Prospective Randomized Controlled Trial of Functionally Aligned Robotically Assisted Total Knee Arthroplasty vs Patient Specific Custom Made Total Knee Arthroplasty
Phase: NA
Conditions: Knee Osteoarthritis
Sponsor: Austrian Workers Compensation Board Styria

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Prospective randomized controlled 
trial of functionally aligned 
robotically assisted total knee 
arthroplasty vs patient specific 
custom made total knee 
arthroplasty  
 
Short title: Knieathlon 
 
 
 
 
 
Principal investigator: Priv.-Doz. DDr. Antonio Klasan, EMBA 
 
 
 
 
 
 

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Background and rationale: 
 
Total knee arthroplasty (TKA) is an established treatment for patients with symptomatic 
endstage osteoarthritis. The aim of TKA is to provide pain relief and restore function; 
however, published literature identifies a consistent subset of patients who are not satisfied 
post-operatively1. There is a strong push away from what used to be the golden standard of 
TKA, mechanical alignment (MA)2. In brief, MA is a strategy of implant positioning that 
completely disregards any patient specific anatomy and orients the femoral and the tibial 
component parallel to the ground or perpendicular to the mechanical axis of the femur and 
the tibia, respectively2. In the sagittal plane, a similar approach is performed – the femoral 
component should be the smallest possible and the tibial component is always put at 3 
degrees to the floor. Finally, in the axial plane, the tibial component is oriented according to 
the axis between the attachment of the posterior cruciate ligament and the medial/mid third 
junction of the tibial tuberosity. As one can expect, a very recent paper lists 10 flaws of this 
approach2. This approach, due to its predictability and safety, remains the golden standard1.  
A strong and a safe transition towards more personalized alignment is advised3. This is 
achieved safely and effectively using robotic assisted surgery (RAS), such as the MAKO Surgical 
System (Stryker). The system is intraoperatively used to adjust the implant position according 
to the patient anatomy and the soft tissue structure for every given knee. This approach, 
labelled functional alignment (FA) is still very new and complicated as it requires excellent 
understanding of the anatomy and the surgical software, forcing the surgeon to perform 
significantly more decisions. For this procedure, the surgeon still uses a uniform design, off 
the shelf-implant that has been demonstrated to force the surgeon to compromise on the 
trochlear position due to the fixed rotation of the posterior femoral component and the 
trochlea orientation4. The results of this approach, however, do seem to bring improvements 
at 1 year compared to MA5. Currently, one study comparing this approach (FA) and the 
traditional approach (MA) is being compared in a blinded fashion, using RAS in both instances, 
in New Zealand 6.  
The huge downside of RAS for the healthcare providers are very high upfront costs and 
significant costs of disposables making the cost-effectiveness of RAS always a topic of debate 
with ongoing trials 7–9. One potential alternative that has no upfront costs and marginal 
increase in manufacturer costs is a custom-made, patient specific implant (CM-PSI). The tools 

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to deliver the implant, patient-specific instruments (PSI), are less precise than RAS, but the 
implant itself is completely customized to the patient’s anatomy and soft tissue envelope, 
without any compromise, even in the design of the trochlea. This results in a reported patient 
satisfaction of 94% at 2 years10.  
 
Currently there is no ongoing trial or a published planned trial comparing these two 
techniques in the world. To the authors’ best knowledge and information, such a study is also 
not planned due to a number of high preconditions that are needed for such a study.  
 
Objectives and hypothesis 
 
The primary objective of this study is to compare the Forgotten Joint Score (FJS) in RAS-FA 
TKA versus CM-PSI TKA at 2 years post-operatively. The FJS is a score that measures the 
restoration of ‘normal joint feeling’, and the hypothesis is that patients undergoing RAS-FA 
TKA will have a superior score.  
 
