ANZCTR - Registration

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Trial registered on ANZCTR

Registration number

ACTRN12621000205831

Ethics application status

Approved

Date submitted

7/01/2021

Date registered

26/02/2021

Date last updated

10/05/2023

Date data sharing statement initially provided

26/02/2021

Type of registration

Prospectively registered

Titles & IDs

Public title

RASKAL: Robotic-assisted surgery and kinematic alignment in total knee arthroplasty

Scientific title

RASKAL: Robotic-assisted surgery and kinematic alignment in total knee arthroplasty. A registry-nested, multi-centre, 2 x 2 factorial randomised trial of clinical, functional, radiographic and survivorship outcomes

Secondary ID [1]

None

Universal Trial Number (UTN)

U1111-1263-4830

Trial acronym

RASKAL

Linked study record

None

Health condition

Health condition(s) or problem(s) studied:

End Stage Arthritis

Total Knee Replacement

Osteoarthritis

Condition category

Condition code

Surgery

Surgical techniques

Musculoskeletal

Osteoarthritis

Musculoskeletal

Other muscular and skeletal disorders

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

All 4 interventions listed below are approved and commonly used surgical techniques in Australia. Participating surgeons are formally trained and have performed a minimum of 10 TKA procedures in each intervention group. Participants will be randomly allocated to one of the four interventional procedure listed. Each procedure will take approximately 60 - 120 minutes.

1. robotic-assisted TKA with kinematic knee alignment (RAS-KA group) using MAKO Robotic Platform. This procedure is the intervention arm for both surgical assistance and alignment groups. Alignment in this group is set intraoperatively by the MAKO Robot Product Specialists and surgeon using matched resections. The only adjustments to the matched resections start plan is if restricted KA boundaries are exceeded. Intra-operative gap balancing will then be performed with the aim to achieve symmetrical gap balance. Any adjustments to the original KA plan in order to achieve balanced gaps will be recorded. Adjustments must not exceed the restricted safe zone boundaries. Any further bone cuts or soft tissue releases to achieve balance is permitted and will be recorded.

2. robotic-assisted TKA with mechanical knee alignment (RAS-MA group) MAKO Robotic Platform. This procedure is the second control group for comparison against KA. In addition, this factorial group will test whether RAS haptic boundaries reduce postoperative analgesia consumption and improves early patient outcomes due to a reduction in soft tissue trauma compared to CAS-MA. Preoperative planning software will be set to the MA alignment targets and will be performed with MA resection angles. Only soft tissue balancing is permitted and will be recorded. In order to ensure MA is maintained, no adjustments to alignment are permitted.

3. computer-assisted TKA with kinematic knee alignment (CAS-KA group) using Stryker Precision 3 Navigation System. This procedure represents a restricted boundary KA technique. The surgeon will be provided with a preoperative KA plan, as CAS is considered an imageless (non-CT derived) technique and will be performed with resection angles based on the KA plan. Any further bone cuts or soft tissue releases to achieve balance is permitted and will be recorded.

4. computer-assisted TKA with mechanical knee alignment (CAS-MA group) using Stryker Precision 3 Navigation System. This procedure serves as the control for both factorial groups and will be performed with MA resection angles. Soft tissue balancing is permitted and will be recorded. In order to ensure MA is maintained, no adjustments to alignment are permitted.

Measurements, alignments and any protocol deviations will be recorded by the local study coordinator.

Intervention code [1]

Treatment: Surgery

Comparator / control treatment

Robotic Assisted Surgery for Total Knee Arthroplasty (TKA) as the surgical assignment intervention compared to Computer Assisted Surgery -TKA as the control, and
Kinematic Alignment TKA as the alignment intervention compared to Mechanical Alignment TKA as the control

Control group

Active

Outcomes

Primary outcome [1]

The primary outcome will compare KOOS- 12 mean scores collected at various timepoints between the assistance (Robotic and Computer) and alignment (Kinematic and Mechanical) groups

Timepoint [1]

Pre-operative (baseline), 3 months, 6 months, and 1 year postoperatively.

Secondary outcome [1]

Patient-reported outcome measures : Knee Injury and Osteoarthritis Outcome Scores (KOOS-12) subscales of Pain, Symptoms and Function measured at 3 months, 6 months, 1 and 2 years postoperatively. This is a composite secondary outcome and the outcome measure is a scale from worst to best from 0 to 100, with 100 indicating no symptoms and 0 indicating extreme symptoms.

Timepoint [1]

Pre-operative (baseline), 3 months, 6 months, and 1 year postoperatively.

