Access to this full-text is provided by Springer Nature.
Content available from Trials
This content is subject to copyright. Terms and conditions apply.
S T U D Y P R O T O C O L Open Access
A prospective double-blinded randomised
control trial comparing robotic arm-assisted
functionally aligned total knee arthroplasty
versus robotic arm-assisted mechanically
aligned total knee arthroplasty
Babar Kayani
*
, Sujith Konan, Jenni Tahmassebi, Sam Oussedik, Peter D. Moriarty and Fares S. Haddad
Abstract
Background: Total knee arthroplasty (TKA) with mechanical alignment (MA) aims to achieve neutral limb alignment
in all patients, whereas TKA with functional alignment (FA) aims to restore native, patient-specific anatomy and
knee kinematics by manipulating bone resections and fine-tuning implant positioning. The objective of this study is
to determine the optimal alignment technique in TKA by comparing patient satisfaction, functional outcomes,
implant survivorship, complications, and cost-effectiveness in MA TKA versus FA TKA. Robotic technology will be
used to execute the planned implant positioning and limb alignment with high-levels of accuracy in all study
patients.
Methods and analysis: This prospective double-blinded randomised control trial will include 100 patients with
symptomatic knee osteoarthritis undergoing primary robotic arm-assisted TKA. Following informed consent,
patients will be randomised to MA TKA (the control group) or FA TKA (the investigation group) at a ratio of 1:1
using an online random number generator. Blinded observers will review patients at regular intervals for 2 years
after surgery to record predefined study outcomes relating to postoperative rehabilitation, clinical progress,
functional outcomes, accuracy of implant positioning and limb alignment, gait, implant stability, cost-effectiveness,
and complications. A superiority study design will be used to evaluate whether FA TKA provides superior outcomes
compared to MA TKA. Primary and secondary objectives will be used to quantify and draw inferences on
differences in the efficacy of treatment between the two groups. Intention-to-treat and per-protocol population
analysis will be undertaken. The following statistical methods will be employed to analyse the data: descriptive
statistics, independent ttest, paired ttest, analysis of variance, Fisher exact test, chi-square test, and graphical
displays. Ethical approval was obtained from the London-Surrey Research Ethics Committee, UK. The study is
sponsored by University College London, UK.
Discussion: This is the first study to describe the use of robotic technology to achieve FA TKA, and the only
existing clinical trial comparing robotic MA TKA versus robotic FA TKA. The findings of this study will enable an
improved understanding of the optimal alignment technique in TKA for achieving high-levels of patient satisfaction,
improving functional outcomes, increasing implant survivorship, improving cost-effectiveness, and reducing
complications.
Registration: Clinical Trials.gov,NCT04092153. Registered on 17 September 2019.
© The Author(s). 2020 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0
International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and
reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to
the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver
(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
* Correspondence: babar.kayani@gmail.com
Department of Trauma and Orthopaedic Surgery, University College Hospital,
235 Euston Road, Fitzrovia, London NW1 2BU, UK
Kayani et al. Trials (2020) 21:194
https://doi.org/10.1186/s13063-020-4123-8
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
Background
Total knee arthroplasty (TKA) is an established and
highly effective treatment for patients with symptomatic
end-stage knee osteoarthritis. The procedure is per-
formed in over 90,000 patients per year in the UK [1].
Middle- to long-term follow-up studies have shown
good clinical outcomes following TKA [20,22,39], and
the 10-year revision rate for cemented, unconstrained,
fixed bearing TKA is 3% [1]. Despite these results, there
is a higher incidence of patient dissatisfaction compared
to total hip arthroplasty, with up to 20% of patients
reporting dissatisfaction in an otherwise uncomplicated
TKA [5,9,10,35]. The exact aetiology of this is not clear
but recent studies have shown one possible reason to be
suboptimal limb alignment, which may adversely affect
postoperative knee biomechanics and kinematic function
[4,7,9–11,35,44]. Conceptually, an improved under-
standing and execution of the optimal alignment in TKA
may help to increase patient satisfaction, improve func-
tional outcomes and reduce long-term complications.
Total knee arthroplasty with mechanical alignment
(MA) aims to achieve neutral alignment of the limb.
This is achieved by placing implants perpendicular to
the mechanical axis of the femur and tibia, and exter-
nally rotating the femoral component to obtain a rect-
angular, balanced flexion-extension gap, which also aids
patella tracking [11]. Measured bone resections or gap
balancing techniques with controlled periarticular soft
tissue releases help to achieve balanced flexion-
extension gaps and restore equal mediolateral soft tissue
tension. The principle of neutral mechanical alignment
is to distribute load evenly across the implants, which
provides a mechanical advantage in flexion and limits
asymmetrical bearing surface wear [44]. However, recent
studies have shown that there are large variations in na-
tive knee anatomy with only 5–5.5% of the general
population having natural neutral mechanical alignment
[4,6]. Therefore, in the large majority of patients under-
going MA TKA, the knee is forced into an unnatural
position with resultant changes in knee biomechanics
that alter the native femoral flexion axis, ligament ten-
sion, quadriceps function, patella tracking and overall
knee kinematics [4,6,17,18].
Total knee arthroplasty with functional alignment (FA)
aims to restore joint line height, preserve native obli-
quity, and achieve balanced flexion-extension gaps with
equal mediolateral soft tissue tension by manipulating
bone resections and fine-tuning implant positioning.
