Traditional Versus Alternative Alignment in TKR
Traditional Versus Alternative Alignment in TKR
As many as 20% of patients are unhappy with the results of total knee replacement (TKR).
 Various changes to surgical technique have tried to address this but have not led to a
 significant improvement in the numbers of patients satisfied with their operation.

 Recently, attention has focussed on alignment of the leg. When viewed from the front, a
 number of people do not start with a straight, mechanically aligned leg. Traditionally, when
 implanting a knee replacement, the surgeon tries to put the shin bone half of the knee
 replacement perpendicular to the floor to equalise stresses on the in and outside of the
 joint. However, this may result in the alignment of the leg changing considerably, straining
 the soft tissues around the knee and contributing to dissatisfaction with TKR.

 There has been a move by some surgeons to change practice, and to implant the TKR in a way
 that replicates the alignment of the patient's own original knee- alternative alignment.
 Studies looking at alternative alignment have not shown any loss of satisfaction with results
 of TKR and indeed are showing some signs that in the short term, function of the knee may be
 better with the new technique.

 The research team are planning to run a study comparing the knee replacement used in Exeter-
 the Triathlon- when put in place using traditional alignment versus using the alternative
 alignment methods. The outcomes will be assessed in various ways including patient
 satisfaction questionnaires, measuring muscle strength, flexibility around the knee, and by
 assessments of alignment of the new knee on X-rays and Computerised Tomography scans. The
 research team will look at short term results for satisfaction and function of the knee, and
 in the long term look at wear and survivorship to see if patient satisfaction with TKR can be
 improved.
Research Question:

 When performing total knee replacement (TKR), does the use of the alternative alignment
 method result in improved function by comparison to a group undergoing the same procedure but
 using traditional technique? Primary Aim: To identify if the group undergoing TKR using
 alternative alignment method have a significantly improved functional outcome at 1 year when
 assessed by the Minimal Clinically Important Difference (MCID) of at least 5 points in the
 Oxford Knee Score (OKS) by comparison to the group using traditional alignment technique.

 Secondary Aims: To identify if the use of alternative alignment method when performing TKR
 results in:

 -  Shortened length of stay (LOS) in hospital

 -  Improved short term function when assessed by peak quadriceps or hamstrings muscle
 torque measured by myometer

 -  Lower hospital costs as a result of reduced LOS or operating time

 -  Enhanced improvement in patient outcome scores Knee Osteo-arthritis Outcome Score
 (KOOS), Oxford Knee Score (OKS), Euroquol (EQ5D) at short, mid and long term timeframes

 -  Enhanced positioning of the implants as assessed by a Computerised Tomography (CT) scan
 rotational profile assessment

 -  Enhanced range of knee flexion

 -  Any significant differences in component positioning, limb alignment or component wear

 -  Any significant changes in functional ability as measured by the Exeter Functional Lab
 protocol or Nurture activity assessment tool or the Instride Accelerometer by comparison
 to the TKR performed with traditional instruments.

 The research team will achieve these aims:

 -  By enrolling 126 patients into this study over a period of 2 years

 -  By carrying out a prospective randomised study looking at the subject matter over a
 period of 8 years

 -  By analysing patients functional status pre and post-surgery using patient generated
 questionnaires and data from the Exeter functional lab

 -  By analysing patients the 1 year radiological results from the plain x-rays to look at
 limb alignment, component position and wear

 -  By analysing the TKR component position on the pre and post-operative Computerised
 Tomography (CT) scans

 -  By collecting length of stay data taken from the patient administration system

 -  By collating all of the data from the study into a spread sheet for analysis by a
 professional statistician

 Scientific Background:

 Despite being one of the most successful of orthopaedic operations, a number of patients
 remain dissatisfied after TKR surgery. In a study of 253 patients, 1 year after TKR, Noble et
 al reported 11% of patients were neutral in their satisfaction after their surgery and 14%
 reported that they were either dissatisfied (3%) or very dissatisfied (11%). Reasons for this
 are not always clear.

 Various changes to surgical technique have tried to address this over the years. These
 include computer assisted navigation and patient specific knee replacement parts. However, to
 Brin et al, the clinical significance of this remains to be proven.

