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Trial registered on ANZCTR


Registration number
ACTRN12621000060842
Ethics application status
Approved
Date submitted
16/10/2020
Date registered
25/01/2021
Date last updated
25/01/2021
Date data sharing statement initially provided
25/01/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
A Prospective Randomised Control Trial Comparing the Effect of Functional Alignment with Mechanical Axis Alignment on Outcomes after Total Knee Arthroplasty.
Scientific title
A Prospective Randomised Control Trial Comparing the Effect of Functional Alignment with Mechanical Axis Alignment on Forgotten Joint Score after Total Knee Arthroplasty.
Secondary ID [1] 302097 0
Nil Known
Universal Trial Number (UTN)
U1111-1257-2291
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Osteoarthritis
318713 0
Condition category
Condition code
Musculoskeletal 316727 316727 0 0
Osteoarthritis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
1. Brief Name
This trial is studying the difference between the two knee alignment arthroplasty theories of mechanical alignment (MA), and functional alignment (FA).
2. Why
There are no prospective studies looking at Functional alignment. Prospective studies comparing functional outcomes between the MA and KA groups have been performed but the main limitation of these studies has been the inability to accurately measure the desired deviation from neutral alignment as well as achieving the implant position to a high degree of accuracy. There is a paucity of studies using standardised techniques for intraoperative alignment and limited data relating these findings to clinical outcomes with long- term follow up.

There is a need for high quality evidence on the clinical and radiological benefits of functionally aligned TKA. This study would show if there is any superior outcomes to be obtained from functional alignment. Clinical and functional outcomes should also be correlated to longer-term outcomes to better establish the “safe zone” for functional alignment.

Currently the vast majority of TKA throughout the world is undertaken utilizing MA alignment. Any change to a newer technique from the current ‘gold standard’ would need to be justified by improved clinical outcomes as there is no long term longevity data for Functional Alignment. Both surgeons and patients are only able to consider the relative risks and benefits of this technique once they are defined by sound scientific evidence. This study will contribute to the body of this evidence.