Conceptually, FA TKA reduces the need for intraopera-
tive periarticular soft tissue releases while restoring the
patient’s native pre-arthritic knee kinematics. This tech-
nique is a modification of TKA with kinematic align-
ment, in which bone resections and implant positioning
are undertaken to restore the patient’s natural distal and
femoral joint lines, tibial joint line and limb alignment.
Patient-specific implants, computer navigation and three-
dimensional printed cutting blocks have been used to help
achieve kinematic alignment in TKA. Studies have dem-
onstrated that TKA with kinematic alignment reproduces
more natural knee kinematics including medial pivot
movement and femoral rollback compared to MA TKA
[14,34,15,26,29]. Preserving patient-specific alignment
and knee kinematics in TKA with kinematic alignment
may also decrease the risk of common peroneal nerve
palsy, which is associated with forcing the limb into neu-
tral alignment with extensive bone resections and peri-
articular releases in MA TKA [23,25]. Early clinical and
functional outcome studies have reported promising out-
comes in TKA with kinematic alignment [14,27,28], but
results of longer-term studies have yet to be published.
There is no uniform consensus on the optimal align-
ment technique for TKA [8,12,16,19,30,33,36–38,41].
Some studies have shown improved clinical outcomes
with TKA with kinematic alignment compared to MA
TKA at short-term follow-up, while other systematic re-
views and meta-analyses have shown no difference in out-
comes between the two alignment techniques [14,27,28,
34,44]. The main limitations of these existing studies are
that different implant designs were used within each treat-
ment group, manually positioned cutting blocks with poor
reproducibility were used to achieve the planned limb
alignment, intraoperative limb alignment was not assessed,
and limited data on functional outcomes or implant sur-
vivorship were reported. It is possible to improve on these
existing studies by assessing a more comprehensive range
of validated clinical and functional outcome measures,
blinding both patients and observers recording outcomes,
and using radiosteriometric analysis (RSA) to assess im-
plant micromotion for long-term implant survivorship
[32,42,43]. Importantly, FA TKA offers an avenue for
achieving patient-specific kinematics with balanced
flexion-extension gaps and equal mediolateral soft tissue
tension by manipulating bone resections and fine-tuning
implant positioning, while limiting the need for periarticu-
lar soft tissue releases. Robotic technology also offers an
avenue for executing the planned MA TKA or FA TKA
with greater accuracy and reduced outliers. The findings
of this study will enable an improved understanding of the
optimal alignment technique in TKA for achieving high
levels of patient satisfaction, improving functional out-
comes, increasing implant survivorship, improving cost-
effectiveness and reducing complications.
Methods/design
Objectives
The primary objective of this study is to compare the total
Western Ontario and McMaster Universities Arthritis
Index (WOMAC) score in MA TKA versus FA TKA at 2
Kayani et al. Trials (2020) 21:194 Page 2 of 10
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
years after surgery. As FA TKA enables improved restor-
ation of native, patient-specific knee kinematics [15,26,
29], the study hypothesis is that total WOMAC scores will
be superior in patients undergoing FA TKA compared to
MA TKA at 2 years follow-up.
The secondary objectives are to compare the following
outcomes between the two treatment groups:
1. Accuracy of implant positioning and limb alignment
2. Surgical efficiency
3. Postoperative functional rehabilitation
4. Functional outcomes
5. Quality of life
6. Implant migration
7. Gait
8. Resource use and cost-effectiveness
9. Complications
Trial design
This study is a prospective, single-centre, double-blinded,
randomised control trial. The study will be undertaken in
the Department of Trauma and Orthopaedics, University
College Hospital, London, UK. The study will include 100
patients randomly allocated to either MA TKA (the con-
trol group) or FA TKA (the investigation group). All pa-
tients will undergo robotic arm-assisted TKA to improve
the accuracy of achieving the planned implant positioning
and limb alignment. The study commenced patient re-
cruitment in December 2018 and is expected to complete
patient recruitment in December 2020. All patients will be
followed up for 2 years after surgery and therefore the an-
ticipated completion date for the study is December 2022.
The study is sponsored by University College London,
UK. The patient enrolment flowchart is presented in Fig. 1.
The schedule of enrolment, interventions, and assess-
ments for all study patients is shown in Fig. 2.Thisstudy
followed the Standard Protocol Items: Recommendations
for Interventional Trials (SPIRIT) (Additional file 1).
Eligibility criteria
The inclusion criteria for this study are as follows: 1) the
participant has symptomatic knee osteoarthritis requir-
ing primary TKA; 2) the participant is fit for surgical
intervention following a review by the surgeon and an-
aesthetist; 3) the participant is aged between 18 and 80
years at the time of surgery; 4) the participant is able to
give informed consent and agrees to comply with the
postoperative review programme; and 5) the participant
has sufficient mobility to attend follow-up clinics. The
exclusion criteria for this study are as follows: 1) the par-
ticipant is undergoing revision surgery or second-stage
TKA; 2) the participant is not suitable for study implants
(e.g. requires a constrained prosthesis); 3) the participant
is immobile or has another neurological condition
affecting musculoskeletal function; 4) the participant is
already enrolled on another concurrent clinical trial; 5)
the participant is unable or unwilling to sign the informed
consent form specific to this study; and 6) the participant
is unable to attend the study follow-up programme.
