Structured Treatment of Osteoarthritis of the Knee With or Without Total Knee Replacement

Study Overview
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Brief Summary
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The purpose of this study is to test whether surgical insertion of total knee replacement provides further improvement in quality of life, pain and function in addition to an algorithm for systematic non-surgical treatment consisting of corrective insoles, neuromuscular training, weight loss, patient education and pharmacological treatment with paracetamol, NSAIDs and Pantoprazol in patients with knee OA, collectively called the MEDIC-treatment(Medicine Exercise Diet Insoles Cognitive). The H1-hypothesis is that surgery with insertion of TKR in addition to the MEDIC-treatment results in a greater increase in quality of life and functional capacity and greater reduction in pain than the MEDIC- treatment alone at the primary endpoint, which is follow-up 12months after the start of the treatment. See statistical analysis plan available under Links for further description of the study.

Detailed Description
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Knee osteoarthritis (OA) is the degenerative joint disease that most often requires treatment and at the same time the one associated with the greatest social costs. In addition, the disease has many personal costs and is greatly contributing to reduced functionality and autonomy of older adults. It is recommended both nationally and internationally that the treatment of knee OA should include multiple treatment modalities. Clinical guidelines recommend that exercise, weight loss and patient education is the first step in treatment and that insoles and pharmacological treatment can be included as a supplement. If this non-surgical treatment is ineffective surgical treatment, especially surgery with insertion of total knee replacement (TKR), may be indicated. There are effects of both non-surgical treatment and TKR, but no studies exist, which examine the effect of surgery with insertion of TKR in addition to the recommended non-surgical treatment of knee OA.

Official Title
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Structured Treatment of Osteoarthritis of the Knee With or Without Total Knee Replacement. A Randomized Controlled Trial of Pain, Physical Function and Quality of Life With 12months Follow-up

Conditions
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Osteoarthritis of the Knee

Intervention / Treatment
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* Other: Neuromuscular training (NEMEX-TJR)
* Drug: Paracetamol
* Drug: Burana
* Drug: Pantoprazol
* Behavioral: Dietary counseling
* Behavioral: Patient education
* Procedure: TKR
* Other: Insoles