 More recently, attention has focussed on the alignment of the leg. Classic mechanical
 alignment (MA) in TKR is meant to co-align the prosthetic components to the mechanical axes
 of the femur and tibia and restore neutral overall limb alignment. Traditionally, surgeons
 have believed that implant durability is maximized when postoperative limb alignment is
 corrected to 0 ± 3 degrees relative to the mechanical axis. When implanting the tibial
 component of a TKR, the surgeon will try and put the device perpendicular to the tibial
 mechanical axis. This is done make sure the stresses on the new knee are equally placed on
 either side of the joint to try and prevent asymmetrical or accelerated wear on one side of
 the prosthesis. However, Bellemans et al examined 250 asymptomatic volunteers and identified
 that 32% of men and 17% of women have a varus deformity of the knee. Therefore, for many
 people, placement of the tibial component perpendicular to the tibial mechanical axis may
 result in the alignment of the leg changing considerably, putting new strains on the soft
 tissues around the knee itself as well as altering the biomechanics of the adjacent ankle and
 hip joints with the potential to generate soft tissue strain in these areas also. It is
 possible that this alignment change is a major contributing factor to the dissatisfaction of
 some patients with TKR.

 Concerns that a failure to achieve "correct" positioning of the TKR components may adversely
 affect the survivorship of the artificial joint may not be well founded. Bonner et al
 reported upon the survivorship 501 TKRs after 15 years of follow up. 396 implants were within
 3° of the mechanical axis and 105 were not. Whilst this latter group may have been expected
 to have performed inferiorly, the results showed no statistically significant difference in
 the survivorship of the 2 groups when revision for aseptic loosening was used as the end
 point for the analysis. Similarly, Parratte et al reviewed 398 TKR cases in whom 292 had
 post-operative limb alignment within 0-3° of the mechanical axis and 106 were outside of
 this. The authors concluded that a postoperative mechanical axis of 0° ± 3° did not improve
 the fifteen-year implant survival rate.

 Surgeons such as Waterson et al are therefore now questioning the old philosophy of
 alignment. There has been a move to change surgical practice and put the knee replacement
 parts in place in a way that replicates the alignment of the patient's own original
 knee-natural, alternative or kinematic alignment (KA). Importantly, several studies looking
 at this KA have not shown any loss of satisfaction with results of knee replacement, and show
 some signs that in the short term, function of the knee may be better with the new technique.

 Waterson et al reported 1 year follow up data in 71 patients undergoing TKR randomised to
 either KA (n = 36) or MA (n = 35). No significant differences were found between them in
 function one year post-operatively. The authors recommended further research is required to
 see if any theoretical long-term functional benefits of KA are realised or if there are any
 potential effects on implant survival. Interestingly, in this work, there was a greater
 improvement in the mean American Knee Society Score (AKSS) in the KA group at six weeks when
 compared with the MA group (p = 0.05). The measurements of peak torque in the quadriceps were
 also significantly better in the KA group at six weeks and three months (p = 0.003 and p =
 0.02 respectively) by comparison to the MA group. Whilst this randomised control trial failed
 to demonstrate any discernible difference between TKRs implanted in KA or MA at 1 year, the
 authors recommended mid- to longer-term follow-up to confirm the equivocal functional outcome
 and that survival of the TKR is not compromised by KA relative to MA. This new study takes
 this concept further using manual instruments to try and achieve KA.

 Mizner et al reported deficits in quadriceps force of 30-40% in patients for up to a year
 after TKR by comparison to age matched subjects. They describe reduction of quadriceps muscle
 performance has been correlated with fall risk, walking speed, speed and quality of
 sit-to-stand transfers, and performance during stair climbing in individuals older than 60
 years of age. Such functional deficits can impact significantly on quality of life and this
 functional reduction could be a contributory factor to the dissatisfaction with TKR reported
 by some patients. Bade et al identified similar reductions in quadriceps strength after TKR
 at 1 and 3 months post-op that took 6 months to recover to pre-operative levels. Again, this
 can have implications for functional recovery and satisfaction. If Waterson's work on KA
 versus MA shows improvements in early quadriceps function, then it is important to see if
 this can be progressed further and translated into improved function and satisfaction after
 TKR.