Recruitment
Participants will be recruited from the orthopaedic out-
patient clinic at University College Hospital, London,
UK. All patients will be screened by the clinical team
(orthopaedic consultant surgeon, clinical research fellow,
and orthopaedic registrar) for study participation based
on the predefined inclusion and exclusion criteria listed
above. Patients that fulfil the eligibility criteria and ex-
press an interest in participating in the study will be pro-
vided with an Ethics Committee-approved patient
information sheet. This provides details about the study,
treatment, follow-up and contact details for further in-
formation. All members of the clinical team are familiar
with the study and will address any preliminary ques-
tions about the study. Details of those patients express-
ing an interest to participate in the study will be
recorded in the patient contact form and forwarded to
the research physiotherapist. The research physiotherap-
ist will telephone the patient 4 weeks after this consult-
ation to discuss any further questions and confirm if the
patient would like to participate in the study.
Consent
Informed consent will be obtained by the chief investiga-
tor or principal investigator when the patient attends for
the preoperative planning computerised tomography
(CT) scan. This is 6 weeks after the outpatient consult-
ation for agreement to TKA and 2 weeks before surgery.
It is important to the data collection scheme that pa-
tients are able to follow commands and read and inter-
pret questions via questionnaires. For those who cannot
hear, read or understand English, an interpreter will be
provided. The operating surgeon will use the preopera-
tive CT scan to create a patient-specific computer-aided
design model and create a surgical plan for executing
both MA TKA and FA TKA in all study patients.
Allocation
After informed consent has been obtained, the research
physiotherapist will randomise the patient into one of the
two groups using an online random number generator
(www.random.org). A number from 1 to 100 will be ran-
domly generated and will allocate a patient to one of the
two arms of the study: 1–50 inclusive for the control
group, 51–100 inclusive for the investigation group. The
research physiotherapist will perform the randomisation
procedure and store the designated treatment group for
each patient on a password-encrypted file on the hospital
Kayani et al. Trials (2020) 21:194 Page 3 of 10
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
computer. The operating surgeon will have this informa-
tion communicated to him on the morning of surgery.
Surgical intervention
In patients undergoing MA TKA, femoral and tibial
bone implant positioning will be used to achieve neutral
limb alignment. In the coronal plane, femoral implant
positioning will be set at 5–7 valgus in relation to the
anatomical axis of the femur. In the sagittal plane, fem-
oral component positioning will be set at 0–5° of flexion
to optimise implant positioning while preventing notch-
ing. In the axial plane, the femoral component will be
Fig. 1 Patient enrolment flow chart. CT computerised tomography, RSA radiosteriometric analysis, TKA total knee arthroplasty
Kayani et al. Trials (2020) 21:194 Page 4 of 10
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
aligned to the surgical transepicondylar axis, which is
approximately 3° externally rotated to the posterior con-
dylar axis [2,3]. The size of the femoral implant will be
selected using posterior referencing with the largest size
that does not overhang the femur, notch the anterior
femur, or overhang the mediolateral bone edges, and
avoids overstuffing the patellofemoral joint. The femoral
implant will be positioned at the centre of the mediolat-
eral cortical bone edges. In the coronal plane, tibial im-
plant position will be aligned to the tibial mechanical
axis. In the sagittal plane, tibial implant position will be
set to 0–3° of posterior tibial slope. In the axial plane,
tibial implant will be positioned at 0–5° of external rota-
tion to Akagi’s line [2,3,45]. Tibial implant size will be
selected with the largest size that does not overhang the
anteroposterior or mediolateral bone coverage. The im-
plant will be positioned in the centre between the an-
teroposterior and mediolateral cortical bone edges.
In patients undergoing FA TKA, implants will be posi-
tioned to optimise soft tissue tension through achieving
Fig. 2 Schedule of enrolment, interventions, and assessments for all study patients.Legend: CT computerised tomography, FA TKA total knee
arthroplasty with functional alignment, MA TKA total knee arthroplasty with mechanical alignment
Kayani et al. Trials (2020) 21:194 Page 5 of 10
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
balanced flexion-extension gaps and equal mediolateral
soft tissue tension by altering bone resections and im-
plant positions rather than through soft tissue releases.
This will be achieved when possible within strict align-
ment limits, and where not achievable because of the
magnitude of a fixed deformity by balancing after bone
cuts with limited soft tissue releases. The preoperative
surgical plan will be used to fix a specific point on the
tibia and the gaps balanced to restore the obliquity of
the native joint line. In the coronal plane, femoral im-
plant positioning will be modified from a starting point
of 0° to the mechanical axis to balance the extension
gap. In the sagittal plane, femoral component position-
ing will be set to optimise component sizing while avoid-
ing notching by flexing up to 5°. In the axial plane, the
femoral component will be aligned to the surgical trans-
epicondylar axis and modified by up to 3° to balance the
flexion gap. The size of the femoral implant will be se-
lected using posterior referencing with the smallest size
that does not overhang the femur, notch the anterior
femur, or overhang mediolateral bone edges, and avoids
overstuffing the patellofemoral joint. The femoral im-
plant will be positioned at the centre of the mediolateral
cortical bone edges, favouring a lateral position if neces-
sary. In the coronal plane, tibial implant position will be
aligned to the tibial mechanical axis and then modified
to balance flexion and extension gaps by up to 3° of
varus. Valgus tibial position will be avoided. In the sagit-
tal plane, tibial implant position will be set to match the
patient’s native posterior tibial slope, modified to balance
the flexion gap if necessary. In the axial plane, the tibial
implant will be positioned using Akagi’s line [2,3,45].
