Efficiency Assessment of the Methodology for the Follow-up of Patients With Knee Prostheses

Study Overview
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Brief Summary
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Total knee arthroplasty (TKA) is currently the international standard for the treatment of degenerative and rheumatological diseases of the knee joint, as well as certain types of fractures. Although TKA is a procedure that has been shown to be effective in relieving pain and improving function in patients with osteoarthritis, approximately 20% of patients are dissatisfied with the results. Traditional methods of assessing the outcome after joint arthroplasty often focus on objective indicators of surgery and neglect the needs and opinions of patients. Because of this, this research project has the aim to know the effectiveness of two models of stabilization of total knee prostheses on the functionality achieved and perceived by the patient, as well as in the knee joint biomechanics during movement in activities of daily life. On the other hand, as a secondary objective, we propose to determine prognostic biomarkers of knee prosthesis function based on radiological information, quantification of cytokines, intra-articular markers, and biomechanical functional evaluation that correlate and predict a correct evolution of patients with a knee replacement. To carry out these objectives, 80 participants will be included with an indication to perform total knee joint replacement surgery. Participants will be randomized allocated into two groups: i. participants with a prosthesis with medial condylar stabilization ii. participants with a traditional prosthesis with central pivot stabilization. Participants will be evaluated at five-times: before surgery, immediate postsurgical, at 3 months of evolution, 6 months of evolution, and one year of evolution.