 Dossett et al reported the results of their work and evaluated an alternative alignment
 method (KA with patient-specific cutting guides) compared to the alignment results with MA
 with conventional instruments. This was a randomized controlled trial of 41 KA and 41 MA
 patients. In this work, the authors point out that because a mechanically aligned TKR strives
 to correct limb alignment to a straight line, the kinematics of the knee can be altered. They
 outline the principle behind KA i.e. placement of the components so that the orthogonal 3-D
 orientation of the 3 axes that describe normal knee kinematics is restored to that of the
 pre-arthritic knee. Two of their secondary outcome measures showed results in favour of the
 KA knee: The Oxford Score (OKS-0 is best and 48 worst) was 8 in the KA group and 15 in the MA
 group, a difference of 7 points, which was significant (P.001). The range of knee flexion was
 120° in the kinematically aligned group and 115° in the MA group, a difference of 5°, which
 was significant (P .043).

 It was also of interest that in the Dossett paper the operative time in the kinematically
 aligned group was 21 minutes less than the mechanically aligned group (P<000).

 In the short term at least, it would appear that KA of TKR components has the potential to
 deliver improvements in patient generated outcomes, quadriceps torque and flexibility of the
 knee which in theory could increase the number of patients satisfied with TKR. Concern about
 longer term failure of TKR if MA is not rigorously pursued appears to have been allayed.

 A study examining short, medium and longer term outcomes of KA, with a contemporary TKR
 design is needed to see if outcomes for patients scan be improved. This study has the
 potential to be of great importance in contributing to this question. Limb alignment has
 focussed on the need to achieve the zero degree goal of hip, knee and ankle alignment. To
 achieve real 3 dimensional (3D) more natural alignment, surgeons have to accept this goal may
 not be correct. There is a need to achieve pre-arthritic/pre-morbid alignment and to evaluate
 if this can unlock the potential for improved patient outcomes. A prospective, randomised
 study with multiple outcome measures can deliver a major contribution to the knowledge base
 of this subject and influence surgical practice with the aim of improving patient outcomes
 and satisfaction.

 Methodology:

 This study will be carried out at a single centre: The Exeter Knee Reconstruction Unit (EKRU)
 at the Royal Devon and Exeter (RD+E) Hospital. Different parts of the study will be carried
 out in the operating theatres, orthopaedic out-patients department and the physiotherapy
 department.

 Participant Selection:

 Study participants will be undergoing TKR under the care of the EKRU at the RD+E Hospital.

 Patients will be identified as potential participants in 1 of 2 ways. Firstly, by their
 surgeon when they are listed for TKR surgery. The surgeon will outline the study, provide the
 patient with the study patient information leaflet and a copy of the study consent form and
 ask permission from the patient to allow one of the research team to contact them.
 Alternatively, they will be identified from the current surgical waiting list as suitable for
 inclusion. In this latter case, their surgeon will write to the patient requesting permission
 for one of the research team to contact them by telephone to discuss the study and to enquire
 if the patient would enrol. A patient information leaflet about the study will accompany this
 letter.

 The patient will have an opportunity to provisionally agree or decline enrolment during this
 telephone call.

 Written consent for participation will be obtained on a study specific Ethics Committee
 approved consent form on attendance at the hospital for the pre-operative CT scan. The
 pre-operative data will be collected including: demographics and medical history, Knee
 Osteo-arthritis Outcome Score (KOOS), Oxford Knee Score (OKS), the Euroquol 5 Dimension
 Questionnaire (EQ5D) score, the Forgotten Knee Score (FKS) and the Knee Society Score (KSS),
 the SF36, the University of California at Los Angeles (UCLA) activity score, pain
 measurements by Visual Analogue Scale (VAS) during rest and activity and detail of the use of
 pain medication. The research team member will assess participants overall joint flexibility
 using the Beighton scale. An assessment of pre-operative anxiety and depression will be made
 via the Hospital Anxiety and Depression Scale (HADS) 3 copies of written consent will be
 obtained- one original and 2 photocopies. The original will be kept by the research team in
 the study masterfile, one will be returned to the patient and one will be placed in the
 medical notes.

 Routine care for these patients from their clinic appointment includes X-ray of the affected
 knee, full leg alignment X-ray, and an assessment of their active and passive range of motion
 of the knee.

 All information collected pre-operatively will be used to quantify the sample population and
 compare post-operative progression.

