In the UK, around 5,000 major lower limb amputations (MLLA) occur every year, meaning that every 2 hours, someone in the UK has a leg removed and their life is changed forever. This number is increasing due to the ageing population and rising prevalence of diabetes. The care of these patients costs the NHS approximately £200 million a year, not including costs associated with formal and informal care, homecare visits and residential or nursing home placement. Following MLLA many patients do not return to independent living, with approximately one third being discharged to a care facility. MLLA also leads to substantial health implications, including anxiety, depression, altered body image and social discomfort, and the loss of general fitness and independence, which all contribute further to patient burden and healthcare costs.
MLLA includes below knee amputations (BKA), above knee amputations (AKA) and through knee amputations (TKA). Irrespective of the level of amputation, a MLLA has a significant impact on quality of life, though this can be mitigated. A recent review found that the ability to walk successfully with a prosthetic limb following MLLA, something more difficult with an AKA, had the greatest positive impact on quality of life. Accordingly, a BKA to preserve the knee joint, and thus maximise potential to utilise a prosthesis, is performed in preference to higher levels of amputation wherever possible. Patients not suitable for a BKA are usually offered an AKA, and less commonly a TKA as an alternative. Compared to an AKA, a TKA may result in superior outcomes via improved rehabilitation, easier control of an artificial leg and/or balance in a wheelchair. However, a TKA can also result in wound healing complications. Patients report positive and negative experiences with both AKA and TKA.
Why is the HAMLET Trial important?
When a BKA is not suitable, both AKA and TKA surgeries are used in clinical practice. TKA is rarely used in the UK (less than 2% of MLLA) though may confer benefits as above, however, high-quality research to provide evidence to clearly define which amputation method results in the best outcomes for patients is lacking.
Current guidelines reflect this lack of evidence and support the need for further research in this area. This need for further research is also supported by patients, carers, and healthcare professionals; a James Lind Alliance priority setting process ranked improving clinical outcomes for patients following MLLA as the third highest research priority.
A high quality randomised controlled trial is therefore needed to establish comprehensive, robust evidence for the clinical and cost effectiveness comparing TKA to AKA. This will greatly assist teams working with patients requiring a MLLA to decide upon the level of amputation that will confer the greatest advantage and the lowest risk of complications.
What will the HAMLET Trial achieve?
The HAMLET Trial will compare quality of life and rehabilitation outcomes as well as complications, and costs to the NHS following AKA or TKA. The trial will also assess patients lived experiences and acceptability of each amputation option.
A survey of UK vascular units indicated that TKA was performed in 78% of centres, though not all surgeons performed this procedure. The main barrier was a lack of evidence for its benefit. If the HAMLET trial finds that TKA is a more effective amputation option, then we will also explore how TKA can be implemented into clinical practice.
The results will help clinical teams to make more informed treatment decisions for patients needing a MLLA and this will lead to improved quality of life for these patients
Trial design
A multi-centre, two-arm, non-blinded, pragmatic, parallel group randomised controlled superiority trial.
Eligible patients who are not suitable for BKA and agree to join HAMLET will be randomised to have an AKA or a TKA procedure.
The trial started recruiting in April 2025 and recruitment will run for three years. Participants will be followed up remotely every four months, at 4, 8, 12, 16, 20 and 24-months post randomisation. This will allow for the comparison of the impact of the amputation level on quality of life, wound healing, re-operations, rehabilitation, walking ability, and costs to the NHS.
Semi-structured interviews will be conducted to include study participants, those who withdraw from the study and patients who decline to participate. The findings of these interviews will be used to understand the acceptability of the intervention and trial processes and inform aspects of trial design and delivery. These interviews will take place 8-10 weeks post-treatment.
To understand the longer-term impact of TKA and AKA on patient’s lives and recovery, as part of the qualitative study, we will follow up a subgroup of 20-24 patients for up to 3 years, with interviews at 12, 24 and 36 months post-operatively.
How to get involved?
The HAMLET team is keen to hear from new sites who wish to take part in this important trial. This includes both sites who routinely undertake AKA and TKA procedures
and
those that don’t routinely use TKA.
Where sites do not currently undertake TKA, we are able to offer training and support to surgical, rehab and prosthetics teams. We are currently scheduling our first surgical training session, with spaces still available, so now is an excellent time to engage with us!
Please get in touch and express your interest: ytu-hamlet-trial@york.ac.uk or 01904 321116
For further information visit: https://www.york.ac.uk/healthsciences/research/trials/ytutrialsandstudies/trials/hamlet/
The HAMLET trial protocol is available at: https://fundingawards.nihr.ac.uk/award/NIHR157343
.png)
.jpg){kind=logo}
