Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12618001376235
Ethics application status
Approved
Date submitted
14/08/2018
Date registered
16/08/2018
Date last updated
23/12/2021
Date data sharing statement initially provided
23/12/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
A multi-centre, prospective randomised controlled trial to compare modified kinematically aligned total knee arthroplasty using iTKR™ Software with mechanically aligned total knee arthroplasty.
Scientific title
A multi-centre, prospective randomised controlled trial to compare outcomes following modified kinematically aligned total knee arthroplasty using iTKR™ Software with those following mechanically aligned total knee arthroplasty.
Secondary ID [1] 295632 0
iTKR-AK-18-01
Universal Trial Number (UTN)
U1111-1217-8964
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Total Knee Arthroplasty 309233 0
Osteoarthritis 309234 0
Condition category
Condition code
Musculoskeletal 308110 308110 0 0
Osteoarthritis
Surgery 308124 308124 0 0
Surgical techniques

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This study is a prospective, randomised trial to monitor and compare the outcomes following a primary total knee arthroplasty using two different implant alignment techniques. The one being conventional mechanical alignment, the other being modified kinematic alignment using the iTKR software to produce the surgical plan.

The surgeon undertakes templating from the prescribed long leg x-rays in order to determine the measurement values needed to create the surgical plan. The measurement values are entered into the iTKR website portal along with the unique patient study identifier and a series of questions are answered by the surgeon. The software will then produce a surgical plan based on the measurements and surgeon responses. The surgeon will check the plan against the patient ID before commencing surgery. The surgeon will then use this plan with the robotically assisted navigation system.

The surgical duration will be the same as for a routine total knee arthroplasty surgery. All participants will be clinically assessed using standard functional parameters measuring range of movement pre-operatively, 6 months post-operatively and 2 years post-operatively.
Intervention code [1] 312132 0
Treatment: Devices
Comparator / control treatment
The comparator group will receive the same Apex knee but with mechanical alignment. Currently, mechanical alignment is a standard alignment method used to align Total knee replacements. This is an alignment method that places the femoral component (end of the thigh bone) and the tibial component (top of the shin bone) at right angles to the floor when standing, so that the limb forms a straight line. Research has shown that mechanical alignment and the patient’s natural alignment are rarely the same and this is the likely cause for patient discomfort.
Control group
Active

Outcomes
Primary outcome [1] 307087 0
Patient Reported Outcome measured using the Oxford Knee Score
Timepoint [1] 307087 0
Pre-operative (witin 4 weeks of surgery), and post-operatively at 6 months and 2 years.
Secondary outcome [1] 350635 0
Range of Motion (ROM)measured in the clinic using a standard goniometer.
Timepoint [1] 350635 0
Preoperative (within 4 weeks of surgery), and post-operatively at 6 months, and 2 years
Secondary outcome [2] 350636 0
Patient Reported Outcome measured using the KOOS Jr questionnaire
Timepoint [2] 350636 0
Preoperative (within 4 weeks of surgery), and post-operatively at 6 months, and 2 years
Secondary outcome [3] 350637 0
Quality of life assessed by EQ5D-5L questionnaire
Timepoint [3] 350637 0
Preoperative (within 4 weeks of surgery), and post-operatively at 6 months, and 2
Secondary outcome [4] 350638 0
Patient Satisfaction questionnaire (Patient Satisfaction Scale for Primary Hip and Knee Arthroplasty- Mahomed)
Timepoint [4] 350638 0
Preoperative (within 4 weeks of surgery), and post-operatively at 6 months, and 2 years

Eligibility
Key inclusion criteria
Participants must meet the following criteria to be considered eligible to enrol into the study:
1. Be over the age of 18 years;
2. Be capable of understanding the study requirements and of providing informed consent
3. Be eligible for a primary total knee replacement base on history, physical examination and radiological evaluation –
4. Have primary diagnosis of Osteoarthritis of the knee
5. Agree to attend the research centre for the required post-operative assessments and radiological evaluation.
6. Pre-operative varus/valgus angle 15 degrees or less
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Participants will be excluded from participating in the study if they meet any of the following exclusion criteria:
1. Not meeting the inclusion criteria.
2. BMI greater than 35
3. Haemoglobin A1c greater than 7
4. History of infection in the involved knee or current systemic infection
5. Previous fracture of the femur, tibia, patella or pelvis
6. Previous osteotomy of the affected knee
7. Previous ACL damage or repair
8. Not medically cleared to undergo a total knee replacement
9. American Society of Anaesthesiologists rating of 4 or greater
10. Life expectancy of less than 6 months from all causes
11. Workers Compensation patient
12. Preoperative knee in greater than 15 degrees of varus or valgus
13. Ligamentous laxity of the knee requiring a higher level constrained prosthesis