 Pre-operative Radiological Assessment:

 In addition to routine care, all study participants will undergo 1) a pre-operative CT scan
 of the affected leg (spiral CT through the hip, knee and ankle) and 2) a whole leg
 antero-posterior (AP) radiograph standing on one leg (the leg about to have a TKR and
 involved in the study) and 3) a lateral "heel-hang" X-ray of the knee for surgery.

 Pre-operative Functional Assessment:

 Study participants will attend the Functional Lab in the physiotherapy department at the RD+E
 Hospital for an assessment of their functional ability using the Exeter Functional lab
 protocol and the Nurture and Instride devices.

 Randomisation:

 This will be a randomised, prospective, blinded study with 2 arms of 63 patients each. Arm 1
 will receive a Triathlon TKR implanted using the traditional/MA method and arm 2 will receive
 a Triathlon TKR using the KA/alternative alignment method. The randomization schedule will be
 determined using an on-line random assignment sequence generator
 (www.graphpad.com/quickcalcs/randomize1.cfm), kept and controlled by the study co-ordinator.
 Randomisation assignment will be transcribed onto paper, and placed inside a sealed opaque
 envelope.

 Any deviation from the assigned treatment group by a surgeon will be reported as a deviation
 from protocol and the case will be terminated from the study.

 Sample Size:

 126 patients (63 per arm). The sample size was determined using the primary outcome measure,
 OKS measured at 12-month follow-up, which has a Minimal Clinically Important Difference
 (MCID) of 5 units (Clement et al). To detect a between group mean difference of 5 units, with
 90% power and significance threshold of 0.05, using a standard deviation in both groups of
 7.6 (Clement et al), requires 50 participants per group. Assuming 20% attrition, 63
 participants per group are required.

 Admission to Hospital for Surgery and Hospital Stay: will occur in the routine way as for all
 patients undergoing TKR in this hospital.

 All surgeries will be carried out using the MAKO robotic arm system to ensure accurate bony
 cuts and implant placement is achieved.

 Post-operative Follow Up:

 -  Participants will be reviewed at 6 weeks, 3 and 6 months, 1, 2 and 5 years
 post-operatively. (3 and 6 month appointments in addition to routine care).

 -  The 6 post-operative visits for functional testing are in addition to routine care.

 -  The study will terminate at 5 years after which patients will return to the usual
 post-operative management schedule of a further review 10 years post-operatively.

 Post-operative Radiological Assessment:

 -  Participants will undergo X-ray examination of the knee post-operatively whilst in
 hospital and then at 1, 2 and 5 years- as per routine care

 -  Participants will undergo one post-op spiral CT scan examination of the affected leg at
 approximately 6 weeks after surgery (spiral CT through hip, knee and ankle) and a repeat
 of the whole leg AP radiograph standing on one leg (the leg that has just had a TKR and
 is involved in the study) at 1 year post-operatively. This is in addition to routine
 care.

 Surgery:

 Operating techniques will be standard techniques as used by the 4 experienced TKR surgeons
 involved in the study with the exception of the alignment of the components which will be
 decided upon in the randomisation schedule for use of the traditional MA or the KA method.

 The use of the MAKO robotic arm system will be in all cases. All components will be cemented
 in situ using the Triathlon Cruciate Retaining (CR) Implant with an X3 polyethylene insert.

 All patellae will be resurfaced. After surgery, patients will be discharged home allowed to
 fully weight-bear as comfort allows and with walking aids for use for a 6 week period if
 required. All patients will be instructed in an exercise regime whilst in hospital which they
 will continue after discharge and post-operative out-patient physiotherapy will be provided
 on an as needed basis- treatment type and frequency will be decided upon by the individual
 physiotherapist seeing each patient reflectinfg the care given to TKR patients in the region.

 Study Blinding:

 The following people will be blinded as to which arm of the study the patient is allocated
 to:

 -  The patient

 -  The functional assessor in the physiotherapy department

 -  The physiotherapist providing post-operative physiotherapy

 -  The radiologist reporting the CT scans

 -  The 2 surgeons reporting the X-ray findings-no surgeon will report on his or her own
 patients

 Data Collation:

 To be undertaken by the clinician undertaking the specific procedure concerned. The research
 coordinator or the research nurses attached to the RD+E Hospital R+D department will collect
 the pre-op consent, the pre and post-op Patient recorded Outcome Measures (PROMs). Data will
 be entered on to the study database by them the accuracy of entry double checked by them i.e.
 one person enters the data and a second checks its accuracy.