Secondary objectives include: 
- 
Clinical outcomes using the Kujala anterior knee pain Score. This questionnaire is 
designed to assess the anterior knee compartment. This has been included due to the 
difference in implant design that cannot be compensated for using robotics 
- 
Satisfaction after surgery (very dissatisfied-somewhat dissatisfied-neutral-satisfied-
very satisfied) 
- 
Pain scale using VAS 
- 
Surgical efficiency by comparing operative times and total theatre time  
- 
Comparison of opioid use 
- 
Number of physiotherapy sessions during hospital stay 
- 
Range of motion measurements 
- 
Radiographic data including radiolucent lines  
 
Methods 
The study will be conducted across the 2 sites of the AUVA UKH Steiermark Hospitals. All 
patients will have surgery, inpatient stays and follow-up at the sites.  

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Eligibility criteria 
Inclusion criteria: 
- 
The patient is a male or non-pregnant female between the ages of 40 and 90 years 
- 
The patient requires a primary total knee replacement 
- 
Patient is deemed appropriate for a cruciate retaining knee replacement 
- 
The patient has a primary diagnosis of osteoarthritis (OA) 
- 
The patient has intact collateral ligaments 
- 
The patient is able to undergo CT scanning of the affected limb 
- 
The patient has signed the study specific, ethics-approved, informed consent 
document 
- 
The patient is willing and able to comply with the specified pre-operative and post-
operative clinical and radiographic evaluations 
 
Exclusion criteria: 
- 
The patient has a history of total, unicompartmental reconstruction or fusion of the 
affected joint 
- 
Patient has had a previous osteotomy around the knee 
- 
The patient is morbidly obese (BMI > 41) 
- 
The patient has a deformity which will require the use of stems, wedges or augments 
- 
The patient has a varus deformity ≥ 15° 
- 
The patient has a valgus deformity >3° 
- 
The patient has a neuromuscular or neurosensory deficiency, which would limit the 
ability to assess the performance of the device  
- 
The patient is unable to speak German 
- 
The patient is pregnant 
 
For recruitment purposes, a special Knee arthroplasty clinic will be organized at the hospitals. 
All patients will be screened by the orthopaedic surgeon and research coordinator based on 
the criteria. Patients that meet these criteria and express an interest in participating will be 
provided an ethics approved patient information sheet following initial consultation with their 
treating doctor. This sheet provides more detail about the study, potential risks and 

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requirements for follow-up. Pre-operative visits include the collection of consent, CT scan, x-
rays and completion of patient reported outcomes. 
Interventions 
Both techniques have a demonstrated safety track record comparable to MA, and have data 
supporting increased outcomes when compared to MA. Their direct comparison is yet to be 
performed in an RCT.  
 
All patients will receive a CT scan of the leg, either the MAKO protocol11 or the Symbios 
protocol12.  
In case of RAS TKA, the CT is loaded onto the MAKO planning software, calibrated by a 
technician and the plan is approved by the surgeon prior to the study. The initial position of 
the implant is kinematic alignment (KA), aiming to restore the lost bone+cartilage using the 
implant. The position is then intraoperatively, prior to the cuts, modified by the surgeon to 
accommodate any differences caused by the soft tissue envelope. Research has 
demonstrated that an adjustment is performed in more than 90% of cases13. The primary goal 
of FA is to maintain the native joint line while achieving even soft tissue gaps in extension and 
medial flexion, while preserving the femoral orientation as much as possible (femoral 
preserving FA).  
In case of CM-PSI TKA, the CT scan is uploaded to the Symbios online Planning platform where 
a technician performs a “pre-plan”, adjusting the implant position to similar principles as for 
RAS TKA. However, the perfect balancing and positioning can be achieved by modifying the 
implant design. The design and the position is approved by the surgeon digitally, and the 
implant with the instruments in manufactured and shipped to the healthcare facility. This 
process requires 6 weeks.  
Both interventions are made via a central incision and medial parapatellar approach, patients 
receive a CT scan in both cases and the waiting list is longer than 6 weeks irrespective of the 
study, making the procedure blinded for the participant.  
 