Tibial implant size will be selected with the largest size that
does not overhang the anteroposterior and mediolateral
bone coverage while achieving the correct rotation. The im-
plant will be positioned in the centre between the antero-
posterior and mediolateral cortical bone edges.
All operative procedures will be undertaken using the
Mako robotic arm interactive orthopaedic system (Stryker
Limited, Kalamazoo, MI, USA) under the direct supervi-
sion of one arthroplasty surgeon (FSH). The cemented
Stryker Triathlon (Stryker Navigation, Kalamazoo, MI,
USA) cruciate-retaining knee system with asymmetrical
patellar resurfacing will be used in both groups. All bone
resections, implant positioning and limb alignment will be
within regulatory approval for the Triathlon cruciate-
retaining knee system. Overall limb alignment, defined as
the sum of the femoral and tibial coronal rotations, will
range from 3° of varus to 3° of valgus.
Outcomes
All study patients will undergo review by two blinded
observers (one orthopaedic registrar and one clinical re-
search fellow) at 2 weeks, 6 weeks, 6 months, 1 year and
2 years following surgery. During these follow-up times,
predefined clinical, functional and radiological outcomes
will be recorded by these observers using case report
forms. The following outcomes will be recorded in all
study patients:
1. Accuracy of implant positioning and limb alignment
as assessed using CT scans of the knee joint
performed postoperatively at 6 weeks.
2. Operating time (minutes)
3. Time to hospital discharge (hours)
4. Analgesia requirements during inpatient admission
and postoperatively at 6 weeks, 6 months, 1 year and
2 years
5. Patient-reported outcome measures including
Forgotten Joint Score (FJS), Oxford Knee Score
(OKS), short-form health survey of 12 items (SF-
12), Knee Injury and Osteoarthritis Outcome Score
(KOOS), WOMAC, University of California at Los
Angeles score and University College Hospital func-
tional knee score preoperatively and postoperatively
at 6 weeks, 6 months, 1 year and 2 years
6. Health-related quality of life as measured using the
European Quality of Life questionnaire with five
dimensions for adults (EQ-5D) preoperatively and
postoperatively at 6 weeks, 6 months, 1 year and 2
years
7. Mobilisation distance (metres) and use of mobility
aids during inpatient admission and postoperatively
at 6 weeks, 6 months, 1 year and 2 years
8. Range of movement (degrees) in knee joint during
inpatient admission and postoperatively at 6 weeks,
6 months, 1 year and 2 years
9. Femoral and tibial implant early migration as
assessed using RSA performed postoperatively at 2
weeks, 6 weeks, 6 months, 1 year, and 2 years
10. Gait analysis performed postoperatively at 6 months
and 1 year using an instrumented treadmill with
force plates
11. Resource use and cost-effectiveness, including com-
parisons between the two treatment groups relating
to operating time, theatre efficiency, equipment and
sterilisation costs, analgesia requirements, inpatient
rehabilitation, time to discharge, outpatient follow-
up, additional imaging costs and need for further
surgery.
12. Complications
The FJS, University of California at Los Angeles knee
score, WOMAC, OKS, KOOS, SF-12 and EQ-5D are vali-
dated tools for the clinical assessment of patients after
knee arthroplasty [21,24,31]. In addition, the blinded ob-
server will record the University College Hospital func-
tional knee score to assess overall pain, function and
Kayani et al. Trials (2020) 21:194 Page 6 of 10
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
mobility. All study patients will undergo gait analysis using
an instrumented treadmill with force plates (Kistler Gait-
way, Kistler Instrument Corporation, Amherst, NY, USA)
on a level platform. Gait analysis will be performed at the
patient’s self-selected comfortable speed and maximum
speed without running. Vertical ground reaction forces
and spatiotemporal data will be obtained from force plates
built into the treadmill. RSA radiographs will be per-
formed at regular postoperative follow-up intervals to
quantify motion between the implant and host bone,
which is highly predictive of long-term implant survival
[32,40].
Blinding
All patients and clinical staff recording postoperative
study outcomes will remain blinded to the treatment
group. Study patients will be identifiable with a unique
study number. Only the research physiotherapist will
have the key to identify individual patients and their re-
spective treatment arm. Any documents related to the
study will be archived directly at the study site by the re-
search physiotherapist within a secure filing cabinet in a
locked research office. This office has swipe card access
with onsite security and 24-h closed-circuit television
surveillance. Patient data will be logged electronically
using each patient’s unique identification number with
computer software on an encrypted, password-protected
research computer.
Sample size
Using data from a previous study recording functional
outcomes, the mean WOMAC score at 2years using MA
TKA was 26 (standard deviation 22.6) and using TKA
with kinematic alignment was 15 (standard deviation 20.3)
[14]. Using a two-tailed, two-sample ttest with an effect
size of 0.35, power of 90% with significance level of 5%,
and accounting for an expected drop-out rate of 10% dur-
ing the 2-year follow-up period, the study requires 100 pa-
tients to detect a minimal clinically important difference
of 11 points in the total WOMAC score between the two
treatment groups [13].
Statistical analysis
The analysis of the per-protocol population will be con-
sidered the primary analysis. The differences between
the MA TKA and FA TKA groups will be analysed by
calculating the difference from baseline per patient, and
a two-sided confidence interval for the difference be-
tween the changes from baseline values will be calcu-
lated. This confidence interval will cover the true
difference in the percentage change from baseline with a
probability of 95%. The following statistical methods will
be employed to analyse the data: descriptive statistics,
independent ttest, paired ttest, analysis of variance,
Fisher exact test, chi-square test and graphical displays.