 RD+E Hospital physiotherapists will be responsible for collection of the Functional
 Assessment data.

 The 4 surgeons will be responsible for clinic data and communications, operation note
 details, reporting on X-ray findings- all of these to be on the hospital Clinical
 Documentation Management (CDM) system.

 Dr Anaspure will report the CT scan findings. All data will be stored on RD+E NHSFT secure
 computers. Data will be entered into an Excel spreadsheet for later transfer into a
 statistical package such as Statistical Package for the Social Sciences (SPSS) version 24,
 for analysis. All patient identifiers will be removed. At the end of the study, when all
 analysis of the data has been completed, the study data will be archived as per the sponsor's
 archiving Standard Operating Procedures (SOP).

 Statistical analysis. The research team will arrange for independent statistical analysis of
 the results by Dr. Fiona Warren from the University of Exeter Clinical Trials Unit (CTU).

 All outcomes will be reported descriptively by group, with continuous outcomes reported as
 mean (standard deviation) or median (interquartile range).

 All continuous outcome measures, including the primary outcome (OKS) will be analysed using
 linear regression modelling with adjustment for randomisation variables (surgeon, severity
 based on baseline OKS, and age (below 70, 70 and above), and baseline measurement. EQ5D will
 be analysed using the equivalent analyses with Tobit regression. Between group comparisons
 will be reported using confidence intervals and p-values.

 For continuous measures recorded at multiple time points, hierarchical regression models will
 be used to assess the interaction between intervention and timepoint, with the interaction
 effect reported as a global p-value.

 All analyses will be reported using the intention to treat principle. The primary analyses
 will include complete case data only. The amount of missing data will be reported for all
 outcome variables. In the event of substantive missing data (more than 5%), a secondary
 analysis will be performed including observed data and missing data imputed using multiple
 chained equations.

 Timescale:

 EKRU carry out 25 TKR procedures per month. The research team understand that studies have,
 on average, 54% of potential participants who choose not to be part of the research and
 believe it is reasonable to recruit 11 cases per month. However, will be allowed to achieve
 the sample size of 126 in case recruitment is slower than anticipated.

 Each patient will remain part of the study for approximately 5 years. Total duration of the
 study will be 8 years. (2 years to recruit participants, 5 years of follow up and data
 collection and one further year for data collation, cleansing and evaluation, statistical
 analysis and writing up of the study findings).

 Dissemination of Results:

 Participants will be informed in writing of the results if they so desire. The (R+D) Office
 at the RD+E Hospital will be informed of the results.

 The results of this research will be presented both nationally and internationally at knee
 surgery conferences, and published in a peer reviewed journal.

 Impact of Research:

 Unknown. If the research identifies a clear advantage of one study arm over the others, then
 it is likely that this technique will become standard TKR procedure in the EKRU- with the aim
 of providing patients with the best clinical and functional results after TKR surgery.
 Similarly, if a clear difference is found in one study arm, one would hope that presentation
 of the results to colleagues at other institutions will result in better long term results
 for their patients.

 In the event that no technique proves superior to the others, then this will provide surgeons
 with the reassurance that no matter what their preferred technique, their patient is not
 being disadvantaged.

 If one arm of the study out performs the other in clinical and functional results, there may
 also be cost differences between the arms of the study which could result in cost savings for
 the NHS.

 Costs:

 The EKRU has signed a Masters Service Agreement with Stryker UK to support its research
 projects. The study will remain an investigator initiated one, independent of influence of
 Stryker. As such all anticipated costs of the study will be covered.

 Measures to avoid bias:

 -  The patients will be blinded as to which arm of the study they are allocated to.

 -  The operating surgeon cannot be blinded to randomisation as he will be performing the
 surgery.

