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

Not Applicable

Completed

Conditions: Osteoarthritis of the Knee

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

Registration Number: NCT01410409

Lead Sponsor: Northern Orthopaedic Division, Denmark

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 100

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
MEDIC + TKR	Paracetamol	Medicine, Exercise, Diet, Insole and Cognitive/patient education (MEDIC) for three months after a total knee replacement.
MEDIC	Burana	Medicine, Exercise, Diet, Insole and Cognitive/patient education (MEDIC) for three months.
MEDIC + TKR	Patient education	Medicine, Exercise, Diet, Insole and Cognitive/patient education (MEDIC) for three months after a total knee replacement.
MEDIC	Paracetamol	Medicine, Exercise, Diet, Insole and Cognitive/patient education (MEDIC) for three months.
MEDIC	Neuromuscular training (NEMEX-TJR)	Medicine, Exercise, Diet, Insole and Cognitive/patient education (MEDIC) for three months.
MEDIC	Patient education	Medicine, Exercise, Diet, Insole and Cognitive/patient education (MEDIC) for three months.
MEDIC + TKR	Burana	Medicine, Exercise, Diet, Insole and Cognitive/patient education (MEDIC) for three months after a total knee replacement.
MEDIC + TKR	Insoles	Medicine, Exercise, Diet, Insole and Cognitive/patient education (MEDIC) for three months after a total knee replacement.
MEDIC	Dietary counseling	Medicine, Exercise, Diet, Insole and Cognitive/patient education (MEDIC) for three months.
Observational Cohort	Neuromuscular training (NEMEX-TJR)	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.
Observational Cohort	Burana	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.
Observational Cohort	Patient education	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.
MEDIC	Insoles	Medicine, Exercise, Diet, Insole and Cognitive/patient education (MEDIC) for three months.
MEDIC + TKR	TKR	Medicine, Exercise, Diet, Insole and Cognitive/patient education (MEDIC) for three months after a total knee replacement.
Observational Cohort	Dietary counseling	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.
Observational Cohort	Insoles	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.
MEDIC + TKR	Neuromuscular training (NEMEX-TJR)	Medicine, Exercise, Diet, Insole and Cognitive/patient education (MEDIC) for three months after a total knee replacement.
MEDIC + TKR	Dietary counseling	Medicine, Exercise, Diet, Insole and Cognitive/patient education (MEDIC) for three months after a total knee replacement.
Observational Cohort	Pantoprazol	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.
Observational Cohort	TKR	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.
MEDIC	Pantoprazol	Medicine, Exercise, Diet, Insole and Cognitive/patient education (MEDIC) for three months.
MEDIC + TKR	Pantoprazol	Medicine, Exercise, Diet, Insole and Cognitive/patient education (MEDIC) for three months after a total knee replacement.
Observational Cohort	Paracetamol	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.

Primary Outcome Measures

Name	Time	Method
Change in KOOS4 From Baseline (Knee Injury and Osteoarthritis Outcome Score)	Primary: 12months.	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.

Secondary Outcome Measures

Name	Time	Method
Change in Timed Up & Go (TUG) From Baseline	Primary: 12months.
Change in the Five Subscales of KOOS From Baseline	Primary: 12months.	All subscales going from 0 to 100 (worst to best)
Change in 20-meter Walk From Baseline	Primary: 12months.
Weight Change in kg From Baseline	Primary: 12months.	Weight change in kg measured without shoes at the same time of day and on the same scale
Change in EQ-5D From Baseline	Primary: 12months.	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).
Proportion of Users of Pain Medication	Baseline and 12months.	With possible answers being yes and no
Serious Adverse Events Related to the Index Knee	Primary: 12months	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

Trial Locations

Locations (3): Department of Occupational and Physiotherapy, Aalborg University Hospital
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Aalborg, Denmark
Vendsyssel Hospital, Frederikshavn
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Frederikshavn, Denmark
Farsoe Hospital
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Farsø, Denmark