruiting until its original planned end date, recruiting 540 participants (see Figure 23).

Monitoring of trial recruitment

Recruitment centres were trained in recruitment procedures during site initiation visits, which were in person or by conference call. It was not necessary for trial staff to travel to distant recruitment centres if staff at those centres were experienced in trial recruitment. Staff at recruitment centres completed a monthly screening log, declaring all patients who had presented to the emergency department, specialist fracture clinic or foot and ankle clinic with Achilles tendon rupture. We monitored the reasons for non-recruitment, looking for trends at particular recruitment centres, and addressed them on a centre-by-centre basis. Recruitment centres were informed of how their recruitment rate compared with that of other recruitment centres in a monthly newsletter.

Data management

The data management plan defined the trial’s data management procedures in accordance with the trials unit’s standard operating procedures. The data management plan identified databases and information technology systems used by the trial, defined data types, data sharing and access, the critical data items, questionnaires and events, and the location of the trial data matrix; and described confidentiality, how protocol deviations were defined and what action to take, how source data were collected and entered at each time point, and how follow-up was managed. It recorded decisions on follow-up time windows made by the TMG, data rulings made by the chief investigator, statistician, health economist or trial manager, how data queries were handled and how data were to be processed at the end of the trial.

The trial monitoring plan described procedures for central monitoring and stated that no site monitoring would take place unless triggered by concerns. All recruitment centres were monitored centrally and none generated concerns sufficient to merit a monitoring visit.

Trial promotion