 -  The member of staff interpreting the results of the CT scan (Dr Anaspure) will be
 blinded as to which group the patients are allocated to

 -  The physiotherapist carrying out the functional assessments will be blinded to study arm
 allocation as will the physiotherapists carrying out post-operative out-patient
 rehabilitation

 -  No surgeon will report upon the x-rays of a patient upon whom he/she operated

 -  The statistician analysing the results will be blinded to study arm allocation

 Patient involvement:

 The study research team have consulted with patients on the feasibility of participating in
 the study at all and in particular about the demands of attending the appointments for
 functional assessment and CT scans. The study was discussed at the EKRU patient research
 panel. (This panel is a group of patients who have undergone knee replacement surgery in this
 Unit and who are therefore, well placed to comment on the practicalities of study
 involvement, as well as on the appropriateness and clarity of the patient information
 leaflet.) Attendance at all time frames is critical for completion of the secondary measure
 functional outcome and it was stressed by the patient representatives that the patients need
 to be fully informed of the commitment required should they agree to take part. Similarly, it
 was recommended that the extra commitment for CT scan appointments be highlighted.

 Bi-annual meetings of the patient research panel are held and if issues arise when running
 the study that require further patient involvement, they will be taken them to the panel for
 consultation. If a meeting is not due for some time, a panel member will be contacted
 personally for their advice. When the research team consulted on the design and wording of
 the patient information leaflet and the consent form, various changes were recommended and
 implemented.

 Risks/Monitoring Adverse Events/Stopping the Study:

 A log of adverse events, serious adverse events, adverse device effects and serious adverse
 device effects will be kept by the study coordinator. Any such event events occurring in the
 immediate peri and post-operative events should be reported to the coordinator by the
 consultant surgeon in charge of the case who will contact the study sponsor within the time
 frames as specified by them. Similarly any such adverse events may be identified in clinic
 and again, the surgeon concerned should report these back to the coordinator to be logged and
 the sponsor will be informed.

 It is possible that adverse events will occur that are dealt with either by the Accident and
 Emergency (A+E) department, the patient's General Practitioner (GP) or other hospitals. These
 may not be readily apparent to the research team. The operating surgeon will specifically ask
 participants to inform the research team if any complications or adverse events occur at each
 clinic attendance.

 A meeting of the research team will be held on a 3 monthly basis to discuss progress of the
 study, any specific problems and to consider whether there are any justifications for
 stopping the study. As both techniques being studied of performing TKR are already in use, it
 is not anticipated that there will be an unexpected complication that would necessitate an
 early termination of the study.

 Ethical considerations Ethical approval for this study will be sought from the National
 Research Ethics Service and the Health Research Authority.

 The study coordinator has discussed the study with the radiological protection officer at the
 RD+E Hospital who has provided radiation dose calculations as follows:

 All patients undergoing these total knee replacement operations in our hospital receive AP
 and Lateral radiographs of the knee on 5 occasions (pre & post op, at 1, 2 years and 5
 years), 2 AP radiographs of both legs at pre-op & 1 year. This is routine care. The total
 dose arising from these examinations is 81 millisiverts (µSv) as described by the Health
 Protection Agency Centre for Radiation, Chemicals and Environmental Hazards (HPA-CRCE) Report
 012, 2010.

 In addition, patients enrolled in this trial will require 2 additional whole leg AP x-rays, 1
 lateral x-ray of the knee and 2 CT scans covering the hip, knee and ankle. The total dose
 that a patient participating in this trial will receive is 1.7mSv, of which 1.6mSv is in
 addition to standard care.

 Participants are >/= 60 years of age and pregnant women are excluded from the trial.

 The lifetime risk of developing a cancer resulting from the total radiation dose is 1 in
 21,900 for a 60 year old patient; this would fall to 1 in 84,900 for an 80 year old patient.
 For the ages of the expected cohort, this is considered to be a very low risk (HPA-CRCE-028,
 2011 and NRPB, 2001) and is equivalent to around 8.5 months of natural background radiation
 in the UK.

 The lifetime risk of developing a cancer resulting from the excess dose in this trial is 1 in
 23,000 for a 60 year old patient; this would fall to 1 in 93,800for an 80 year old patient.
 For the ages of the expected cohort, this is considered to be a low risk (HPA-CRCE-028, 2011
 and NRPB, 2001) and is equivalent to around 8 months of natural background radiation in the
 UK.

