Osteoarthritis of the Knee
Conditions
Keywords
Osteoarthritis, Knee, Treatment Outcome, Time Factors, Arthroplasty, Replacement, Rehabilitation, Combined Modality Therapy, Middle Aged, Aged, Aged, 80 and over, Male, Female, Humans, Analysis of Variance
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.
Interventions
DRUGParacetamol
1 g x 4/day
DRUGBurana
400 mg x 3/day for three weeks
DRUGPantoprazol
20mg x 1/day for three weeks
60min. of neuromuscular training two times a week for 3 months (12 weeks) using the neuromuscular training program called NEMEX-TJR.
BEHAVIORALDietary counseling
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.
BEHAVIORALPatient education
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.
PROCEDURETKR
Surgical treatment with insertion of total knee replacement following standard procedures.
OTHERInsoles
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.
Sponsors
The Danish Rheumatism Association
Obel Family Foundation
Spar Nord Foundation
The Bevica Foundation
Aalborg University
Association of Danish Physiotherapists
Formthotics
Medical Specialist Heinrich Kopp's Grant
Danish Medical Association
Northern Orthopaedic Division, Denmark
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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). |
| Change in Timed Up & Go (TUG) From Baseline | Primary: 12months. | — |
| Proportion of Users of Pain Medication | Baseline and 12months. | With possible answers being yes and no |
| Change in the Five Subscales of KOOS From Baseline | Primary: 12months. | All subscales going from 0 to 100 (worst to best) |
| 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 |
| 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 |
| Change in 20-meter Walk From Baseline | Primary: 12months. | — |
Other
| Measure | Time frame | Description |
|---|---|---|
| Exploratory Outcomes | