A Comparison of the Persona Total Knee Arthroplasty System Using CR or MC Polyethylene

Knee replacement is an established treatment for late stage osteoarthritis (OA) of the knee (Charnley et al. 1961). Recently, Zimmer-Biomet have introduced Persona Total Knee system with design changes that include asymmetric tibia plate, increased medial pivoting and more extensive choices in respect to poly thickness, all with the purpose to improve balancing, stability and longevity. One design change that is introduced is the medial congruent (MC) polyethylene to be used instead of standard cruciate retaining (CR) design. The theoretic proposed benefit of MC polyethylene bearing is improved kinematics mimicking native knee motion. However, currently no studies exist evaluating outcome following use of MC polyethylene bearing. Therefore such design changes and proposed benefits need to be evaluated in a prospective clinical trail, with focus on patient safety, satisfaction and implant durability.

In this project the investigators wish to:

Evaluate stability and fixation, intra-operative and postop complications, survivorship and patient reported outcome measures following primary total knee replacement using MC polyethylene bearing compared to CR polyethylene bearing with Persona Total Knee for treatment of knee osteoarthritis.

This project is carried out as a 2-arm randomized controlled single-blinded trial, in which the clinical and radiological outcomes after treatment of knee osteoarthritis with insertion of either 1) Persona Total Knee System with MC polyethylene bearing or 2) Persona Total Knee System with CR polyethylene bearing are compared. Recruitment of participants to this project is expected to begin in October 2016 or as soon as permission from the Regional Ethics Committee and the Danish Data Protections Agency is obtained. A total of 60 participants are to be included at Hvidovre University Hospital. Recruitment is expected completed after a period of 1.5 year. The project is expected to be completed 2 years after recruitment of the last participant (2019).

Participants are seen on an outpatient basis at 3 months, 1 and 2 years postoperatively. RSA is performed postoperatively and at all outpatient follow-ups. Dynamic RSA is performed at 1 year follow-up. The patients will be followed for survival through The Danish Knee Arthroplasty Registry.

This project is financed by Zimmer-Biomet®, Warsaw, Indiana, USA. The primary investigator of this project has independently initiated the project.

Background Knee replacement is an established treatment for late stage osteoarthritis (OA) of the knee (Charnley et al. 1961). There are different approaches to prosthetic replacement and current practices and designs are often based on limited evidence (Plate et al. 2012). There have been individual cohort studies, indirect comparisons and retrospective studies to test the efficacy of a variety of different total knee replacement devices but there are very few high quality investigations of new paradigms or significant design change. Those studies that do exist have usually been undertaken to address a combination of design changes and many involve only short-term assessments (Mäkelä et al. 2008). Ongoing research and development programs for knee replacement are increasingly taking account of the needs of the changing characteristics of the late stage OA knee population.

There is an increasing demand for joint replacement in a younger population (Mäkelä et al. 2014). Due to the changing demographics of joint replacement, the population of younger patients are seeking options that not only correct their disease or deformity, but do not limit them in activity (Geerdink et al. 2009). Activities of daily living take higher priority in this patient group, and patients needing total joint replacement do not have many options that accommodate higher levels of activity.

Studies have shown that modern implant designs can potentially improve outcome. Therefore new implants are introduced to the marked with the theoretical benefit of improved implant survival and superior patient reported outcomes. Within Total knee arthroplasty, design changes are introduced in attempt to improve knee kinematics, improve alignment and functionality, but those potential improvements need to be evaluated Recently, Zimmer-Biomet have introduced Persona Total Knee system with design changes that include asymmetric tibia plate, increased medial pivoting and more extensive choices in respect to poly thickness, all with the purpose to improve balancing, stability and longevity. One design change that is introduced is the medial congruent (MC) polyethylene to be used instead of standard cruciate retaining (CR) design. The theoretic proposed benefit of MC polyethylene bearing is improved kinematics mimicking native knee motion. However, currently no studies exist evaluating outcome following use of MC polyethylene bearing. Therefore such design changes and proposed benefits need to be evaluated in a prospective clinical trail, with focus on patient safety, satisfaction and implant durability.

The purpose of the proposed Randomized Clinical Trial (RCT) is to evaluate the outcome and safety of a newly designed polyethylene bearing by comparing it with a control group of patients implanted with an established polyethylene bearing.

Device description

The devices to be used in this project are:

The Zimmer-Biomet Persona Total Knee System

The Zimmer-Biomet Persona Total Knee System is a novel total knee system developed by Zimmer-Biomet. Components are available in numerous designs for both systems, with cemented as well as cementless fixations and with numerous polyethylene inserts to accommodate the surgical demand based on patient characteristics. Both MC polyethylene bearing and CR polyethylene bearing will be used in this study.

Femoral component:

Only cemented femoral components will be used for this study. Both standard as well as narrow femoral components will be used, depending on the patient anatomy.

Tibial component:

Only cemented tibial components will be used for this study.

Polyethylene materials:

Conventional polyethylene will be used for patients \>65 years old and Vitamine-E infused poly insert for patients ≤ 65 years old.

All devises are European Conformity (CE) marked and used as intended by the manufacturer.

Project design Project type This project is carried out as a 2-arm randomized controlled single-blinded trial, in which the clinical and radiological outcomes after treatment of hip osteoarthritis with insertion of either 1) Persona Total Knee System with MC polyethylene bearing or 2) Persona Total Knee System with CR polyethylene bearing. Allocation of the participants to one of the two treatment groups is done intraoperatively. Non-transparent envelopes are used for the randomization process. Participants are unaware of which prosthesis they receive and the research coordinator handling the collected questionnaires postoperatively is also unaware of which prosthesis the participant has received. The research assistant handling both standard RSA as well as dynamic RSA analysis is also unaware of which prosthesis the participant has received

Standard treatment Patients who decline to participate in the study as well as patients who are not included or excluded from the study will be treated with a standard Total Knee Arthroplasty (TKA) implant and standard surgical care. Persona Total Knee System with a CR polyethylene liner has been used as a standard implant of choice at Hvidovre Hospital since January 2016 for patients suited for a CR implant. Patients with insufficient posterior cruciate ligament (PCL) and other patients unsuited for a CR implant receive a posterior stabilized (LPS) NexGen TKA. All knees are performed in a standardized fast-track setup with the same surgical technique as described below, immediate mobilization after surgery and clinical and radiological controls after 3 months, 1 and 2 years.

Time schedule Recruitment of participants to this project is expected to begin in October 2016 or as soon as permission from the Regional Ethics Committee and the Danish Data Protections Agency is obtained. A total of 60 participants are to be included at Hvidovre University Hospital. Recruitment is expected completed after a period of 1 year. The project is expected to be completed 2 years after recruitment of the last participant (2019).

Participant termination It is recognized that the subject's participation in this study is entirely voluntary, and that she/he may refuse to participate and may withdraw from participation at any time without jeopardy to any future medical care. It is also recognized that the investigator, at his/her discretion, may withdraw a subject from this study based upon his/her professional judgment, e.g. in the event of deep infection leading to replacement of the prosthesis or long-term immobilization because of comorbidity. If a participant is withdrawn or rescinds their consent, a "Lost to Follow-up" case report form will be completed detailing the reason for the participant's withdrawal.

Data recording Data relevant for this project will be registered in a data sheet. An individual data sheet will be kept for each recruited participant. Data will also be aggregated and stored electronically. The storage of data will be done according to the rules posted by the Danish Data Protection Agency. This project will be notified to and approved by the Danish Data Protection Agency before recruitment of participants is initiated.

Participant population in Denmark Study population will consist of 60 participants with knee osteoarthritis set to receive primary total knee arthroplasty. The participants will be included at Hvidovre University Hospital, (see participating centers).

Number of participants Patients at are randomized to receive either 1) Persona Total Knee System with MC polyethylene bearing or 2) Persona Total Knee System with CR polyethylene bearing. Participants may be excluded intraoperatively if the PCL is found insufficient and LPS prosthesis is required.

In this 2-arm randomized controlled study the primary endpoint is implant migration measured by RSA. Secondary outcomes are: Oxford Knee Score (OKS), Oxford Knee Score -Activity \& Participation Questionnaire (APQ), anchoring questions, EQ-5D, Forgotten Joint Score and knee motion measured using dynamic RSA.

The study's primary outcome measure is implant migration measured by RSA. If the minimally relevant total migration of the prosthesis measured by RSA is set to 0.2 mm then a total of 18 participants must be enrolled in each study group to show a statistically significant difference (95 % confidence, 80 % power). In this study 2 x 30 participants are included. This will insure sufficient statistical power despite intraoperative exclusion and dropout of 40% at last follow-up and .

The power calculation is based on reaching sufficient power when a comparison of the two study groups is carried out.

Participant inclusion All participants will receive oral and written information about the project before consent. It is the responsibility of the primary investigator that the information to the participant is adequate. Participants are included when signed consent from the participant is obtained. Project information is then given in an undisturbed environment (in a closed examination room) by an authorized investigator of this project. Project information is given at the first outpatient consultation, when treatment with insertion of a TKA is decided. A nurse is present when the information is given. Participants are informed about the right to having a dependent present when project information is given. Participants are informed that a period of consideration of at least 2 weeks is an opportunity along with the right to a second consultation. Signed consent, however, is to be given latest at admittance before surgery.

The oral information is in accordance with the written information and is adjusted to the age, educational level and social conditions of the participant. It is ensured that the participant has understood the content of both the oral and written information before signed consent is given.

It is recognized that the subject's participation in this study is entirely voluntary, and that she/he may refuse to participate and may withdraw from participation at any time without jeopardy to any future medical care. It is also recognized that the investigator, at his/her discretion, may withdraw a subject from this study based upon his/her professional judgment, e.g. in the event of deep infection leading to replacement of the prosthesis or long-term immobilization because of comorbidity. If a participant is withdrawn or rescinds their consent, a "Lost to Follow-up" case report form will be completed detailing the reason for the participant's withdrawal.

Data recordings Participants in this project are identified with an assigned allocation number. At the end of the project all patient related data are destroyed.

All sensitive personal data regarding participants will be stored in accordance with guidelines presented by the Personal Data Act. Personal data regarding participants will be treated anonymously. The project will be reported to the Danish Data Protection Agency. The primary investigator will process all data. Participants will receive oral and written information concerning the handling of sensitive personal data.

Statistics A professional statistical software package will be used when processing data in this project. Comparative statistics will be used based on the distribution of data.

Publications The results of this project are expected published in an international medical journal. The results of this project are also expected presented at national and international orthopedic conventions. If publication is not achieved, the results of this project (positive, negative or inconclusive) will be presented on the homepage of the investigator's institution.

Co-authorship is awarded according to the Vancouver rules.

Eligibility Criteria:
Inclusion Criteria:

* Clinical and radiological osteoarthritis of the knee set to receive a primary unilateral total knee replacement
* \>18 years of age
* Participants must be able to speak and understand Danish
* Participants must be able to give informed consent and be cognitively intact
* Participants must be able to complete all post-operative controls
* Participants must not have severe comorbidities, American Society of Anesthesiologists Physical Status Classification System (ASA) score ≤ 3
* Clinically suitable to receive a Cruciate Retaining (CR) implant (no severe deformity and/or ligament instability)

Exclusion Criteria:

* Age under 18 years.
* Terminal illness
* Revision knee replacement surgery
* Rheumatoid Arthritis
* Traumatic etiology
* Prior surgery on the affected knee that includes osteosynthesis, anterior cruciate ligament (ACL) and/or posterior cruciate ligament (PCL) and/or collateral ligament surgery. Arthroscopy with meniscectomy / cartilage surgery / house cleaning is allowed.
* Altered pain perception and / or neurologic affection due to diabetes or other disorders.
* Patients will be excluded intraoperative if CR implant is not suitable.