Assumptions of normality will be tested with the
D’Agostino test. Assumptions of homogeneity of vari-
ance will be tested with Levene’s test. If the distribu-
tional assumptions are (severely) violated, non-
parametric techniques such as the Mann–Whitney test
will be employed. In the event that FA TKA is converted
to MA TKA intraoperatively, analysis will be performed
using the intention-to-treat population and the treat-
ment actually received by the patients. Intraoperative
conversion from FA TKA to MA TKA will be docu-
mented and presented and published as part of the
study. Statistical significance is set at a Pvalue <0.05 for
all analyses and all statistical analyses will be performed
using SPSS software version 25 (SPSS Inc., Chicago, IL,
USA). The Bonferroni correction will be used to adjust
Pvalues to reduce the risk of type I error with perform-
ing multiple statistical comparisons.
Adverse events
Adverse events are defined as any untoward medical oc-
currence in a patient or study participant that does not
necessarily have a causal relationship with the procedure
involved. 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 clinical sequelae, or death.
All SAEs during the protocol treatment will be reported
directly to the sponsor using the SAE web form. The chief
investigator will also assess the SAE for severity, causality,
seriousness and expectedness using pre-existing criteria
provided by the sponsor and will inform the Data Safety
Monitoring Board (DSMB) within 3 days of the initial ob-
servation of the event. The protocol treatment period is
defined as the period from the day that the first study pa-
tient is recruited into the trial to the day that the final
study patient has completed 2 years follow-up. The chief
investigator will also inform the London-Surrey Research
Ethics Committee and local Health Research Authority
within 3 days of the SAE taking place. Safety aspects of
the study are closely monitored by the sponsor and DSMB
using unblinded data for its judgment. In cases where the
SAE arises due to a problem with the robotic device, Stry-
ker Limited will also be notified within 2 days of the event
taking place. The chief investigator will record the follow-
ing: onset date, complete description of the event, severity,
duration, action taken and outcome for each SAE. The
chief investigator will also provide regular updates of all
SAEs to the London-Surrey Research Ethics Committee,
local Health Research Authority, DSMB, and sponsor.
Data management
On-site monitoring visits shall occur throughout the
course of the clinical study by the chief investigator. The
Kayani et al. Trials (2020) 21:194 Page 7 of 10
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
chief investigator shall permit and assist the sponsor
(should they chose to monitor the study) to carry out
verification of all study forms against data in the source
documents, which shall occur as per the departmental
policy for undertaking such activities. University College
Hospital recognises that there is an obligation to archive
study-related documents at the end of the study. The
study master file will be archived at University College
London in accordance with the University College Hos-
pital Standard Operating Procedure for Archiving of In-
vestigator Site File and Pharmacy Site File. It will be
archived for a minimum of 5 years from the study end,
and for no longer than 30 years from the study end.
End-of-protocol treatment
Reasons for going off study protocol include:
1. Completion of last follow-up visit 2 years after
surgery
2. Patient non-compliance or withdrawal (the reason
for discontinuation will be recorded in the case re-
port form)
3. Intercurrent death
All patients included in this study are free to withdraw
from the study at any time without compromise to their
future treatment. On withdrawal, patients will revert to
the standard follow-up regimen for routine (non-study)
TKA at the study site. The end-of-study form will be
completed and the reason for withdrawal documented.
This form will also be completed if the patient is lost to
follow-up or dies during the course of the study. Data to
the point of discontinuation will be used for analysis.
Monitoring
The chief investigator will monitor the progress of the
clinical study in the form of monthly research meetings
for those involved in the trial. The chief investigator will
be responsible for the day-to-day monitoring and man-
agement of the study. The University College Hospital/
University College London/Joint Research Office, on be-
half of University College London as Sponsor, will moni-
tor and conduct random audits on a selection of studies
in its clinical research portfolio. Monitoring and auditing
will be conducted in accordance with the Department of
Health Research Governance Framework for Health and
Social Care (April 2005), and in accordance with the
sponsor’s monitoring and audit policies and procedures.
As per the protocol, the principal investigator will email
the sponsor twice yearly with the following information:
delegation log, adverse event log, deviation log, and any
annual progress reports sent to the Ethics Committee.
Peer review
The study protocol was reviewed by two external re-
viewers. The suggestions and recommendations for im-
provement to the study design were implemented. The
reviewers and sponsor reviewed the revised protocol
documents and confirmed that all queries and sugges-
tions had been fully addressed.
Discussion
The concept of MA TKA is to distribute load evenly
across the components to optimise implant survivorship
and balance forces through the periarticular soft tissue
envelope for proper functioning of the knee joint. How-
ever, in the majority of patients this forces the knee into
an unnatural position with altered knee kinematics
through the arc of flexion [4,6,17,18]. FA TKA aims to
restore joint line height, preserve native obliquity, and
achieve balanced flexion-extension gaps with equal med-
iolateral soft tissue tension by manipulating bone resec-
tions and fine-tuning implant positioning, which reduces
the need for soft tissue releases. To our knowledge, this
prospective randomised control trial is the first study to
compare MA TKA with FA TKA. Robotic technology
will be used in both treatment groups, which will enable
accurate execution of the preoperative surgical plan and
help preserve the double-blinded nature of this study.
Furthermore, RSA will be used to compare micromotion
and implant survivorship between the two treatment
groups. The findings of this study will enable an im-
proved understanding of the optimal alignment tech-
nique in TKA for achieving high-levels of patient
satisfaction, improving functional outcomes, increasing
implant survivorship, improving cost-effectiveness and
reducing complications.