Secondary outcome [2]

Tibiofemoral Compartmental Pressure Loads.
Compartmental pressure loads will be recorded to validate whether knee balance has been achieved for each group. This will be done using the Verasense pressure insert during each procedure.

Timepoint [2]

This will be recorded during each procedure.

Secondary outcome [3]

Radiographic outcomes
A CT Perth Protocol will be obtained within 6-8 weeks postoperatively will measure HKA, LDFA, MPTA, femoral and tibial component flexion, femoral component rotation and femorotibial component match. The alignment difference (AD = absolute final intraoperative navigation alignments minus postoperative CT alignments) will be calculated for each angular variable. The proportion of participants with an AD within and inclusive of +/- 2 and +/- 3 degrees will be determined for each angular variable and compared between groups.

Timepoint [3]

6-8 weeks postoperatively (Routine). This is a composite secondary outcome.

Secondary outcome [4]

Revision surgery - Implant Survivorship
Each hospital will provide operative data on specific Registry forms. These are completed in theatre at the time of surgery and submitted to the Registry each month to be entered into the Registry database. The Registry will determine if any primary procedure has been subsequently revised by matching procedure records by the patient details provided. This information is then used to calculate the time to revision.

Timepoint [4]

Within 2 years post operative

Secondary outcome [5]

Patient Reported Outcomes: Visual Analogue Scale (VAS) Pain Score: measured at 3 weeks, 6 weeks, 3 months, 6 months, 1 and 2 years postoperatively. VAS is a unidimensional measure of pain intensity measured from 0 (no pain) to 10 (worst imaginable pain). Patients will be asked to rate the pain they have had in their knee over the last 7 days.

Timepoint [5]

Measured at Pre-operative, 3 weeks, 6 weeks, 3 months, 6 months, and 1 year postoperatively.

Secondary outcome [6]

Patient Reported Outcomes: Oxford Knee Score (OKS): OKS is a 12-item tool designed to assess pain and function after TKA. This is a composite secondary outcome and the OKS provides a single summed score; the lower the score, the higher the severity of the patient’s problems.

Timepoint [6]

Measured at Pre-operatively, 3 weeks, 6 weeks, 3 months, 6 months, and 1 year postoperatively.

Secondary outcome [7]

Patient Reported Outcomes via study questionnaire at specified timepoints: Analgesic Requirements
To compare the use of analgesia between groups. Patients will be asked if they used any strong pain medications (excluding paracetamol or anti-inflammatory medications) specifically used for their knee in the last 7 days.
Patients that have indicated the use of any strong pain medications, will be then presented with a list of drugs to select.

Timepoint [7]

Measured at Pre-operatively, 3 weeks, 6 weeks and 3 months postoperatively.

Secondary outcome [8]

Patient Reported Outcome: Forgotten Joint Score 12 (FJS-12): The FJS-12 focuses on patients’ awareness of their knees in everyday life. Low ceiling effects and good relative validity allow monitoring of longer-term outcomes, particularly in well-performing groups after TKA.

Timepoint [8]

Measured at Pre-operatively, 3 months, 6 months, and 1 year postoperatively.

Secondary outcome [9]

Patient Reported Outcome: EQ-5D-5L (EuroQoL). EQ-5D-5L is a standard measure of overall health status that provides a simple descriptive profile and an index value for health status.

Timepoint [9]

Measured at Pre-operatively, 3 months, 6 months, and 1 year postoperatively.

Secondary outcome [10]

Patient Reported Outcomes: Patient-rated Satisfaction and Improvement: this will consist of a 5 option Likert scale from ‘very dissatisfied’ to ‘very satisfied’.

Timepoint [10]

It will be measured at 3 months, 6 months, and 1 year postoperatively.

Secondary outcome [11]

Patient Reported Outcomes: Joint Change Question: The perceived change in the patients knee after surgery will be assessed using a 5 option Likert scale from ‘much worse’ to ‘much better’.

Timepoint [11]

It will be measured at 3 months, 6 months, and 1 year postoperatively.

Secondary outcome [12]

Patient Reported Outcomes via study specific questionnaire during pre-operative timepoint: Patient Expectations:
Patients expectations in 6 months’ time will be assessed by asking the following questions during the pre-operative study questionnaire related to pain, mobility and health status preoperatively.

Expected Joint Pain in 6-months’ after the operation: Patients will be asked to indicate their expected average pain on their joint using a Nurmeric Pain Scale , 0 to 10, 0 means no pain at all and to 10 worst pain imaginable.

Expected Health in 6-months’ after the operation: Patients will be asked to indicate their expectation of their general health using a Visual Analogue Scale, 0 - 100 , 0 means the worst health and 100 means the best health.