As the intervention relates to surgical technique, all strategies are focused on patient 
management intraoperatively. All participants will continue standard post-operative care 
with their surgeon at their conclusion of the trial. All participants will undergo assessment by 
the research team pre-operatively, and at 6 weeks, 6 months, 12 months and 24 months post-

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operatively. The research team will assist in the randomisation process and cannot be blinded 
to the allocation. Physiotherapists will also record functional measures of recovery during in-
patient stay and will be blinded to the allocated alignment. Participants will be recruited from 
AUVA UKH Hospitals in Graz, Austria. The trial aims to recruit 10 patients per month, with the 
recruitment process estimated to take 12 months.  
 
Sample size 
This trial seeks to determine if robotic arm-assisted TKA following FA principles provides 
superior clinical outcomes to patient specific custom made TKA. Ingelsrud et al. reported that 
the minimal clinically important change in FJS for TKA patients was 14 points14 which has been 
used as the effect size for this study. Mean forgotten joint score in clinical trials at 2 years has 
been reported at 66 with a standard deviation of 2615. Using a power of 80% (β=0.2), 
significance level of 5% (α=0.05) and accounting for 10% loss to follow-up yields a sample size 
of 60 participants per arm. 
 
Randomization 
A master randomisation sequence will be generated prior to the start of the trial using an 
online random number generator (www.sealedenvelope.com). The master sequence will be 
maintained by the principal investigator and patients will be allocated a treatment in 
sequential order following consent.  
 
Blinding 
The participants, physiotherapists and assessors will be blinded to the treatment allocation. 
The participant identification list will be archived at the site on a secure network in a 
password-protected file, with the research team having access to the file. The investigators 
and research team are unable to be blinded to the allocation due to their role in the allocation 
of treatment and execution of surgery. Participants will be unblinded to the intervention at 
the end of the trial, unless there is a medical reason to do so prior to the end of the study. 
Due to the minimal requirement of 6 weeks to manufacture the custom-made implant, 
surgery will be performed not sooner than 6 weeks after booking of the case.  
 
Data collection 

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Outcomes will be primarily captured on paper, transferred to an excel table manually and 
stored using a password-protected electronic platform on the internal server of the 
healthcare facility.  
For the purposes of group comparisons, we will collect age, gender, BMI and ASA score. In 
order to compare radiologic osteoarthritis severity and knee phenotypes, we will classify all 
knees according to the Kellgren-Lawrence classification16 and the CPAK classification17.  
 
Preop 
In-
hospital 
stay 
6 weeks 
3 months 
6 months 
12 months 
24 months 
x-ray 
 
x-ray 
 
x-ray 
x-ray 
x-ray 
FJS 
 
FJS 
FJS 
FJS 
FJS 
FJS 
Kujala 
 
Kujala 
Kujala 
Kujala 
Kujala 
Kujala 
VAS 
 
VAS 
VAS 
VAS 
VAS 
VAS 
 
 
Satisfaction Satisfaction Satisfaction Satisfaction Satisfaction 
ROM 
 
ROM 
ROM 
ROM 
ROM 
ROM 
 
Times 
Opioids 
Physio 
 
 
 
 
 
Table 1 – Overview of timepoints for data collection 
 
 
Data management 
The International Council for Harmonisation guidelines for Good Clinical Practice (ICH GCP) 
will be followed throughout the study. The sponsor will conduct routine monitoring visits for 
data verification against source material, as defined by participant entered data or medical 
records. Data collected by the sponsor will be stored electronically in a password-protected 
folder with restricted user access. Periodic surgeon investigator meetings will also be held to 
review participants where treatment has deviated from the protocol. The chief investigator 
will be responsible for the training and sign- off of all staff working on the study. 
 

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Confidentiality 
All research staff and investigators will be employed by the AUVA and will comply with its 
confidentiality practices. All participants will be allocated a unique non-identifiable study 
number and any information disseminated in journals or conferences will ensure patient 
anonymity is maintained. 
 
