Clinical evaluation of Signature Personalized Patient Care
Prospective, clinical, multicentre, randomised, double blind study

Signature* Personalized Patient Care (Biomet) is a recently introduced product
for alignment of the knee during TKA for placement of the Vanguard* Complete
Knee System. This new patient-specific guide is an extramedular instrument that
makes intramedullar alignment unnecessary. Signature* will be created from a
Magnetic Resonance Imaging scan (MRI). Using software (Materialise, Leuven,
Belgium), the MRI scan will be segmented and assembled into a 3-Dimensional
model. The Signature* alignment guide will be created for both the femur
(Figure 1), that allows the surgeon to place pins for the distal cut block and
drill holes for the 4-in-1 block, and the tibia (Figure 2) that allows the
surgeon to place the pins for the tibial resection block.
With Signature* it is possible to plan the total knee replacement, the position
and size of the prosthesis accurately prior to surgery.
Lombardi et all. tried to find out if Signature* was applicable to assist as an
alignment guide during TKA. They analysed 52 knees aligned with Signature*.
They found that operation time was 10 minutes shorter (77 vs. 87 minutes;
P=.03) for the second 26 TKA, compared to the first 26 TKA. perioperative blood
loss was low (averaged 52cc with a range of 45-100cc) and there were no
complications intraoperatively. Also was found that the Knee Society Score,
pre-operative compared with post-operative was improved (KSS-pain: 8 to 38,
P<.0001; KSS-function: 58.1 to 64.1, P=NS) 19.
First, Signature* placement is expected to be at least as precise as with
conventional intramedullary guiding because computer software is used to
determine the correct position of the prosthesis. Therefore, the survival of
the prosthesis is expected to be better because of less polyethylene wear in
the long term.
Second, the Signature* surgical procedure is expected to result in a slightly
reduced blood loss and a lower thromboembolic complication rate, compared to
conventional intramedullary guiding because no entrance into the medullary
cavity of the bone needs te be made.
Third, this method for alignment of the knee is expected to result in shorter
surgical operation time because it is less invasive and less surgical
instruments are needed.
However, no additional studies to the study of Lombardi et al. have yet been
conducted on the Signature alignment guide sofare. Therefore, the aims of this
study are: to prove that the new device, Signature* Personal Patient Care for
Total Knee Arthroplasty, is at least as effective in clinical outcome as the
widely used current method for total knee arthroplasty, the conventional
Vanguard CR cemented fixation, and results in placement that is at least as
precise as with the conventional method.

Primary objectives
* To evaluate the initial and long-term clinical results in terms of function,
quality of life and pain/satisfaction of the Signature* procedure compared to
the standard operation instruments (Vanguard CR cemented fixation).
* To evaluate the alignment of the Signature* procedure compared to the
standard operation instruments (Vanguard CR cemented fixation).

Secondary objectives
* To evaluate the efficacy of the Signature* procedure in terms of operation
time, bloodloss and length of hospital stay compared to the standard operation
instruments (Vanguard CR cemented fixation).
* To evaluate the safety of the Signature* procedure in terms of
complications/adverse events and needed change of plans compared to the
standard operation instruments compared to the standard operation instruments
(Vanguard CR cemented fixation).
* To evaluate the survival and wear rate of the polyethylene insert of the
Signature* alignment guide compared to the standard operation instruments
(Vanguard CR cemented fixation).
* To evaluate the cost-effectiveness of the Signature* procedure compared to
the standard operation instruments (Vanguard CR cemented fixation).

Prospective, multicenter, randomised, double-blind, controlled trial.
Two Dutch hospitals participating:
* Orbis Medical Park, Sittard, the Netherlands.
* St. Anna Hospital, Geldrop, the Netherlands.

Patients will be randomized to be operated on with the use of the conventional
alignment method (control group), or Signature* Personalized Patient Care
(trial group). Patients have an equal opportunity of being assigned to the
trial group or control group. The randomization will occur via a random number
generator. The surgeon or clinical researcher does not choose the participants
for each group. The patients are stratified to hospital, meaning that in each
hospital half of the patients will obtain the trial implant.
The patients are not informed on the type of prosthesis that is being placed.
The outcome assessor is blinded to the treatment allocation of the patients.

Biomet Signature* Personalized Patient Care
Signature* Personalized Patient Care utilizes patient specific femoral and
tibial positioning guides, developed from MRI. The guides are made of polyamide
and are disposable.
The Signature* system, which fits the femoral and tibial components
independently, is used with the Vanguard* Complete Knee System. This prosthesis
is designed for achieving 145 degrees of flexion and has a broad range of
available implant sizes.

Risks are those associated with placement of the Vanguard* Complete Knee
System.
Theoretical disadvantage of the use of the Signature* alignment guide is the
possible occurrence of allergic reactions. Preliminary to surgery (6 weeks),
the patient will undergo a MRI-scan of hip, knee and ankle.
All patients will obtain the standard rehabilitation protocol. During the
standaard outpatient visits (pre-operatively, 6 weeks, 3 months, 1 year, 2
years, 5 years and 10 years) standard questionnaires (applying also to
non-study patients) concerning knee function and pain will be taken.
Additionally, standing, weight-bearing long-leg X-rays will be made instead of
standard X-rays in non-study patients.
The clinical results of the Signature knee are unknown, however, they are
expected to be equal to the conventional total knee arthroplasty.
Operation time is expected to be shorter with the use of the Signature*
alignment guide but has not yet been proven in clinical trials.
Blood loss is expected to be less with Signature total knee arthroplasty but
has not yet been proven in clinical trials.
Signature total knee arthroplasty is expected to give a longer survival,
however, this is not clinically confirmed.