Detailed Description
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I. Background Total knee arthroplasty (TKA) is currently the international standard for the treatment of degenerative and rheumatological diseases of the knee joint, as well as certain types of fractures. It is estimated that knee osteoarthritis affects 10% of the population over 55 years of age, of which one in four patients is severely disabled, which produces a social and economic cost of great magnitude in the Western countries due to the loss of working hours, the high consumption of medicines and the use of different health resources. During the last decade, the number of TKAs performed has increased considerably worldwide, surpassing the number of total hip arthroplasties (THAs). It is estimated that between 2005 and 2015, the number of knee replacements increased by 90% and that this figure will grow to 675% in 2030. In economic terms, the average cost of a primary knee replacement is € 5,000, with the cost of the implant being one of the most important factors (15-25%). In the case of a revision TKA, the implant costs are three times higher compared to a primary TKA. If we look at the figures in numbers and in the cost of this type of implant, we see that in Spain in 2017, 130 knee prostheses were implanted for every 100,000 inhabitants. Assuming that the cost of this implant ranges between € 1800 - € 2800 depending on the regions in which the surgery is carried out, we can give you an idea of the social and economic impact of the problem. Although TKA is a procedure that has been shown to be effective in relieving pain and improving function in patients with osteoarthritis, approximately 20% of patients are dissatisfied with the results. Traditional methods of assessing the outcome after joint arthroplasty often focus on objective indicators of surgery and neglect the needs and opinions of patients. However, the concerns of patients after TKA can differ significantly from those of their surgeons. Consequently, the need for postoperative evaluation to use tools to assess patient-relevant outcomes and provide a more patient-centered view of the outcome of their treatment has been increasingly recognized. The data reviewed show the importance, on the one hand, of prosthetic designs that guarantee optimal functioning and patient satisfaction and, on the other, of tools for the clinical follow-up of patients that ensure the early detection of complications and an efficient strategy. rehabilitation, in order to avoid or delay the need for revision surgery. Assessment tools are especially necessary during the first year after the intervention, a period in which there is a significant percentage of patients who present early complications that can lead to revision surgery. In relation to prosthetic elements, with the aim of improving functional results and patient satisfaction, a new concept of stabilization of knee prostheses has emerged, this being an adaptation of the concept of condylar prostheses with medial condylar stabilization (such as the GMK Sphere prosthesis marketed by MEDACTA). Supposedly, it offers better kinematic behavior to the implant and also greater functional satisfaction compared to traditional prostheses with stabilization by means of a central pivot (such as the PERSONA prosthesis, commercialized by the company ZIMMER-BIOMET, among other models). On the other hand, in relation to post-surgery patient monitoring, progress is currently being made in the continuous monitoring of patients through objective and subjective clinical indicators, as well as information from mobile devices that could serve as triage for identify situations with a poor prognosis, verify compliance with the indications related to physiotherapy and achieve better performance of complementary tests. However, there is a lack of studies that corroborate its prognostic capacity on the survival and function of knee prostheses. II. Objectives and Hypothesis Due to the information reviewed, this research project has the following aims: To aim to know the effectiveness of two models of stabilization of total knee prostheses on the functionality achieved and perceived by the patient, as well as in the knee joint biomechanics during movement in activities of daily life. On the other hand, as a secondary objective, we propose to determine prognostic biomarkers of knee prosthesis function based on radiological information, quantification of cytokines, intra-articular markers, and biomechanical functional evaluation that correlate and predict a correct evolution of patients with knee replacement. Thanks to the global analysis of this information, these biomarkers will make it possible to identify the patients with the highest risk, the causes of failure, and the set of tests to be carried out that can foresee a foreseeable failure early on in order to make preventive decisions, adapt the treatment and increase the success rates of the same. Our research hypothesis proposes that the development of prognostic biomarkers of knee prosthesis function based on clinical and radiological information, quantification of serum and intra-articular markers, health questionnaires, and biomechanical functional evaluation allows to prevent the failure of prosthetic functioning and ensure the effectiveness of the knee implant regardless of the surgical technique used. III. General procedures This study will be carried out at the Hospital Clínico Universitario de Valencia with the INCLIVA Health Research Institute and the University of Valencia (Spain). The Hospital Clínico Universitario de Valencia has extensive experience in joint reconstructive surgery. Around 225-250 knee prostheses are implanted annually at this Center, having incorporated the different technical variants of the surgical procedure. All the medical services involved in the treatment and control of the implantation of total knee prostheses participate in this project: the Orthopedic Surgery and Traumatology Service, the Rehabilitation and Physical Medicine Service, the Diagnostic Imaging Service, and the Clinical Analysis Service. Further, In addition, the project will have the collaboration of the Research group on Personal Autonomy, Dependence and Serious Mental Disorders of the INCLIVA Institute, which has a Biomechanical Assessment Laboratory that will be used to perform functional assessments on patients. IV. Methodology IV.1. Study design The study design is a double-blind, Randomized Control Trial (RCT) with 1-years follow-up and a convenience sample (specifically, modal instance sampling) in two parallel-group. IV.2 Participants The inclusion criteria for participants are: 1) women and men with an age range between 50 and 85 years, 2) to have an indication for the use of a primary total knee prosthesis with patella fitting, 3) to have the ability to get involved in the basal measurement sessions and understand the information provided by the evaluator, and 4) to present good general health status. On the other hand, the exclusion criteria for participating in this study are considered: 1) to be a carrier of a prosthesis in other joints of the lower limb, 2) to be a carrier of a unicompartmental prosthesis, 3) to present previous knee fracture, 4) to present a previous intervention of lumbar spine or stenosis of diagnosed canal, 5) to present previous intervention of the hip, tibia or femur, 6) to have disabling painful pathology in the contralateral lower limb, 7) to have recorded in their medical history the existence of a lower limb length asymmetry greater than 2 cm or, be wearing a shoe lift, 8) to have antecedents of neurological or orthopedic injury that may influence the ability to walk, (e.g. stroke), 9) being diagnosed with rheumatoid arthritis or another type of arthritis that affects other joints of disabling lower limb, 10) to present morbid obesity (BMI> 39), 11) to be in a situation of moderate or high dependence, 12) to present severe cognitive impairment , 13) to develop post-surgical complications such as infection, deep vein thrombosis, arthrofibrosis and periprosthetic fracture. IV.3 Assessment and outcomes The study participants will be evaluated in five periods of evolution: before surgery, immediately after surgery, at 3 months of evolution, at 6 months of evolution and a year after having performed the surgery. The set of tests to be carried out in each evaluation time and the data to be recorded are the following: Clinical data: Age (years), Sex (men/women), Gender, BMI (kg/m2), race, level of education, marital status, height, weight, number of chronic diseases besides osteoarthritis, length of inferior extremities measured weight-bearing from the anterior iliac spine (AIS) to the medial malleolus, % of body fat, % of body water. Chronicity of knee symptoms; Diagnosis, Surgical approach, Prosthetic implant, Side of surgery, Days of hospital stay, Leg swelling evaluation with thigh and calf circumference, Hospital readmission, Post-cx complications, Fall Incidence. Blood pressure Assessment scales: Pain: it will be used the numeric rating scale to assess knee pain, and with the Kujula knee score. Functional status of the knee / Physical function: it will be used the Preoperative new Knee Society Score, The Oxford Knee Score (OKS) questionnaire, the Knee Osteoarthritis Outcome Score, The Western Ontario and McMaster Universities Osteoarthritis Index, The Canadian Occupational Performance Measure, and the Knee Outcome Survey Activities of Daily Living Scale. Health status: it will be used the Short Form 36 (SF-36). Quality of life: it will be used the Hospital for Special Surgery Scale, and the EuroQol Group 5-dimensions-Level 5 Personal perception and mental status: it will be used the Forgotten Joint Score, Readiness for Discharge scale, the Beck Depression Inventory Scale, and for assessing the anxiety it will be used the Beck Anxiety Inventory Scale. Cognitive status: it will perform a cognitive screening by the Screen for Cognitive Impairment in Psychiatry (SCIP). In addition, it will be used the Wechsler Intelligence Scale for Adults (WAIS-III) and the Functional Assessment Short Test. Complementary test: Imaging tests by radiography on the operated knee Lower limb telemetry. Carrying out computed tomography in cases of inadequate function, to identify possible causes, without subjecting the patients to excessive irradiation. Determination of Serum Levels of inflammatory biomarkers status: Interleukin-6, procalcitonin, calprotectin, and C-reactive protein. Determination of intra-joint biomarkers: C-reactive protein, and alpha-defensin. Biomechanical assessment: Range of motion in both knees. Strength of the operated and contralateral knee flexor and extensor muscles: maximum voluntary isometric strength and voluntary muscle activation. Balance assessment with dynamometric platform during bipedal position and functional test. Kinematic assessment of the lower limb with a 3D-photogrammetry system and muscle activity measured with surface electromyography during gait, bending and stooping, up and downstairs, sit to stand test. Gripping force of the hand as an indicator of physical frailty. IV.4 Intervention Participants will be randomized allocated into two groups: i. participants with a prosthesis with medial condylar stabilization ii. participants with a traditional prosthesis with central pivot stabilization. IV.5 Sample size, recruitment, and randomization To respond to the main objective of the study, a total of 82 people will be recruited. This sample size has been determined using the G * Power v. 3.1, based on the expected differences between the two subject groups from baseline to 3-month follow-up [21], with a small-medium effect (f = 0.15), a statistical significance of 5% at the two-tailed level, and a power of 90%. If 20% of possible dropouts are also considered during the study, the initial recruitment should be 99 people. Patients will be recruited from the Orthopedic Surgery and Traumatology Service of Valencia University Clinical Hospital (Spain) only. From the beginning of the study, every week the coordinating researcher and head of the Orthopedic Surgery and Traumatology Service, will review the scheduled surgeries of the following weeks to ask each patient with scheduled TKA if they are interested in participating. All patients who show interest will be informed and the criteria for participation in their usual pre-surgical trauma appointment will be evaluated. The study recruitment period will remain open for one year. Due to patient recruitment will occur over a prolonged period of time, the assignment to the groups will be performed as block randomization with a 1:1 allocation. This restrictive sample randomization or permuted block randomization would allow us to ensure a periodic balance in the number of participants assigned to each intervention group. For this, 13 different blocks were created among themselves, with a homogeneous distribution (8) of letters A and B, representing each of the prosthetic options. These 13 blocks were randomly ordered to assign each participant according to the blocks. The coordinating researcher of the project was the only member who knew about the randomization sequence and is the one who will indicate to the two surgeons in the study what type of surgery to do according to the randomized sequence. There not considered stratification factors in randomization. Regarding the blinding of the study, both the study patients and the researcher who performing the statistical analyzes will be unaware of the type of prosthetic stabilization used. The two surgeons in the study and the evaluators of the outcomes will know the type of prosthesis used in each patient.