3. What
Materials: Knee Arthroplasty implants and surgical planning device
212698 - Stryker Australia Pty Ltd - TRIATHLON FEMORAL COMPONENT CRUCIATE RETAINING (CR) -Uncoated knee femur prosthesis
212701 - Stryker Australia Pty Ltd - TRIATHLON X3 ASYMMETRIC PATELLA - Polyethylene patella prosthesis
212702 - Stryker Australia Pty Ltd - TRIATHLON X3 SYMMETRIC PATELLA - Polyethylene patella prosthesis
213155 - Stryker Australia Pty Ltd - TRIATHLON FEMORAL COMPONENT POSTERIOR STABILISED (PS) -Uncoated knee femur prosthesis
216480 - Stryker Australia Pty Ltd - TRIATHLON X3 CRUCIATE RETAINING (CR) TIBIAL INSERT - Prosthesis, knee, internal, insert component
218001 - Stryker Australia Pty Ltd - TRIATHLON UNIVERSAL TIBIAL BASEPLATE - Uncoated knee tibia prosthesis, metallic
218019 - Stryker Australia Pty Ltd - TRIATHLON X3 CONDYLAR STABILISING (CS) TIBIAL INSERT - Prosthesis, knee, internal, insert component
218200 - Stryker Australia Pty Ltd - TRIATHLON X3 POSTERIOR STABILISED (PS) TIBIAL INSERT - Prosthesis, knee, internal, insert component
Styker MAKO robotic arm (Stryker MAKO, Fort Lauderdale, FL).
Patient PROMS
- Forgotten Joint Score: The “Forgotten Joint” as the Ultimate Goal in Joint Arthroplasty: The Journal of Arthroplasy Volume 27, Issue 3. Pages 430-436. E1, March 2012. H Behrend et.al.
- EQ5D-5L: https://euroqol.org/
- Oxford Knee Score: http://www.isis-innovation.com/outcomes
- VAS Pain: Socrates: Copyright Ortholink. Pty Ltd 1997
- KOOS Jr: Validation of the KOOS, JR: A Short –form Knee Arthroplasty Outcomes Survey Clin Orthop Relat Res (2016) 474:1461-1471 Stephen Lyman PhD et al.
- Kujala Anterior Knee Pain: https://www.orthotoolkit.com/kujala/
- Likert Scale
4. Procedures
Patient Outcome Testing Tools
a. Hand Held Dynamometer Testing, Lachmeter Arthometer Testing, 30 Second Sit to Stand Test.
b. Surgical Planning
i. All Patients will have pre-operative CT scan for planning as per current standard technique.
ii. Prior to surgery Patient’s pre-operative plan will be formulated on the basis of their randomisation.
iii. The control group will be planned to mechanical axis alignment.
1. To do this the tibia will be sized to best match with the tibial plateau size without more than 2mm overhang anterolaterally or posteriorly and no overhanging of cortices medial and laterally. The coronal angulation of the tibia will be 0° of varus/valgus and posterior slope will be 3°. Resection depth will be set to a depth of 7mm maximal resection.
2. The femur will initially be planned with the same size as the tibia and 8mm resection depths posteriorly and distally. Coronal angulation will be zero degrees varus/valgus and flexion of 3° for males and 5° for females. Size is then adjusted to allow best match to condylar radius of curvature. Femoral rotation will be set to parallel to surgical epicondylar axis. Femoral flexion angle is then altered within the range of 0-7° to optimise the anterior cut exit point. If unable to accommodate size without notching anterior cortex or having the tip of the implant achieving bony contact, size will be altered to achieve this. Medial lateral width of component will not overhang distal femur or will be downsized.
iv. The investigation group will be planned with Kinematic Axis alignment. This will be changed to functional alignment intra-operatively once soft tissue balance assessed.
1. To achieve this the tibia will be sized to best match with the tibial plateau size without more than 2mm overhang anterolaterally or posteriorly and no overhanging of cortices medial and laterally. The resection depths will be set to 7mm medially and laterally. (N.B. This may exceed 6° of varus angulation but this will be adjusted intra-operatively).
2. The same size femur is then used as starting size. 6.5mm resections are planned medially and laterally from the distal and posterior condyles.(N.B. this may result in excessive valgus but this will be adjusted intra-operatively). Femoral flexion angle is then altered within the range of 0-7° to optimise the anterior cut exit point. If unable to accommodate size without notching anterior cortex or having the tip of the implant achieving bony contact size will be altered to achieve this. Medial lateral width of component will not overhang distal femur or will be downsized.
3. Tibial slope is then matched to native slope whilst not exceeding combined femoral flexion and tibial slope of more than 10°. If this value exceeds 10° then tibial slope is reduced.
d. A standard anaesthetic approach involving Spinal anaesthetic involving 2.5mls of heavy bupivacaine and 30-60mcg buprenorphine(dependant on patient size and comorbidities). An Adductor block is then performed with ultrasound guidance using bupivacaine. Sedation or GA is then undertaken as per patient preference for comfort and anxiety. If the anaesthetic is required to be altered for any reason it will be done so at the discretion of the Consultant Anaesthetist in the best interests of the patient and any variation will be recorded.
e. Surgical approach is consistent for both groups. Following Anaesthetic and IDC insertion a pre-prep is undertaken with alcohol based skin prep. A tourniquet is then applied and inflated to 300mm Hg immediately prior to skin preparation and draping. The surgical area is then protected with an iodine occlusive dressing (Ioban).
f. The incision is midline with a medial parapatellar approach. Trackers and checkpoints are inserted into the femur and tibia, The ACL is resected if present.
g. Registration is then undertaken. Osteophytes are then removed from distal femur and medial tibia. A pre-resection balancing workflow is then undertaken with maximal soft tissue gaps measured at 10 degrees of flexion and 90 degrees of flexion.
h. The aim is to balance the knee within the alignment principles of each treatment arm such that extension is balanced from medial to lateral to within 1mm (2mm acceptable) and balanced from extension to flexion on the medial side to within 1mm (2 mm acceptable). The lateral flexion gap is allowed to be lax with the resections described above. The lateral flexion gap should not be tighter than the medial flexion gap.
i. Once plan is balanced the TKA is executed utilising robotic arm assisted technique with soft tissue releases as required if balance not achieved within component positioning limits of each technique.
j. The first 30 patients in each group that consent to the use of verasense pressure measures (adding 5 minutes to procedure time) will have intra-operative compartment pressures measured at 10, 45 and 90 degrees of flexion.
j. The procedure is expected to be between 90 and 120 minute duration
5. Who Provided
The surgeries will be performed by two orthopaedic surgeons familiar with the surgical techniques.
Patient assessment will be performed by three orthopaedic trained physiotherapists.
6. How
Patients suitable for knee arthroplasty will be identified by the consultant orthopaedic surgeons. If suitable, the research physiotherapists will contact the patients to inform them of the study. Patients will be emailed the consent form and PIF. Patients will then consult the research physiotherapist at their preoperative appointment, and be enrolled in the study if they wish.
Interventions will be provided to one participant at a time as it is a surgical technique for the entire study cohort.
Clinical testing will be provided face to face, one patient at a time.
Patient reported outcome measures will be emailed to patients using the software, SOCRATES. Patients can fill their surveys out at home. If required they can also complete their surveys on available ipads in the consulting rooms.
7. Where
All surgeries will be carried out at St. John of God Hospital, Subiaco.
8.When and how much
The surgery will occur once. Patients will complete their PROMS and clinical testing outcomes at the pre-operatively, 6 week, 3month, 12 month and 2 year time points.
9.Tailoring
Patients will be randomised to two groups, MA and FA.
Intervention code [1] 318431 0
Treatment: Surgery
Comparator / control treatment
Mechanical axis aligned Total Knee Arthroplasty
Control group
Active