Trial status
This is protocol version 3.0, 1 June 2018. Patient recruit-
ment started on 28 December 2018. The estimated date
for completion of recruitment is 28 December 2020. The
estimated date for completion of the final follow-up is
28 December 2012.
Supplementary information
Supplementary information accompanies this paper at https://doi.org/10.
1186/s13063-020-4123-8.
Additional file 1. Standard Protocol Items: Recommendations for
Interventional Trials (SPIRIT) 2013 checklist—recommended items to
address in a clinical trial protocol and related documents.
Abbreviations
DSMB: Data Safety Monitoring Board; EQ-5D: European Quality of Life
questionnaire with five dimensions for adults; FA: Functional alignment;
FJS: Forgotten Joint Score; KOOS: Knee Injury and Osteoarthritis Outcome
Score; MA: Mechanical alignment; OKS: Oxford Knee Score;
RSA: Radiosteriometric analysis; SAE: Serious adverse event; SF-12: Short-form
Kayani et al. Trials (2020) 21:194 Page 8 of 10
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
health survey of 12 items; TKA: Total knee arthroplasty; WOMAC: Western
Ontario and McMaster Universities Arthritis Index
Acknowledgements
None.
Sponsor
The study is sponsored by University College London, 235 Euston Road,
Bloomsbury, London, NW1 2BU, UK (reference 241404).
Authors’contributions
BK, JT and FSH performed background research, identified gaps in the
medical literature, created the study objectives, designed the trial, created
the case report forms, attended Research Ethics Committee meetings,
helped write the study protocol and prepared the National Institute for
Health Research Clinical Research Network Industry costing template. PM, SO
and SK helped write the study protocol. All authors read and approved the
final manuscript.
Funding
Funding was obtained from Stryker Limited. There are no terms or
conditions to the funding that will impact the study design, data collection,
analysis, interpretation of data, or writing the manuscript.
Availability of data and materials
The datasets used and/or analysed during the current study are available
from the corresponding author on reasonable request.
Ethics approval and consent to participate
The study has been reviewed and approved for patient recruitment by the
London-Surrey Research Ethics Committee, United Kingdom (reference 18/
LO/0783). Written informed consent will be obtained from participants dur-
ing recruitment on site and prior to data collection. Consent to use the data
collected for scientific reporting and publication will also be obtained at the
same time as the consent to participate.
Consent for publication
The findings of this research will be published in peer-reviewed journals. All
study patients will provide informed consent for publication of anonymised
patient data and study findings. Authorship will reflect the amount of time
spent designing the study, collating the data, analysing the results, and writ-
ing the manuscript.
Competing interests
FSH reports board membership of The Bone and Joint Journal and the Annals
of the Royal College of Surgeons, has acted as a consultant for Smith &
Nephew, Corin, MatOrtho and Stryker, has received payment for lectures
including service on speakers’bureaus for Smith & Nephew and Stryker, and
has received royalties paid by Smith & Nephew, MatOrtho, Corin and Stryker,
all outside the submitted work. SK reports consultancy, payment for lectures
including service on speakers’bureaus, payment for development of
education presentations and travel/accommodations/meeting expenses for
Smith & Nephew and AO, all outside the submitted work. The remaining
authors declare no competing interests.
Received: 18 December 2019 Accepted: 30 January 2020
References
1. National Joint Registry. 16th Annual Report 2019.https://reports.njrcentre.
org.uk/Portals/0/PDFdownloads/NJR%2016th%20Annual%20Report%202019.
pdf.Date accessed 22 Jan 2020.
2. Aglietti P, Sensi L, Cuomo P, et al. Rotational position of femoral and tibial
components in TKA using the femoral transepicondylar axis. Clin Orthop
Relat Res. 2008;466(11):2751–5.
3. Akagi M, Oh M, Nonaka T, et al. An anteroposterior axis of the tibia for total
knee arthroplasty. Clin Orthop Relat Res. 2004;420:213–9.
4. Almaawi AM, Hutt JRB, Masse V, et al. The impact of mechanical and
restricted kinematic alignment on knee anatomy in total knee arthroplasty.
J Arthroplast. 2017;32(7):2133–40.
5. Baker PN, van der Meulen JH, Lewsey J, et al. The role of pain and function
in determining patient satisfaction after total knee replacement. Data from
the National Joint Registry for England and Wales. J Bone Joint Surg (Br).
2007;89(7):893–900.
6. Bellemans J, Banks S, Victor J, et al. Fluoroscopic analysis of the kinematics
of deep flexion in total knee arthroplasty. Influence of posterior condylar
offset. J Bone Joint Surg (Br). 2002;84(1):50–3.
7. Bellemans J, Colyn W, Vandenneucker H, et al. The Chitranjan Ranawat
award: is neutral mechanical alignment normal for all patients? The concept
of constitutional varus. Clin Orthop Relat Res. 2012;470(1):45–53.
8. Bonner TJ, Eardley WG, Patterson P, et al. The effect of post-operative
mechanical axis alignment on the survival of primary total knee
replacements after a follow-up of 15 years. J Bone Joint Surg (Br). 2011;
93(9):1217–22.
9. Bourne RB. Measuring tools for functional outcomes in total knee
arthroplasty. Clin Orthop Relat Res. 2008;466(11):2634–8.
