Through knee Amputations impact on Quality of Life compared to Above Knee Amputations - The HAMLET Trial

Research question: Does a through knee amputation (TKA) confer a quality of life (QoL) advantage over an above knee amputation (AKA) for patients requiring a major lower limb amputation (MLLA) but unsuitable for below knee amputation (BKA)?

Background: Almost half of MLLA in the UK are performed higher than a BKA level with the majority of these being performed as AKA procedures. A Cochrane review undertaken by the applicants identified no existing randomised data to determine comparative clinical or rehabilitation outcomes or complication rates of TKA and AKA. Current literature and expert opinion suggests that there may be a functional benefit to the longer residual limb resulting from a TKA but there is no robust evidence at present to support the choice of one level of amputation over another.

Recent registry analysis publications have suggested similar surgical outcomes and potential for improved rehabilitation and resultant QoL.

Aim: To compare the clinical and cost-effectiveness of TKA to that of AKA in patients requiring MLLA but who are unsuitable for BKA.

Methods A multicentre, two-arm, non-blinded, pragmatic randomised controlled superiority trial with parallel groups of adults requiring a MLLA for any reason who are not suitable for BKA. Randomisation will allocate 386 participants on a 1:1 ratio, stratified by indication (traumatic vs non traumatic), frailty, sex and presence of contralateral existing amputation, to either control (AKA) or intervention (TKA) arms.

There will be an internal pilot in 12 sites with strict progression criteria pertaining to recruitment and follow up rates.

Outcomes are selected to include; those prioritised by our PPI panel, the core outcome set for amputations, and alignment with the commissioned call briefing. Quality of Life (QoL) will be the primary outcome, measured using the EQ5D–5L preoperatively and at 4 monthly time points up to 2-years as per PPI members’ suggestion.

Secondary outcomes include qualitative, surgical and rehabilitation outcomes as well as longer term social and functional outcomes (to 24 months post procedure). Cost effectiveness will be determined using QALYs derived using the EQ-5D-5L. PROJECT TIMETABLE: Proposed June 2024 start: (Months) 0-9: Study set up, contracts, regulatory approvals

9-21: Pilot site set-up and recruitment 21: conclude pilot – Stop/Go analysis of feasibility 22: Main trial set up, 45: Complete recruitment 69: Last patient last follow up 69-75: Data cleaning, analysis and report

Anticipated impact and dissemination: The HAMLET trial will provide the first robust evidence to guide practice in selection of amputation level for patients who are unsuitable for a BKA. Impact and implementation should be swift as a training “blueprint” will be developed during trial site setup which can be used to rapidly implement TKA in UK centres if proven effective.

We anticipate multimodal results dissemination: UK vascular teams will be informed of results via the Vascular society amputation specialist interest group, publications in peer reviewed journals and conference presentations and via vascular research social media channels. Patient facing results dissemination will be via amputation charities, social media and the national press. Results would be expected to directly impact national and international guidelines on MLLA.