Official Title
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Efficiency Assessment of the Methodology for the Follow-up of Patients With Knee Prostheses

Conditions
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Total Knee Arthroplasty

Intervention / Treatment
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* Procedure: Total knee prosthesis with medial condylar stabilization
* Procedure: Total knee prosthesis with central pivot stabilization


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women and men with an age range between 50 and 85 years Being on the waiting list in the Traumatology service of the Hospital Clínico Universitario de Valencia for surgical intervention and implantation of a knee prosthesis To have an indication for the use of a primary total knee prosthesis with patella fitting To have the ability to get involved in the measurement sessions and understand the information provided by the evaluator, and To present good general health status. Exclusion Criteria: To be a carrier of a prosthesis in other joints of the lower limb To be a carrier of a unicompartment prosthesis To present previous knee fracture To present a previous intervention of lumbar spine or stenosis of diagnosed canal To present previous intervention of the hip, tibia or femur To have disabling painful pathology in the contralateral lower limbç To have recorded in their medical history the existence of a lower limb length asymmetry greater than 2 cm or, be wearing a shoe lif To have antecedents of neurological or orthopedic injury that may influence the ability to walk, (e.g. stroke) Being diagnosed with rheumatoid arthritis or another type of arthritis that affects other joints of disabling lower limb To present morbid obesity (BMI> 39) To be in a situation of moderate or high dependence To present severe cognitive impairment To develop post-surgical complications such as infection, deep vein thrombosis, arthrofibrosis, and periprosthetic fracture.

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Total knee prosthesis 1<br>prosthesis with medial condylar stabilization | Procedure: Total knee prosthesis with medial condylar stabilization<br>* Surgery will be done of Total knee prosthesis with medial condylar stabilization<br>|
| Active Comparator: Total knee prosthesis 2<br>traditional prosthesis with central pivot stabilization | Procedure: Total knee prosthesis with central pivot stabilization<br>* Surgery will be done of Total knee prosthesis with central pivot stabilization<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum walking speed (MWS) | Maximum distance traveled by the body per unit of time (m·s-1). It will ask for participants to walk safely and as quickly as possible, without running, in a 10 m, straight and flat walkway. The two first and last stride will be discarded from the analysis in order to avoid the acceleration and deceleration of the star and end of the gait. The gait speed will be measured with the NedAMH/IBV v5.6 (Institute of Biomechanics of Valencia, Spain) software which uses two infrared or red light photocells to measured gait speed. This outcome will be measured in all the assessment times of the study. | 1 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Total knee arthroplasty, Functional assessment, Prognosis biomarkers, Medial condylar stabilization, Central pivot stabilization