10. Bourne RB, Chesworth BM, Davis AM, et al. Patient satisfaction after total
knee arthroplasty: who is satisfied and who is not? Clin Orthop Relat Res.
2010;468(1):57–63.
11. Cherian JJ, Kapadia BH, Banerjee S, et al. Mechanical, anatomical, and
kinematic axis in TKA: concepts and practical applications. Curr Rev
Musculoskelet Med. 2014;7(2):89–95.
12. Choong PF, Dowsey MM, Stoney JD. Does accurate anatomical alignment
result in better function and quality of life? Comparing conventional and
computer-assisted total knee arthroplasty. J Arthroplast. 2009;24(4):560–9.
13. Clement ND, Bardgett M, Weir D, et al. What is the minimum clinically
important difference for the WOMAC index after TKA? Clin Orthop Relat Res.
2018;476(10):2005–14.
14. Dossett HG, Estrada NA, Swartz GJ, et al. A randomised controlled trial of
kinematically and mechanically aligned total knee replacements: two-year
clinical results. Bone Joint J. 2014;96-b(7):907–13.
15. Dossett HG, Swartz GJ, Estrada NA, et al. Kinematically versus mechanically
aligned total knee arthroplasty. Orthopedics. 2012;35(2):e160–9.
16. Dunbar NJ, Roche MW, Park BH, et al. Accuracy of dynamic tactile-guided
unicompartmental knee arthroplasty. J Arthroplast. 2012;27(5):803–8.e1.
17. Eckhoff D, Hogan C, DiMatteo L, et al. Difference between the epicondylar
and cylindrical axis of the knee. Clin Orthop Relat Res. 2007;461:238–44.
18. Eckhoff DG, Bach JM, Spitzer VM, et al. Three-dimensional mechanics,
kinematics, and morphology of the knee viewed in virtual reality. J Bone
Joint Surg Am. 2005;87(Suppl 2):71–80.
19. Fang DM, Ritter MA, Davis KE. Coronal alignment in total knee arthroplasty:
just how important is it? J Arthroplast. 2009;24(6 Suppl):39–43.
20. Font-Rodriguez DE, Scuderi GR, Insall JN. Survivorship of cemented total
knee arthroplasty. Clin Orthop Relat Res. 1997;345:79–86.
21. Garratt AM, Brealey S, Gillespie WJ. Patient-assessed health instruments for
the knee: a structured review. Rheumatology (Oxford). 2004;43(11):1414–23.
22. Gill GS, Joshi AB, Mills DM. Total condylar knee arthroplasty. 16- to 21-year
results. Clin Orthop Relat Res. 1999;367:210–5.
23. Gu Y, Roth JD, Howell SM, et al. How frequently do four methods for
mechanically aligning a total knee arthroplasty cause collateral ligament
imbalance and change alignment from normal in white patients? AAOS
exhibit selection. J Bone Joint Surg Am. 2014;96(12):e101.
24. Haywood KL, Garratt AM, Fitzpatrick R. Quality of life in older people: a
structured review of generic self-assessed health instruments. Qual Life Res.
2005;14(7):1651–68.
25. Hollister AM, Jatana S, Singh AK, et al. The axes of rotation of the knee. Clin
Orthop Relat Res. 1993;290:259–68.
26. Howell SM, Howell SJ, Kuznik KT, et al. Does a kinematically aligned total
knee arthroplasty restore function without failure regardless of alignment
category? Clin Orthop Relat Res. 2013;471(3):1000–7.
27. Howell SM, Papadopoulos S, Kuznik K, et al. Does varus alignment adversely
affect implant survival and function six years after kinematically aligned total
knee arthroplasty? Int Orthop. 2015;39(11):2117–24.
28. Howell SM, Papadopoulos S, Kuznik KT, et al. Accurate alignment and high
function after kinematically aligned TKA performed with generic
instruments. Knee Surg Sports Traumatol Arthrosc. 2013;21(10):2271–80.
29. Ishikawa M, Kuriyama S, Ito H, et al. Kinematic alignment produces near-normal
knee motion but increases contact stress after total knee arthroplasty: a case
study on a single implant design. Knee. 2015;22(3):206–12.
30. Jeffery RS, Morris RW, Denham RA. Coronal alignment after total knee
replacement. J Bone Joint Surg (Br). 1991;73(5):709–14.
Kayani et al. Trials (2020) 21:194 Page 9 of 10
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
31. Jenkinson C, Chandola T, Coulter A, et al. An assessment of the construct
validity of the SF-12 summary scores across ethnic groups. J Public Health
Med. 2001;23(3):187–94.
32. Karrholm J, Borssen B, Lowenhielm G, et al. Does early micromotion of
femoral stem prostheses matter? 4-7-year stereoradiographic follow-up of
84 cemented prostheses. J Bone Joint Surg (Br). 1994;76(6):912–7.
33. Matsuda S, Kawahara S, Okazaki K, et al. Postoperative alignment and ROM
affect patient satisfaction after TKA. Clin Orthop Relat Res. 2013;471(1):127–
33.
34. Matsumoto T, Takayama K, Ishida K, et al. Radiological and clinical
comparison of kinematically versus mechanically aligned total knee
arthroplasty. Bone Joint J. 2017;99-b(5):640–6.
35. Noble PC, Conditt MA, Cook KF, et al. The John Insall Award: patient
expectations affect satisfaction with total knee arthroplasty. Clin Orthop
Relat Res. 2006;452:35–43.
