Manual Arthroplasty Versus VELYS Robotic-Assisted Solution Functional Alignment Arthroplasty for Knee Osteoarthritis

This multicentre, pragmatic, parallel-group, blinded RCT will compare VELYS robot-assisted functional alignment with conventional total knee arthroplasty. The trial will employ a clearly defined, reproducible surgical protocol that will incorporate evaluation of the study cohort using: established clinical and patient-reported outcome measures (PROMs); gold-standard three-dimensional (3D) motion analysis to objectively evaluate functional outcomes; detailed examination of intraoperative knee kinematics, pre-/post-operative hip-knee-ankle radiographic data, and healthcare system effects including economic, efficiency, and human factor measures.

Objectives

The primary objective is to compare knee-specific health outcomes in patients undergoing TKA performed with VELYS robot-assisted (raTKA) using functional alignment versus TKA performed manually (mTKA) using conventional instrumentation. The primary outcome measure will be differences between the two intervention groups (using an intention-to-treat approach) with regard to change in Forgotten Joint Score (FJS) preoperatively versus 6 months post-surgery. The secondary objectives are to:

1. Compare PROMs (FJS, EQ-5D-5L, Oxford Knee Score \[OKS\], satisfaction \[numeric rating scale; NRS\], 4-part Likert scale\], pain \[101-point scale VAS\]) at 6 weeks, 6 months, and 12 months; 2. Correlate these outcomes with radiographic alignment and intra-operative data; 3. Evaluate biomechanical outcomes using motion analysis laboratory assessment; 4. Functional and activity-related outcomes; 5. Evaluate the economic and efficiency effects of imageless raTKA relative to mTKA; 6. Evaluate the human factor effects of introducing a new RAS into healthcare teams; 7. Assess surgical safety and the incidence of adverse events in both groups.

Null hypothesis The null hypothesis is that functionally aligned raTKA using the VELYS imageless system does not result in a greater early improvement in knee-specific outcomes, as measured by change in Forgotten Joint Score at 6 months, compared with conventional mTKA.

Study design The study is designed as a multicentre, pragmatic, parallel-group blinded RCT. There are nested modular study components, including: an internal pilot to determine safety and practicability; a motion analysis evaluation, and a task load, efficiency, and clinician perspective evaluation. The lead centre for the study will be the Golden Jubilee University National Hospital (GJUNH). Additional centres will be based in the United Kingdom and Irish regions. All participating surgeons are high-volume arthroplasty surgeons (performing \>100 knee arthroplasties annually) and have extensive experience with robot-assisted surgery.

Surgeons and training All participating surgeons are high-volume arthroplasty surgeons (performing \>100 knee arthroplasties annually) and have extensive experience with robot-assisted surgery.

To minimise any learning curve effects and variability between centres, all surgeons will have completed manufacturer-delivered training and credentialling using both the manual and robotic systems, and a minimum of 20 Attune TKA non-trial cases will have been completed by all surgeons (comprising at least 10 manual Attune and 10 VELYS-assisted cases) before they recruit trial participants. A subgroup analysis of TKA performed early versus late on the clinical experience will be performed as part of the interim pilot study to evaluate for differences in outcomes and adverse events, and a sensitivity analysis will be performed if indicated.

Sample size The sample size calculation is based on detecting a minimum clinically important difference (MCID) of 7 points in the FJS at six months post-operatively. This is informed by Alton et al (2025), and a standard deviation of 24 points, as reported in Clement et al., 2021. Using a one-sided alpha of 0.05 and a power of 80%, it was calculated that 147 participants per group would be required. To account for an anticipated 15% loss to follow-up, the final recruitment target is 173 participants per group, yielding a total study population of 346 participants.

Outcome data from the internal pilot (the first 100 study participants who have completed their 6-month follow-up) will be analysed. A blinded pooled estimate of the outcome variance will be computed and used in a pre-specified sample size re-estimation algorithm. The analysis team will remain blinded to treatment allocation; any sample size adjustments will be made according to the pre-specified rules to preserve type I error.

For the motion analysis sub-study, a sample size of 52 participants (26 in the raTKA and mTKA groups respectively) has been determined to provide sufficient power to detect expected differences in peak medial knee contact force compared with matched healthy controls.

Recruitment Participants will be identified through routine NHS orthopaedic outpatient clinics at the participating centres, in accordance with the eligibility criteria by the clinical team. Potentially eligible patients will be highlighted by the research team who will provide patient information relating to the study, with adequate time for consideration of the relevant materials and discussion with the clinical team before consent is sought. Participants will be randomised on a 1:1 basis to receive either: mTKA or raTKA. A separate consent form will be provided for the MAL sub-study.

Recruitment is planned to take place over 36 months, with each participant followed for 12 months post-operatively. Due to the use of the Attune Medial Stabilized (MS) polyethylene insert, long-term observation will be conducted for a minimum of 10 years to evaluate survivorship and cross-validated with national registry data.

Randomisation Participants will be randomised in a 1:1 ratio to receive either manual TKA or VELYS robot-assisted functional alignment TKA. Randomisation will be performed using a secure web-based system (Research Electronic Data Capture \[REDCap\], Vanderbilt University, USA) incorporating computer-generated permuted block randomisation, stratified by recruitment centre. Block sizes will be randomly varied and concealed to ensure allocation concealment. Following written informed consent and collection of baseline data, site research staff will enroll and randomise participants.