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)
Central randomisation by computer. Participants will be blinded to their randomisation group. The surgeon will be unblinded.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computer generated Permuted block randomisation
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
CONTINUOUS OUTCOME SUPERIORITY TRIAL
This randomized controlled trial is designed to compare mechanically aligned robotic total knee replacement, with software designed modified kinematically aligned robotic total knee replacement. The null hypothesis is that there will be no difference in pain, function, range of motion, and patient satisfaction at six months, one year, and two years post-operatively between the two groups.
A secondary null hypothesis is that there be no differences between the groups as assessed by limb and implant alignment, physical therapy costs, frequency and type of further minor or major operations.
We will analyse the relationship between alignment and patient reported outcomes (Oxford Knee Score, KOOS Jr., EQ-5D-5L, Satisfaction) with repeated measures analysis of covariance models using a mixed models approach (where participants are considered as random effects and treatment group and baseline assessments are considered as fixed effects). In these analyses we will first perform an “intent-to-treat” analysis, where all participants will be included in the analyses, even if they drop out of the intervention classes prior to completion. Next, we will perform a “per protocol” analysis where we will examine the effects using participants that complete the intervention classes.
Primary Analysis: The primary analysis will be carried out based on an 'intent to treat' approach. That is, all randomized patients will be used in the analysis, whether or not they complete the follow-up analysis or drop out. Because Oxford Knee Score, KOOS Jr., EQ-5D-5L, and satisfaction is measured on a continuous scale and this is a randomized trial, a 2-sample t-test comparing this outcome between the intervention group and the control group at 6,12 and 24 months would be appropriate. In very large trials, one could argue that baseline measurements would not need to be adjusted for, since randomization alone would balance the groups. However, in trials such as this, it is usually recommended that baseline assessments of the outcome of interest be adjusted for (i.e., using an analysis of covariance model (ANCOVA) where baseline assessment of the outcome is considered the covariate in the model) in order to control for potential imbalances between the treated and control groups at baseline. Therefore, our primary analysis will be to fit a repeated measures ANCOVA model that compares the primary variable from baseline to 6,12, 24 months between groups adjusting for the baseline assessment of the primary variable. This ANCOVA approach will allow us to assess whether the mean outcome scores at follow-up, adjusted for baseline scores, differ between the two treatment groups.
Once the primary efficacy analysis is performed (the ANCOVA model with baseline measure as the covariate), secondary analyses of the primary hypothesis will be performed in order to provide additional insight into the relationship between the treatment and outcome. These secondary analyses would first include analysis of covariance (ANCOVA) models that consider the 6,12, 24-month measure of Oxford Knee Score, KOOS Jr., EQ-5D-5L, Satisfaction, as the outcome, the baseline Oxford Knee Score, KOOS Jr., EQ-5D-5L, Satisfaction, as a covariate, and additional participant level characteristics as other covariates. As described earlier in this proposal, there are several potential confounding variables that we may wish to control for. These include the participant’s age, body composition, sex and other baseline assessments. These ANCOVA analyses are not being performed to adjust only for imbalances on measurements between the two intervention groups and the control group, per se, since randomization may handle this, but also other dependent measures and therefore reduce the variability in the model.
Finally, we will conduct a repeated measures ANCOVA model that incorporates the intermediate time points into the model. In these repeated measures models, we will consider the participants as random effects in the model, and thus these models can be considered as mixed effects models. We anticipate examining different covariance structures for this model. Past experience has suggested that a compound symmetry structure is usually appropriate; however, we will examine whether an unstructured covariance is needed as well. Diagnostics and residual plots will be reviewed to ensure that the assumptions for these analyses are being performed to add more precision in estimating the treatment effect since they will control for other baseline characteristics related to the primary outcome models (both the ANCOVA and repeated measures ANCOVA) are met. Should assumptions be violated, transformations of the outcome data will be considered, where the order of the priority in choosing a transformation will be to satisfy the (1) linearity assumption, (2) homogeneity assumption (homoscedasticity), and (3) normality assumption.
The sample size determination for this trial is based on the repeated measures ANCOVA model of 6 months post-treatment measurements, with the aim to have 80% power at the 5% two-sided level of significance to detect a 5-point difference of Oxford Knee Score values. The sample size depends on the variance of the outcome variable and the correlation among the repeated measures. In the absence of good estimates, conservative assumptions regarding the correlations were made. Morgan and Case have shown that the sample size based on the test for main effect from a 2 repeated measures ANCOVA design can be computed using the formula for a two-sample t-test replacing the variance of the outcome measure by N times the variance ratio of the estimated main effect in a repeated measures ANCOVA model [Morgan TM, Case LD. Conservative Sample Size Determination for Repeated Measures Analysis of Covariance. Ann Biom Biostat. 2013 Jul 5;1(1). pii: 1002. PMID: 25045756].
Assuming a compound symmetry covariance structure (as it is commonly assumed between repeated measures) and using the value of the common correlation that maximizes the variance, the minimum required sample size is 44 patients per treatment group. When allowing for 15% loss to follow-up, the required sample size for this trial is 51 patients in each treatment group.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
3/09/2018
Actual
26/06/2019
Date of last participant enrolment
Anticipated
31/12/2021
Actual
Date of last data collection
Anticipated
30/06/2023
Actual
Sample size
Target
102
Accrual to date
98
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD
Recruitment hospital [1] 11657 0
Nepean Hospital - Kingswood
Recruitment hospital [2] 11658 0
Nepean Private Hospital - Kingswood
Recruitment hospital [3] 11660 0
Gold Coast Hospital - Southport
Recruitment hospital [4] 11661 0
Robina Hospital - Robina
Recruitment postcode(s) [1] 23704 0
2747 - Kingswood
Recruitment postcode(s) [2] 23706 0
4215 - Southport
Recruitment postcode(s) [3] 23707 0
4226 - Robina