Statistical methods 
The primary and secondary outcome data gathered from patients in each study group will be 
pooled and summarised. The mean, standard deviation and 95% confidence intervals will be 
calculated for each measure in each group. All outcome measures will be assessed on their 
distribution and homogeneity to confirm the appropriate statistical model. Adjustments will 
be made for multiple testing over time. Pairwise comparisons will be examined using a paired 
t-test if normally distributed or non-parametric test for skewed distribution. Categorical data 
will be evaluated using frequency and percent distributions, with significance testing per- 
formed using Fisher exact test or chi-squared test. Statistical significance is defined as a p-
value < 0.05. 
 
Data assessment 
Interim analysis will be conducted at milestones of 6-month and 1-year follow-up for 
dissemination of results. Periodic analysis will also be conducted for patient safety. Sub-group 
analysis based on patient phenotype will be dependent on sufficient post hoc sample size 
calculations. A per-protocol and intention to treat analysis will be performed. In the event of 
randomisation errors, the participant will be converted to the study arm that represents the 
received treatment. The statistical model will be corrected in the event of missing data and 
to avoid type I error when performing multiple comparisons. 
 
Oversight and monitoring 
The principal investigator will be responsible for execution of GCP, delegation of authority to 
research staff and will review adverse events and protocol deviations. The principal 
investigator will review all adverse event forms for safety assessment. Any device or 
treatment related adverse events will be reviewed regularly by the Investigator team and a 
midpoint assessment of patient report outcomes will be conducted. An adverse event (AE) is 

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defined as any undesirable clinical occurrence in a participant, whether it is considered to be 
device related or not, that includes a clinical sign, symptom or condition and/or an 
observation of an unintended technical performance or performance outcome of the device. 
A serious adverse event (SAE) is an adverse event that results in hospitalisation or 
prolongation of existing hospitalisation, persistent or significant disability or incapacity, life-
threatening or death. All will be reported to the principal investigator. All series adverse 
events will be periodically examined using an alert in the participants electronic medical 
records and will be reviewed periodically in-line with the evaluation schedule. 
 
 
 
 
Referenzen: 
 1.  Clement ND, Bardgett M, Weir D, Holland J, Gerrand C, Deehan DJ. Three groups of 
dissatisfied patients exist after total knee arthroplasty: early, persistent, and late. Bone 
Joint J. 2018 Feb;100-B(2):161–9.  
2.  Beckers G, Meneghini RM, Hirschmann MT, Kostretzis L, Kiss MO, Vendittoli PA. Ten 
Flaws of Systematic Mechanical Alignment Total Knee Arthroplasty. J Arthroplasty. 2023 
Nov 23;S0883-5403(23)01167-1.  
3.  von Eisenhart-Rothe R, Lustig S, Graichen H, Koch PP, Becker R, Mullaji A, et al. A safe 
transition to a more personalized alignment in total knee arthroplasty: the importance 
of a “safe zone” concept. Knee Surg Sports Traumatol Arthrosc. 2022 Feb;30(2):365–7.  
4.  Rivière C, Dhaif F, Shah H, Ali A, Auvinet E, Aframian A, et al. Kinematic alignment of 
current TKA implants does not restore the native trochlear anatomy. Orthop Traumatol 
Surg Res. 2018 Nov;104(7):983–95.  
5.  Kafelov M, Batailler C, Shatrov J, Al-Jufaili J, Farhat J, Servien E, et al. Functional 
positioning principles for image-based robotic-assisted TKA achieved a higher Forgotten 
Joint Score at 1 year compared to conventional TKA with restricted kinematic alignment. 
Knee Surg Sports Traumatol Arthrosc. 2023 Oct 18;  
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randomised controlled trial of mechanical axis with soft tissue release balancing vs 
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Arthroplasty Clinical and cost Effectiveness Randomised controlled trial (RACER-knee): a 
study protocol. BMJ Open. 2023 Jun 9;13(6):e068255.  

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8.  Zhang JJY, Chen JY, Tay DKJ, Pang HN, Yeo SJ, Liow MHL. Cost-Effectiveness of Robot-
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Priv.-Doz. DDr. Antonio Klasan, EMBA 

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