Outcomes
Primary outcome [1] 324897 0
Relative change in Forgotten joint score between FA and MA patients post-operatively compared to preoperatively.
Timepoint [1] 324897 0
Measured by patient report pre-operatively and at 2 years postoperatively
Primary outcome [2] 325345 0
Oxford Knee Score
Timepoint [2] 325345 0
Pre-operatively and 2 years post operatively.
Primary outcome [3] 325349 0
Relative change in range of motion between FA and MA patients post-operatively compared to preoperatively.
Timepoint [3] 325349 0
Measured via goniometry preoperatively and postoperatively at 2 years
Secondary outcome [1] 386154 0
Determine lower limb alignment achieved with both alignment techniques.
Timepoint [1] 386154 0
Lower limb alignment as assessed using standing long leg x-rays performed postoperatively at 3 months. Measurements of the hip-knee-angle (HKA), medial proximal tibial angle (MPTA) and lateral distal femoral angle (LDFA). Also evidence of imbalance with implant lift off will be measured.
Secondary outcome [2] 386155 0
Determine if there are any differences in analgesic requirements based on alignment method used.
Inpatient medical records will be utilised to obtain analgesia requirements as inpatient
Questinaires will be used to obtain analgesia usage at remaining timepoints.
Analgesia usage will be converted to morphine equivalent dosages for comparison
Timepoint [2] 386155 0
Analgesia requirements during inpatient admission and postoperatively at 6 weeks, 3 months, 1 year and 2 years will be measured.
Secondary outcome [3] 386156 0
Determine whether alignment method utilized has an effect on the sagittal stability of the knee post replacement
Timepoint [3] 386156 0
Assessment of sagittal stability at Preop, and post-operatively at 3 months, 1 year and 2 years will be undertaken with an arthrometer “Lachmeter”.
Secondary outcome [4] 386157 0
Determine whether alignment method utilized has an effect on functional outcomes.
Measured as Maximal voluntary isometric knee flexion and extension forces as measured via hand-held dynamometry.
Timepoint [4] 386157 0
Maximum voluntary isometric knee flexion and extension force using a hand-held dynamometer at Preop, 3 months, 1 year and 2 years.
Sit to stand values as measure of function at Preop, 3 months, 1 year and 2 years.
Secondary outcome [5] 386158 0
Intra-operative balance achieved with different alignment techniques.
Timepoint [5] 386158 0
Surgeon blinded measurement of intraoperative balance achieved with Verasense sensor (smaller cohort)
Secondary outcome [6] 386159 0
To determine if there is a difference in knee kinematics between the two techniques. Measurement of knee kinematics with Verasense sensor to assess presence or absence of medial pivot (smaller cohort)
Timepoint [6] 386159 0
Intra-operatively via Verasense device
Secondary outcome [7] 387587 0
Difference in clinical outcomes as measured in Knee Osteoarthritis Outcome Junior Score (KoosJR),
Timepoint [7] 387587 0
Measured Pre-operatively and at 3 month, 1 year and 2 years post operatively.
Secondary outcome [8] 387588 0
European Quality of Life questionnaire with 5 dimensions for adults (EQ-5D-5L).
Timepoint [8] 387588 0
Measured pre-operatively and post-operatively at 6 weeks, 3 months, 1 year and 2 years.
Secondary outcome [9] 388847 0
Visual Analogue Scale for pain (VAS)
Timepoint [9] 388847 0
Will be measured pre-operatively, 6weeks, 3months, 1 year and 2years post-operatively
Secondary outcome [10] 388848 0
Kujala score- a measure of anterior knee pain and best clinical score for patellofemoral function
Timepoint [10] 388848 0
pre-operatively and 3months, 1 year and 2 years post-operatively