Funding & Sponsors
Funding source category [1] 300215 0
Commercial sector/Industry
Name [1] 300215 0
Global Orthopaedic Technology
Country [1] 300215 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Global Orthopaedic Technology
Address
17 Bridge Street
Pymble
NSW 2073
Country
Australia
Secondary sponsor category [1] 299625 0
None
Name [1] 299625 0
Address [1] 299625 0
Country [1] 299625 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 301037 0
Bellberry Ethics
Ethics committee address [1] 301037 0
Ethics committee country [1] 301037 0
Australia
Date submitted for ethics approval [1] 301037 0
08/08/2018
Approval date [1] 301037 0
24/09/2018
Ethics approval number [1] 301037 0
2018-08-628
Ethics committee name [2] 301202 0
Gold Coast Hospital and Health Health Service Human Research Ethics Committee
Ethics committee address [2] 301202 0
Ethics committee country [2] 301202 0
Australia
Date submitted for ethics approval [2] 301202 0
15/08/2018
Approval date [2] 301202 0
07/03/2019
Ethics approval number [2] 301202 0
HREC/2018/QGC/44952

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 85666 0
Dr Simon Coffey
Address 85666 0
Dr Simon Coffey Consulting Rooms
58A Derby Street
Penrith, NSW 2750
Country 85666 0
Australia
Phone 85666 0
+61 02 47322566
Fax 85666 0
Email 85666 0
[email protected]
Contact person for public queries
Name 85667 0
Lyndon Crossley
Address 85667 0
Global Director of Clinical Affairs
Corin
17 Bridge Street,
Pymble, NSW 2073
Country 85667 0
Australia
Phone 85667 0
+61 294977400
Fax 85667 0
Email 85667 0
[email protected]
Contact person for scientific queries
Name 85668 0
Lyndon Crossley
Address 85668 0
Global Director of Clinical Affairs
17 Bridge Street,
Pymble, NSW 2073
Country 85668 0
Australia
Phone 85668 0
+61 294977400
Fax 85668 0
Email 85668 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
individual participant data underlying published results after deindentification only
When will data be available (start and end dates)?
Beginning 3 months and ending 5 years following main results publication;
Available to whom?
case-by-case basis at the discretion of Primary Sponsor, etc.
Available for what types of analyses?
only to achieve the aims in the approved proposal
How or where can data be obtained?
Access subject to approvals by Principal Investigator via [email protected]


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.