All participants will receive standard perioperative and postoperative care according to local institutional practice, including anaesthesia, thromboprophylaxis, analgesia, mobilisation, physiotherapy, and routine follow-up. Concomitant care considered part of usual care is permitted. No additional trial-specific co-interventions are mandated other than the allocated surgical approach and study assessments. Use of alternative robotic systems, non-protocolised experimental surgical technologies, or non-standard implants or constraint not anticipated by the protocol will not be permitted unless clinically required in the interests of patient safety. Any such deviations and the reasons for them will be documented. Participants will continue to receive standard NHS care following their involvement in the study. No additional or special post-trial care is required.

Blinding The study is a randomised controlled trial with patient and outcome assessor blinding. It is not possible to blind surgeons given the nature of the interventions. Non-surgical clinical staff (e.g. ward nurses and allied health professionals) will be blinded. Femoral and tibial tracker pins will be placed within the surgical incision, avoiding the need for accessory incisions in raTKA cases or sham incisions to aid blinding in mTKA cases. Documentation will be redacted appropriately to prevent inadvertent unblinding of clinicians. PROMs will be completed independently by participants. Radiographic assessments and biomechanical analyses will be performed by assessors who are blinded to treatment allocation. All study data will be anonymised and the study arm concealed before the conduct of data analysis. No unblinding procedures are planned.

Routine unblinding is not planned. Unblinding will be permitted only where knowledge of treatment allocation is considered necessary for urgent clinical management or participant safety. Any request for unblinding should be made by the treating clinician to the Chief Investigator or delegated medically qualified investigator. The reason for unblinding, the date, the person authorising it, and the person informed will be documented in the trial records. The Sponsor will be informed, and the event will be reviewed by the Trial Steering Committee. Wherever possible, unblinding of one participant will not result in unblinding of outcome assessors or the wider trial team.

Withdrawal of subjects

Participants have the right to withdraw from the trial at any point and for any reason, without providing an explanation. Withdrawal from the study will not affect their routine clinical care. The Principal Investigators (or delegate) may also withdraw participants from the study intervention if it is deemed in their best interest, including but not limited to: * Development of a medical condition making continuation inappropriate; * Adverse Events (AEs) or Serious Adverse Events (SAEs) that necessitate discontinuation; * Significant protocol violations that compromise study integrity or participant safety; * Participant request or non-compliance with study procedures.

Data collected up to the point of withdrawal will be retained and included in analyses, unless the participant specifically requests data removal in line with GDPR provisions. Participants who withdraw before randomisation or before any study procedures will be replaced to ensure an adequate sample size. Participants who withdraw after randomisation will not be routinely replaced, unless withdrawal rates threaten study power, in which case replacement will be considered. If withdrawal occurs due to an AE or SAE, appropriate medical care will be provided and relevant safety follow-up conducted until the event has resolved or stabilised. All such cases will be reported in accordance with regulatory requirements. Participants will be informed of these arrangements during the consent process, and all efforts will be made to minimise the burden of continued safety follow-up for those who withdraw from the intervention arm of the study.

Surgical technique A thigh tourniquet will be used for the full case until closure of the arthrotomy, and a medial parapatellar approach to the knee will be used in all cases. A cemented Attune prosthesis with medial stabilised (MS) polyethylene insert will be implanted in all patients. Perioperative care will be delivered in a standardised fashion in accordance with safe established practice and will not vary according to treatment arm.

Manual TKA Participants randomised to this group will undergo manual TKA performed with conventional jig-based instrumentation using cemented Attune Knee System components (Johnson \& Johnson MedTech) and a medial stabilised (MS) polyethylene insert. The aim will be to correct deformity towards a neutral limb alignment and achieve a TKA that is stable throughout the flexion-extension arc.

Extramedullary referencing will be used to align the proximal tibial resection perpendicular to the axis of the tibia. Intramedullary referencing will be used to align the distal femoral resection based on pre-operative planning and intra-operative assessment. Femoral axial alignment will be set initially at 3 degrees of external rotation relative to the posterior condylar axis, typically perpendicular to Whiteside's line, and adjusted based on the flexion gap and patellar tracking. Measured bone resections will be made using the standard cutting guides for the Attune TKA system.

VELYS robot-assisted functional alignment TKA Participants allocated to the raTKA group w

• Change in Forgotten Joint Score [Срок оценки: Measured pre-operatively, and at 6 weeks, and 12 months.]
• Absolute Forgotten Joint Score [Срок оценки: Measured at 6 weeks, 6 months, and 12 months.]
• Oxford Knee Score [Срок оценки: Measured pre-operatively, at 6 weeks, 6 months, and 12 months.]
• EQ-5D-5L [Срок оценки: Measured pre-operatively, at 6 weeks, 6 months, and 12 months.]
• Satisfaction Score (Likert) [Срок оценки: Measured at 6 weeks, 6 months, and 12 months.]
• Satisfaction (VAS) [Срок оценки: Measured at 6 weeks, 6 months, and 12 months.]
• Pain Score [Срок оценки: Measured at 6 weeks, 6 months, and 12 months.]
• Patient Reported Outcome Measure anchor questions (FJS) [Срок оценки: 6 months.]
• Patient Reported Outcome Measure anchor questions (OKS) [Срок оценки: 6 months]
• Radiographic Parameters (HKA) [Срок оценки: Measured pre-operatively and at 6 months.]
• Radiographic Parameters (Component Assessment) [Срок оценки: Measured pre-operatively and at 6 months.]
• Motion Analysis Study (KAM) [Срок оценки: Motion analysis will take place pre-operatively and at 6 months.]