Eligibility
Key inclusion criteria
-Patient has symptomatic knee osteoarthritis requiring primary TKA
-Patient and surgeon are in agreement that TKA is the most appropriate treatment
-Patient is fit for surgical intervention following review by surgeon
-Patient is between 45-75 years of age at time of surgery, computer literate, and able to complete patient reported outcome measures independently.
-Patient must be capable of giving informed consent and agree to comply with the postoperative review program.
-Patient must be a permanent resident in an area accessible to the study site
-Patient must have sufficient postoperative mobility to attend follow-up clinics and allow for radiographs to be taken
-Patient has tried non-pharmacologic therapy’s including ; patient education, self-management programs, aerobic exercise, weight loss, physiotherapy and occupational therapy
-Patient has tried appropriate pharmacologic therapies including ; regular paracetamol and NSAIDS if appropriate
Minimum age
45 Years
Maximum age
75 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Patient is not suitable for routine primary TKA. E.g. patient has ligament deficiency that requires a constrained prosthesis
- Interoperative requirement for a more constrained implant.
- Intraoperative requirement for the PCL to be released. These patients will be still included in the study, but analyzed with an intention to treat principal.
- Patient has bone loss that requires augmentation
- Patient requires revision surgery following previously failed correctional osteotomy or ipsilateral TKA (eg. Post high tibial or distal femoral osteotomy)
- Patient requires a polyethylene inset of 13mm or greater.
- Patient is immobile or has another neurological condition affecting musculoskeletal function
- Patient is less than 44 years of age or greater than 76 years of age
- Patient is a compensable patient. I.e. Worker’s compensation claim or motor vehicle accident.
- Patient is already enrolled on another concurrent clinical trial
- Patient is unable or unwilling to sign the informed consent form specific to this study
- Patient is unable to attend the follow-up program
- Patient is non-resident in local area or expected to leave the catchment area postoperatively
- Patients who lacks capacity to provide consent, or the ability to understand the study protocol due to a cognitive condition (eg. Dementia)
- Patient is unable to communicate effectively in English.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Screen shots of the randomization process and seed number will be taken throughout, and held from the CI to minimize randomization bias. The orthopedic fellow will then privately communicate to the CI the allocated group, to enable alignment and templating planning to be performed using the MAKO software.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Using a randomization website (www.random.org), a random number (between 1 and 100000) will be generated. This will form the “seed” number for the blocked randomization process. Using a randomization website (www.sealedenvelope.com) the randomization list will be created. Patients will be allocated in a sequential order of consent, strictly adhering to the allocation of groups.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
Sample Size In total, 100 patients will be enrolled in a 1:1 ratio between the two treatment groups. This will ensure that the minimum of 90 patients required to answer the study question are followed up for the duration of the study. The enrollment goal is to have at least 45 patients in each of the two treatment groups completing the study.