Expected Mobility in 6 months after the operation: Patients will be asked to select from the following options on their expected mobility.
- I have no problems walking around
- I will have slight problems with walking around
- I will have moderate problems with walking around
- I will have severe problems with walking around
- I will be unable to walk around

Timepoint [12]

Pre-operatively

Secondary outcome [13]

Patient Reported Outcomes: Responder status. The proportion of “responders” between groups will be compared using OMERACT-OARSI criteria. Responder status is defined as positive using the following criteria:

1. relative improvement in KOOS-pain or KOOS-function of greater than or equal to 50% and absolute change greater than or equal to 20%

OR

2. at least 2 out of 3 of the following:
i. relative KOOS-pain improvement greater than or equal to 20% and absolute change greater than or equal to 10%
ii. relative KOOS-function improvement greater than or equal to 20% and absolute function change greater than or equal to 10%
iii. joint change rated as “much better"

Timepoint [13]

Measured at 3 months, 6 months, and 1 year postoperatively.

Secondary outcome [14]

Patient Reported Outcome: Patient Acceptable Symptom State (PASS). PASS is defined as an outcomes score threshold for the postoperative score above which a patient considers themselves to have a satisfactory outcome. The proportion of participants in each group reaching PASS will be compared for KOOS-12 and OKS. The PASS will be set at 84 for KOOS-12 and 37 for the OKS based on prior published thresholds.

Timepoint [14]

Measured at pre-operatively, 3 months, 6 months, and 1 year postoperatively.

Secondary outcome [15]

Functional Outcome Measures - Knee range of motion
Photographic measurements will be performed in supine position which allows repeatability and blinding. The following will be recorded; maximal active extension (hyperextension being negative, full extension as zero and flexion contracture as positive); maximal active flexion; and arc of knee motion (flexion minus extension).

Timepoint [15]

6 months post operatively.

Secondary outcome [16]

Functional Outcome Measures - 2. Timed Up and Go (TUG) Test

Participants will be asked to stand up from a standard seat (height 44-47cm), walk a distance of 3 meters (marked on the floor) at a comfortable pace, turn, walk back and sit down. Participants will be permitted to use routine walking aids and will be instructed not to use their arms to stand up. This task will be performed twice. Shorter times indicate better performance.

Timepoint [16]

6 months post operatively.

Secondary outcome [17]

Functional Outcomes Measures: 3. Six Minute Walk Test (6MWT)

Participants will be instructed to ascend and descend a flight of 12 steps (no greater than 18cm in height) as quickly as they can while still feeling safe and comfortable. The use of a handrail is allowed if required although participants will be encouraged to use only their legs. Furthermore, an assistive device is allowed if required to complete the test. This test has excellent responsiveness (more so than the 6MWT) and may help differentiate higher levels knee function.

Timepoint [17]

6 months post operatively.

Secondary outcome [18]

Functional Outcome Measures: Single Leg Stance Test (SLST)

Participants will be asked to stand on the unaffected leg with their eyes open and maintain their balance for as long as possible. They will then repeat the test on the operated leg. Three attempts will be made with the best score being used for the final result. The goal is to assess the balance, proprioception and limb strength. This test is a component of the Delaware Osteoarthritis Physical Assessment (DOPA) protocol.

Timepoint [18]

6 months post operatively.

Eligibility

Key inclusion criteria

1. All patients suitable for TKA age 40-80 years with a primary diagnosis of osteoarthritis.
2. Patients who meet the indications for primary unilateral TKA using the Stryker Triathlon cruciate-retaining TKA system.

Minimum age

40 Years

Maximum age

80 Years

Sex

Both males and females

Can healthy volunteers participate?

Key exclusion criteria

1. Knee flexion < 90 degrees and knee flexion contracture > 15 degrees at preoperative assessment
2. Coronal deformity with hip-knee-ankle (HKA) angle > 15 degrees varus and > 10 degrees valgus on standing long-leg radiographs
3. Prior grade 3 injury to posterior cruciate ligament, posterolateral corner, lateral collateral ligament or medial collateral ligament
4. TKA requiring increased prosthetic stability (posterior-stabilised, constrained condylar, or rotating hinge designs), diaphyseal stems or metal augments
5. TKA for causes other than osteoarthritis (inflammatory arthritis, post-traumatic arthritis, tumour or acute fracture)
6. Prior contralateral TKA within 6 months of current TKA surgery
7. Any prior knee surgery apart from arthroscopic surgery or anterior cruciate ligament reconstruction
8. Prior femoral, tibial or patellofemoral osteotomies
9. Symptomatic grade 3-4 ipsilateral ankle or hip arthritis
10. The participant unable to attend clinical follow-up for a minimum of 2 years
11. The participant is unable to provide informed consent (due to cognitive capacity or English proficiency)

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)

Allocation will involve contacting the AOANJRR (holder of the allocation schedule).

