Structured Non-operative Treatment of Knee Osteoarthritis

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to test whether an algorithm for systematic non-surgical treatment consisting of corrective insoles, neuromuscular training, weight loss, patient education and pharmacological treatment with paracetamol, non steroidal anti inflammatory drugs (NSAIDs) and Pantoprazole provides further improvement in pain, function and quality of life than standard non-surgical treatment (information on the disease and how to treat it) in patients with knee osteoarthritis. The H1-hypothesis is that the treatment algorithm results in a greater increase in quality of life and functional capacity and greater reduction in pain than standard treatment 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
-----------------
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 osteoarthritis 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. However if the patient is not a candidate for total knee replacement, the patient most often receives only information on knee osteoarthritis, and on what they can do to treat the disorder and prevent it from being worse. This postponement of treatment can lead to a worsening of pain and function and a worse outcome after treatment. Therefore, the current treatment strategy for the patient group is problematic. The current practice may be due to the lack of studies with high level of evidence that have examined the optimal non-operative treatment approach and compared it with the current standard treatment for this group of patients.

Official Title
-----------------
Structured Non-operative Treatment of Knee Osteoarthritis - a Randomized Controlled Trial of Pain, Physical Function and Quality of Life With 12months Follow-up

Conditions
-----------------
Osteoarthritis of the Knee

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


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Knee-OA detected by x-ray (Kellgren & Lawrence grade 1 or greater) KOOS4 of ≤ 75 Considered not to be a candidate for Total Knee Replacement (TKR) by the orthopedic surgeon. The participant is > 18 years of age. The participant can provide relevant and adequate, informed consent. Exclusion Criteria: Prior TKA ipsilateral Rheumatoid arthritis Mean VAS > 60mm the last week on a 0-100mm scale Possible pregnancy or planning pregnancy; Inability to comply with the protocol; Inadequacy in written and spoken Danish.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

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;Drug: Paracetamol<br>* 1 g x 4/day<br>* Other names: No other;Drug: Burana<br>* 400 mg x 3/day for three weeks<br>* Other names: No other;Drug: Pantoprazole<br>* 20mg x 1/day for three weeks<br>* Other names: No other;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;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;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;|
| Active Comparator: Standard treatment<br>Information on knee osteoarthritis, and on what they can do to treat the disorder and prevent it from being worse. | Behavioral: Information<br>* Information on knee osteoarthritis, and on what they can do to treat the disorder and prevent it from being worse. Information will be given in a leaflet.<br>* Other names: No other;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in KOOS4 (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. 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 From Baseline in EQ-5D | 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 (available under 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 From Baseline in 20-meter Walk |  | Primary: 12months. | 
| Change in the Five KOOS Subscale Scores From Baseline | Range of all subscales are 0 to 100 (worst to best). | Primary: 12 months. | 
| 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. | 
| Number of Serious Adverse Events Reported at 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. | 
| Change From Baseline in Time From the Timed Up and Go |  | Primary: 12 months. | 

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