Using data from our initial cohort recording functional outcomes, the mean FJS score at 1 year in the mFA TKA was 59 (SD 6) and in the kFA TKA was 75 (SD 8). It is assumed that MA results will be no better than mFA results. The study was powered to demonstrate a 12 point difference in the Forgotten Joint score, which is the minimal clinical important change in the score. Using a one tailed analysis (assuming superior results with the kFA), an alpha value of 0.05 and power of 0.80, and accounting for expected drop-out rate of 10%, this study will need 100 patients to answer the study question.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 17619 0
St John of God Hospital, Subiaco - Subiaco
Recruitment postcode(s) [1] 31364 0
6008 - Subiaco

Funding & Sponsors
Funding source category [1] 307199 0
Hospital
Name [1] 307199 0
St John of God Subiaco Private Hospital
Address [1] 307199 0
Salvado Rd
Subiaco WA 6008
Country [1] 307199 0
Australia
Primary sponsor type
Individual
Name
Gavin Clark
Address
Perth Hip and Knee
Suite 1/1 Wexford St, Subiaco WA 6008
Country
Australia
Secondary sponsor category [1] 307546 0
None
Name [1] 307546 0
Address [1] 307546 0
Country [1] 307546 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 306720 0
St John of God Health Care Human Research Ethics Committee
Ethics committee address [1] 306720 0
St John of God Health Care Human Research Ethics Committee
C/o St John of God Subiaco Hospital
12 Salvado Road
Subiaco Western Australia 6008
Ethics committee country [1] 306720 0
Australia
Date submitted for ethics approval [1] 306720 0
06/01/2020
Approval date [1] 306720 0
11/03/2020
Ethics approval number [1] 306720 0

Summary
Brief summary
The objective of this study is to compare clinical and radiological outcomes in robotic-arm assisted TKA using mechanical alignment (MA TKA) versus robotic-arm assisted TKA with functional alignment (FA TKA). Both FA TKA and MA TKA are performed through similar skin incisions, robotic-guidance, and use identical implants. In MA TKA, bone is prepared and implants positioned to ensure that that the overall alignment of the leg is in neutral. In FA TKA, the bone is prepared and implants positioned to restore the natural alignment of the patient’s leg. Both of these surgical techniques provide excellent outcomes in TKA but it is not known which of the two techniques is better for patient recovery. Mako robotic-assisted TKA is an established treatment for arthritis of the knee joint. The positions of the implants and overall alignment of the leg are important as they influence how quickly the implants wear out and need replacing. The aim of this study is to determine if patient recovery is better with functionally aligned Mako robotic-assisted total knee arthroplasty (FA TKA) or mechanically aligned Mako robotic-assisted total knee arthroplasty (MA TKA)
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 104786 0
Dr Gavin Clark
Address 104786 0
Perth Hip and Knee Clinic
1/1 Wexford St,
Subiaco,
WA 6008.
Country 104786 0
Australia
Phone 104786 0
+61 8 6489 1777
Fax 104786 0
+61 8 6489 1771
Email 104786 0
gavin@hipnknee.com.au
Contact person for public queries
Name 104787 0
Dr Gavin Clark
Address 104787 0
Perth Hip and Knee Clinic
1/1 Wexford St,
Subiaco,
WA 6008.
Country 104787 0
Australia
Phone 104787 0
+61 8 6489 1777
Fax 104787 0
+61 8 6489 1771
Email 104787 0
clark@hipnknee.com.au
Contact person for scientific queries
Name 104788 0
Dr Gavin Clark
Address 104788 0
Perth Hip and Knee Clinic
1/1 Wexford St,
Subiaco,
WA 6008.
Country 104788 0
Australia
Phone 104788 0
+61 8 6489 1777
Fax 104788 0
+61 8 6489 1771
Email 104788 0
gavin@hipnknee.com.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Confidentiality of participants
What supporting documents are/will be available?
No other documents available
Summary results
No Results