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

Allocation of the treatments will follow a computer-generated randomisation schedule with balanced variable blocks. Allocation to treatment via randomisation (1:1:1:1) will occur at the time of patient consent for study inclusion. Stratification will be by surgeon.

Masking / blinding

Blinded (masking used)

Who is / are masked / blinded?

The people assessing the outcomes
The people analysing the results/data

Intervention assignment

Factorial

Other design features

Patients undergoing TKA will be randomly allocated to an assistance group (RAS or CAS) and an alignment group (KA or MA), following a 2x2 factorial design.

Patients will be assigned as follows:
1. robotic-assisted TKA with kinematic knee alignment (RAS-KA group)
2. robotic-assisted TKA with mechanical knee alignment (RAS-MA group)
3. computer-assisted TKA with kinematic knee alignment (CAS-KA group)
4. computer-assisted TKA with mechanical knee alignment (CAS-MA group)

Phase

Not Applicable

Type of endpoint/s

Efficacy

Statistical methods / analysis

Sample size
The KOOS-12 score has been demonstrated to have similar responsiveness and validity to the full KOOS. Roos et al. in 2003 reported a change in KOOS Pain, Symptoms and Function subscales of 45, 37 and 41 (mean 41) in patients undergoing TKA. The minimal clinically important change in KOOS was considered to be between 8 and 10, with a standard deviation (SD) of 16. A sample size of 192 participants (12 surgeon clusters and 16 patients per surgeon) provides 93% power to detect a 0.5SD difference (8 points) in the primary outcome (KOOS-12) for each of the comparisons being tested (CAS vs RAS, and MA vs KA). The target sample size of 300 (20 patients from each of 15 surgeons) allows for loss of three surgeons and 20% patients lost to follow up.

Cost-effectiveness analysis
If a significant and clinically important between-group difference is found comparing RAS and CAS TKA, a cost-effectiveness analysis will be performed from a health service perspective to determine the cost per unit health gain on the KOOS-12 scale, and using the EQ-5D-5L to determine cost per quality-adjusted life year (QALY) gain.

Data analysis
The primary analysis will include a generalised linear mixed model for repeated measures for continuous KOOS-12 scores. This approach allows for repeated measures on the same participants at multiple time points (preoperative, 3 months, 6 months, 1 year and 2 years postoperatively). Patient will be included as a random effect and an unstructured covariance structure will be specified to account for variability at each measurement time. Robotic assistance, kinematic alignment, along with measurement time and their interaction(s) will be included as fixed effects in the model. Both unadjusted and adjusted analyses for measured confounders will be undertaken. Effect sizes will be estimated with 95% confidence limits and statistical significance will be assessed at the 5% level.
The Registry describes the time to first revision using the Kaplan-Meier estimates of survivorship. The cumulative percent revision at a certain time is the complement (in probability) of the Kaplan-Meier survivorship function at that time, multiplied by 100. The cumulative percent revision accounts for right censoring due to death or closure of the database at the time of analysis. The unadjusted cumulative percent revision with an accompanying 95% confidence interval (CI) will be calculated with use of unadjusted pointwise Greenwood estimates. Hazard ratios will be calculated using Cox proportional hazards models adjusting for confounders and will be used to compare the rate of revision between the kinematic alignment group, the robotic assistance group and if there is an interaction between kinematic alignment and robotic assistance. The assumption of proportional hazards will be checked analytically for each model.

Recruitment

Recruitment status

Recruiting

Date of first participant enrolment

Anticipated

6/04/2021

Actual

17/05/2021

Date of last participant enrolment

Anticipated

30/06/2023

Actual

Date of last data collection

Anticipated

31/12/2024

Actual

Sample size

Target

300

Accrual to date

267

Final

Recruitment in Australia

Recruitment state(s)

NSW,WA

Recruitment hospital [1]

St George Private Hospital - Kogarah

Recruitment hospital [2]

Royal Prince Alfred Hospital - Camperdown

Recruitment hospital [3]

North Shore Private Hospital - St Leonards

Recruitment hospital [4]

Mater Sydney - North Sydney

Recruitment hospital [5]

The Northern Beaches Hospital - Frenchs Forest

Recruitment hospital [6]