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Knee-OA detected by x-ray (Kellgren & Lawrence grade 2 or greater) Considered a candidate for TKR by the orthopedic surgeon. The participant is > 18 years of age. The participant can provide relevant and adequate, informed consent. Exclusion Criteria: Bilateral simultaneous TKR Revision of prior TKR, unicompartmental knee arthroplasty or high tibial osteotomy Rheumatoid arthritis Mean VAS > 60mm on a 0-100mm scale Investigator considers that the mental condition of the participant does not allow participation. The participant must not be pregnant or plan pregnancy during the study. Inability to comply with the protocol;. Inadequacy in written and spoken Danish.
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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: MEDIC<br>Medicine, Exercise, Diet, Insole and Cognitive/patient education (MEDIC) for three months. | Other: Neuromuscular training (NEMEX-TJR)<br>* 60min. of neuromuscular training two times a week for 3 months (12 weeks) using the neuromuscular training program called NEMEX-TJR.<br>* Other names: no other names;Drug: Paracetamol<br>* 1 g x 4/day<br>* Other names: no other names;Drug: Burana<br>* 400 mg x 3/day for three weeks<br>* Other names: NSAIDs are chosen in collaboration with the participant.;Drug: Pantoprazol<br>* 20mg x 1/day for three weeks<br>* Other names: no other names;Behavioral: Dietary counseling<br>* For participants with a BMI equal to or >25. The dietitian initiates a 3-month intervention that provides instruction and guidance in relation to diet and plans the number of visits according to the individual participant needs.<br>* Other names: no other names;Behavioral: Patient education<br>* The aim is to strengthen the participant's involvement in the treatment, so the participant will be in a position to handle, master and act reasonable in relation to their knee OA. This aspect of the intervention is based on principles from The Chronic Disease Self-Management Program, Lær at leve med kronisk sygdom (Learn to live with chronic illness) by The National Board of Health, Denmark and Artrosskolan Spenshult in Sweden.<br>* Other names: no other names;Other: Insoles<br>* The position of the knee is assessed using Single Leg Mini Squat. On the basis of this test it is decided which of two types of insoles (Formthotics System) the participant should have (neutral with a lateral wedge or neutral). The participants will be advised to use the insoles in all shoes.<br>* Other names: no other names;|
| Active Comparator: MEDIC + TKR<br>Medicine, Exercise, Diet, Insole and Cognitive/patient education (MEDIC) for three months after a total knee replacement. | Other: Neuromuscular training (NEMEX-TJR)<br>* 60min. of neuromuscular training two times a week for 3 months (12 weeks) using the neuromuscular training program called NEMEX-TJR.<br>* Other names: no other names;Drug: Paracetamol<br>* 1 g x 4/day<br>* Other names: no other names;Drug: Burana<br>* 400 mg x 3/day for three weeks<br>* Other names: NSAIDs are chosen in collaboration with the participant.;Drug: Pantoprazol<br>* 20mg x 1/day for three weeks<br>* Other names: no other names;Behavioral: Dietary counseling<br>* For participants with a BMI equal to or >25. The dietitian initiates a 3-month intervention that provides instruction and guidance in relation to diet and plans the number of visits according to the individual participant needs.<br>* Other names: no other names;Behavioral: Patient education<br>* The aim is to strengthen the participant's involvement in the treatment, so the participant will be in a position to handle, master and act reasonable in relation to their knee OA. This aspect of the intervention is based on principles from The Chronic Disease Self-Management Program, Lær at leve med kronisk sygdom (Learn to live with chronic illness) by The National Board of Health, Denmark and Artrosskolan Spenshult in Sweden.<br>* Other names: no other names;Procedure: TKR<br>* Surgical treatment with insertion of total knee replacement following standard procedures.<br>* Other names: Knee arthroplasty;Other: Insoles<br>* The position of the knee is assessed using Single Leg Mini Squat. On the basis of this test it is decided which of two types of insoles (Formthotics System) the participant should have (neutral with a lateral wedge or neutral). The participants will be advised to use the insoles in all shoes.<br>* Other names: no other names;|
| Active Comparator: Observational Cohort<br>If the patient can be included, but doesn't want to participate in the randomization, the patient is offered to enter into a prospective observational cohort with the same endpoints and the same follow-up as in the randomized study. The participant can then, in consultation with his/her physician, choose whether they would like MEDIC-treatment or TKR in combination with MEDIC-treatment. | Other: Neuromuscular training (NEMEX-TJR)<br>* 60min. of neuromuscular training two times a week for 3 months (12 weeks) using the neuromuscular training program called NEMEX-TJR.<br>* Other names: no other names;Drug: Paracetamol<br>* 1 g x 4/day<br>* Other names: no other names;Drug: Burana<br>* 400 mg x 3/day for three weeks<br>* Other names: NSAIDs are chosen in collaboration with the participant.;Drug: Pantoprazol<br>* 20mg x 1/day for three weeks<br>* Other names: no other names;Behavioral: Dietary counseling<br>* For participants with a BMI equal to or >25. The dietitian initiates a 3-month intervention that provides instruction and guidance in relation to diet and plans the number of visits according to the individual participant needs.<br>* Other names: no other names;Behavioral: Patient education<br>* The aim is to strengthen the participant's involvement in the treatment, so the participant will be in a position to handle, master and act reasonable in relation to their knee OA. This aspect of the intervention is based on principles from The Chronic Disease Self-Management Program, Lær at leve med kronisk sygdom (Learn to live with chronic illness) by The National Board of Health, Denmark and Artrosskolan Spenshult in Sweden.<br>* Other names: no other names;Procedure: TKR<br>* Surgical treatment with insertion of total knee replacement following standard procedures.<br>* Other names: Knee arthroplasty;Other: Insoles<br>* The position of the knee is assessed using Single Leg Mini Squat. On the basis of this test it is decided which of two types of insoles (Formthotics System) the participant should have (neutral with a lateral wedge or neutral). The participants will be advised to use the insoles in all shoes.<br>* Other names: no other names;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in KOOS4 From Baseline (Knee Injury and Osteoarthritis Outcome Score) | The average score for four of the five KOOS subscales, covering pain, symptoms, difficulties in functions of daily living, and quality of life (KOOS4), with scores ranging from 0 (worst) to 100 (best). Between group comparisons of treatment effect (change in KOOS4 from baseline to 1 year follow-up) will be dependent on data distribution. Between group comparisons of treatment effect (change in KOOS4 from baseline to 1 year follow-up) will be dependent on data distribution. We expect the change to be normally distributed and analysis will be made using a mixed model ANOVA with subject being a random factor and visit (baseline, 3, 6 and 12 months), treatment arm (TKA + MEDIC, MEDIC) and site (Frederikshavn, Farsoe) being fixed factors. Baseline KOOS4 will be a covariate. Furthermore interactions between the fixed factors will be included in the model. P-values and 95% CI will be presented to assess superiority. | Primary: 12months. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in EQ-5D From Baseline | Between groups comparisons of the change from baseline to the 1 year follow-up in all secondary endpoint will be handled similar to the primary endpoint. See Statistical analysis plan for further description (Links) Range of EQ-5D Descriptive Index is -0.59 to 1.00 (worst to best), while the EQ VAS goes from 0 to 100 (worst to best). | Primary: 12months. | 
| Change in Timed Up & Go (TUG) From Baseline |  | Primary: 12months. | 
| Change in 20-meter Walk From Baseline |  | Primary: 12months. | 
| Change in the Five Subscales of KOOS From Baseline | All subscales going from 0 to 100 (worst to best) | Primary: 12months. | 
| Weight Change in kg From Baseline | Weight change in kg measured without shoes at the same time of day and on the same scale | Primary: 12months. | 
| Proportion of Users of Pain Medication | With possible answers being yes and no | Baseline and 12months. | 
| Serious Adverse Events Related to the Index Knee | Adverse events (AE) and seriously adverse events (SAE) will be registered in three ways and divided into index knee or sites other than index knee. The project physiotherapist will record any adverse events that the participant experiences or tells them about. For the participants allocated to, or crossing over to, TKA, a project worker will look through hospital records to register if any pre-defined perioperative and postoperative adverse events occurred. At all follow-ups, the assessor will use open-probe questioning to assess adverse events in all participants | Primary: 12months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Middle Aged, Osteoarthritis, Knee, Treatment Outcome, Time Factors, Arthroplasty, Replacement, Rehabilitation, Combined Modality Therapy, Aged, Aged, 80 and over, Male, Female, Humans, Analysis of Variance