36. Parratte S, Pagnano MW, Trousdale RT, et al. Effect of postoperative
mechanical axis alignment on the fifteen-year survival of modern,
cemented total knee replacements. J Bone Joint Surg Am. 2010;92(12):
2143–9.
37. Ritter MA, Faris PM, Keating EM, et al. Postoperative alignment of total knee
replacement: its effect on survival. Clin Orthop Relat Res. 1994;(299):153–6.
38. Ritter MA, Lutgring JD, Davis KE, et al. The role of flexion contracture on
outcomes in primary total knee arthroplasty. J Arthroplast. 2007;22(8):1092–
6.
39. Rodricks DJ, Patil S, Pulido P, et al. Press-fit condylar design total knee
arthroplasty. Fourteen to seventeen-year follow-up. J Bone Joint Surg Am.
2007;89(1):89–95.
40. Ryd L, Albrektsson BE, Carlsson L, et al. Roentgen stereophotogrammetric
analysis as a predictor of mechanical loosening of knee prostheses. J Bone
Joint Surg (Br). 1995;77(3):377–83.
41. Schiraldi M, Bonzanini G, Chirillo D, et al. Mechanical and kinematic
alignment in total knee arthroplasty. Ann Transl Med. 2016;4(7):130.
42. Selvik G. Roentgen stereophotogrammetry. A method for the study of the
kinematics of the skeletal system. Acta Orthop Scand Suppl. 1989;232:1–51.
43. Selvik G, Alberius P, Aronson AS. A roentgen stereophotogrammetric
system. Construction, calibration and technical accuracy. Acta Radiol Diagn
(Stockh). 1983;24(4):343–52.
44. Waterson HB, Clement ND, Eyres KS, et al. The early outcome of kinematic
versus mechanical alignment in total knee arthroplasty: a prospective
randomised control trial. Bone Joint J. 2016;98-b(10):1360–8.
45. Yu HC, Wen H, Zhang Y, et al. Research on the reliability of the Akagi line as
a reference axis to guide for rotational alignment of the proximal tibial
component in total knee arthroplasty. Zhongguo Gu Shang. 2015;28(10):
884–7.
Publisher’sNote
Springer Nature remains neutral with regard to jurisdictional claims in
published maps and institutional affiliations.
Kayani et al. Trials (2020) 21:194 Page 10 of 10
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
1.
2.
3.
4.
5.
6.
Terms and Conditions
Springer Nature journal content, brought to you courtesy of Springer Nature Customer Service Center GmbH (“Springer Nature”).
Springer Nature supports a reasonable amount of sharing of research papers by authors, subscribers and authorised users (“Users”), for small-
scale personal, non-commercial use provided that all copyright, trade and service marks and other proprietary notices are maintained. By
accessing, sharing, receiving or otherwise using the Springer Nature journal content you agree to these terms of use (“Terms”). For these
purposes, Springer Nature considers academic use (by researchers and students) to be non-commercial.
These Terms are supplementary and will apply in addition to any applicable website terms and conditions, a relevant site licence or a personal
subscription. These Terms will prevail over any conflict or ambiguity with regards to the relevant terms, a site licence or a personal subscription
(to the extent of the conflict or ambiguity only). For Creative Commons-licensed articles, the terms of the Creative Commons license used will
apply.
We collect and use personal data to provide access to the Springer Nature journal content. We may also use these personal data internally within
ResearchGate and Springer Nature and as agreed share it, in an anonymised way, for purposes of tracking, analysis and reporting. We will not
otherwise disclose your personal data outside the ResearchGate or the Springer Nature group of companies unless we have your permission as
detailed in the Privacy Policy.
While Users may use the Springer Nature journal content for small scale, personal non-commercial use, it is important to note that Users may
not:
use such content for the purpose of providing other users with access on a regular or large scale basis or as a means to circumvent access
control;
use such content where to do so would be considered a criminal or statutory offence in any jurisdiction, or gives rise to civil liability, or is
otherwise unlawful;
falsely or misleadingly imply or suggest endorsement, approval , sponsorship, or association unless explicitly agreed to by Springer Nature in
writing;
use bots or other automated methods to access the content or redirect messages
override any security feature or exclusionary protocol; or
share the content in order to create substitute for Springer Nature products or services or a systematic database of Springer Nature journal
content.
In line with the restriction against commercial use, Springer Nature does not permit the creation of a product or service that creates revenue,
royalties, rent or income from our content or its inclusion as part of a paid for service or for other commercial gain. Springer Nature journal
content cannot be used for inter-library loans and librarians may not upload Springer Nature journal content on a large scale into their, or any
other, institutional repository.
These terms of use are reviewed regularly and may be amended at any time. Springer Nature is not obligated to publish any information or
content on this website and may remove it or features or functionality at our sole discretion, at any time with or without notice. Springer Nature
may revoke this licence to you at any time and remove access to any copies of the Springer Nature journal content which have been saved.
To the fullest extent permitted by law, Springer Nature makes no warranties, representations or guarantees to Users, either express or implied
with respect to the Springer nature journal content and all parties disclaim and waive any implied warranties or warranties imposed by law,
including merchantability or fitness for any particular purpose.
Please note that these rights do not automatically extend to content, data or other material published by Springer Nature that may be licensed
from third parties.
If you would like to use or distribute our Springer Nature journal content to a wider audience or on a regular basis or in any other manner not
expressly permitted by these Terms, please contact Springer Nature at
onlineservice@springernature.com
Available via license: CC BY 4.0
Content may be subject to copyright.