Gosford Private Hospital - Gosford

Recruitment hospital [7]

Wollongong Private Hospital - Wollongong

Recruitment hospital [8]

St John of God Hospital, Subiaco - Subiaco

Recruitment hospital [9]

St John of God Hospital, Midland - Midland

Recruitment postcode(s) [1]

2050 - Camperdown

Recruitment postcode(s) [2]

2060 - North Sydney

Recruitment postcode(s) [3]

2065 - St Leonards

Recruitment postcode(s) [4]

2086 - Frenchs Forest

Recruitment postcode(s) [5]

2217 - Kogarah

Recruitment postcode(s) [6]

2250 - Gosford

Recruitment postcode(s) [7]

2500 - Wollongong

Recruitment postcode(s) [8]

6008 - Subiaco

Recruitment postcode(s) [9]

6056 - Midland

Funding & Sponsors

Funding source category [1]

Hospital

Name [1]

Ramsay Hospital Research Fund

Address [1]

Ramsay Hospitals Research Foundation
2 Frederick St,
St Leonards NSW 2065

Country [1]

Australia

Primary sponsor type

Other

Name

Australian Orthopaedic Association National Joint Replacement Registry

Address

SAHMRI
North Terrace
ADELAIDE SA 5000

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Sydney Local Health District - Royal Prince Alfred Zone

Ethics committee address [1]

RESEARCH ETHICS AND GOVERNANCE OFFICE
ROYAL PRINCE ALFRED HOSPITAL
50 Missenden Rd,
CAMPERDOWN NSW 2050

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

11/12/2020

Approval date [1]

23/12/2020

Ethics approval number [1]

Ethics committee name [2]

St John of God Health Care

Ethics committee address [2]

12 Salvado Road
SUBIACO WA 6008

Ethics committee country [2]

Australia

Date submitted for ethics approval [2]

04/12/2020

Approval date [2]

23/12/2020

Ethics approval number [2]

Summary

Brief summary

Over the last few years, there has been a significant increase in the use of robotic-assisted surgery (RAS) in total knee arthroplasty (TKA), as well as increasing adoption of kinematic alignment (KA) strategies. Given the significant expenditure required for robotic-assisted surgery, along with increasing use of kinematic alignment, rigorous clinical evidence is required to guide practice in these areas.

The RASKAL study will be assessing patient outcomes by comparing 2 different assistance (Robotic- RAS/Computer-CAS) and alignment (Kinetic -KA/Mechanical-MA) techniques currently used in Total Knee Arthroplasty in Australia. The study will be assessing patient outcomes by comparing 2 different assistance (Robotic- RAS/Computer-CAS) and alignment (Kinetic -KA/Mechanical-MA) techniques currently used in Total Knee Arthroplasty in Australia.

The primary aim of the study is to determine if there is a difference between the groups measured by Patient Reported Outcome Measures (PROMs) over 2 years. The study will be nested within the AOANJRR utilising the RAPID (Real time Automated Platform for Integrated Data capture) system and will be conducted in around 10 sites (across NSW and WA) with 15 surgeons.

Trial website

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Dr Samuel MacDessi

Address

George Private Hospital, Suite 201, Level 2/131 Princes Hwy, Kogarah NSW 2217

Country

Australia

Phone

+610283070333

Fax

samuelmacdessi@sydneyknee.com.au

Contact person for public queries

Name

Dr Khashayar Ghadirinejad

Address

AOANJRR
SAHMRI
North Terrace
ADELAIDE SA 5000

Country

Australia

Phone

+61 0881284528

Fax

ethics@aoanjrr.org.au

Contact person for scientific queries

Name

Ms Durga Bastiras

Address

AOANJRR
SAHMRI
North Terrace
ADELAIDE SA 5000

Country

Australia

Phone

+61 0881284155

Fax

ethics@aoanjrr.org.au

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

No/undecided IPD sharing reason/comment

What supporting documents are/will be available?

Type	Citation	Link	Email	Other Details	Attachment
Study protocol					381170-(Uploaded-06-01-2021-14-07-11)-Study-related document.pdf

Results publications and other study-related documents

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Source	Title	Year of Publication	DOI
Embase	Robotic-assisted surgery and kinematic alignment in total knee arthroplasty (RASKAL study): a protocol of a national registry-nested, multicentre, 2x2 factorial randomised trial assessing clinical, intraoperative, functional, radiographic and survivorship outcomes.	2022	https://dx.doi.org/10.1136/bmjopen-2021-051088

N.B. These documents automatically identified may not have been verified by the study sponsor.

Trial Review

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