 With participants consent, the research team will send anonymised data regarding the
 navigation findings during the operation, as well as CT and X-ray findings from pre-and
 post-surgery to Stryker UK. This will be with the purpose of providing information to allow
 the company to improve surgical technique, as well as implant and instrumentation design. No
 personal identifiers will be used when this information is sent to Stryker UK

 Conflicts of Interest:

 Stryker UK have supported this study financially. However, it remains completely independent
 from them in study design, results and dissemination of findings. The 4 operating surgeons
 all undertake consultancy work for Stryker UK and will complete the necessary applications
 regarding this on the ethics application for this study.

 Confidentiality All of the research staff are trained in the guidelines for Good Clinical
 Practice (GCP) in research. All National Health Service (NHS) staff involved are bound by
 patient confidentiality requirements of the NHS.

 The study participants GP will be informed that their patient is involved in the research-
 particularly as the patient may wish to discuss their involvement in the research with their
 GP.

 All of the data associated with the study will be kept electronically on the hard drives of
 computers within the Exeter Knee Reconstruction Unit (EKRU). It will be stored on encrypted
 and password protected hospital computers. The data will only be accessible by members of the
 research team and by the Research and Development (R+D) department at the RD+E Hospital who
 will require access to the data to ensure compliance with the protocol and that all study
 regulatory requirements are being met.

 When the data is sent for statistical analysis, all personal identifiers will be removed and
 a study number only used for identification.

 No personal identifiers will be used when information about the navigation findings, and CT
 scans and X-rays findings is sent to Stryker UK At the end of the study (see timescales
 above), all research data will be archived as per our sponsors archiving SOP. Radiographs and
 scans will remain on the secure hospital systems as per routine care.
Inclusion Criteria:• Patients undergoing primary TKR at the RD+E Hospital

 -  Patients must have completed a consent form for the study

 -  Patients must be prepared to comply with the pre and post-operative investigations,
 rehabilitation, attendance schedule and questionnaire schedule of the study

 -  Patient in whom any varus deformity present is <20°

 -  The diagnosis is of tricompartmental osteoarthritis of the knee

 -  Patient has primary diagnosis of Non-Inflammatory Degenerative Joint Disease (NIDJD).

 -  BMI<40

 -  Aged =/> 60 years at time of surgery

 Exclusion Criteria:• Refusal to consent to the study

 -  If the knee for surgery has a fixed flexion deformity ≥15°- this will be assessed by a
 lateral "heel-hang" x-ray of the knee for surgery

 -  If the knee for surgery has a varus deformity ≥20°

 -  If the knee for surgery has a valgus deformity i.e. hip/knee/ankle alignment angle <0°

 -  Pre-op Oxford Knee Score <8

 -  Pre-op knee flexion ability <90°

 -  If the natural posterior tibial slope measured is in excess of 10°

 -  Any patient whose post-operative recovery or ability to comply with the post-operative
 rehabilitation and assessment schedules is compromised by known existing other medical
 conditions

 -  Pregnancy

 -  Prisoners

 -  A patient known to have substance abuse or psychological disorders that could
 interfere with their ability to comply with the post-operative rehabilitation and
 assessment schedules

 -  Patients unable to read or understand the patient information leaflet and consent form

 -  Patient has a known sensitivity to device materials.

 -  Patient has a Body Mass Index (BMI) ≥ 40.

 -  Patient has an active or suspected latent infection in or about the affected knee
 joint at time of study device implantation.

 -  Patient has received any orthopaedic surgical intervention to the lower extremities
 within the past year or is expected to require any orthopaedic surgical intervention
 to the lower extremities, other than the TKR to be enrolled in this study, within the
 next year.

 -  Patient requires bilateral total knee replacements, or has a history of unsuccessful
 contralateral partial or total knee replacement.

 -  Patient has chronic heart failure (NYHA Stage ≥ 2)

 -  Patient has a neuromuscular or neurosensory deficiency, which limits the ability to
 evaluate the safety and efficacy of the device.

 -  Patient is diagnosed with a systemic disease (e.g. Lupus Erythematosus) or a metabolic
 disorder (e.g. Paget's disease) leading to progressive bone deterioration.

 -  Patient is immunologically suppressed or receiving steroids in excess of normal
 physiological requirements (e.g. > 30 days).

 -  Patient requires revision surgery of a previously implanted total knee replacement or
 knee fusion to the affected joint.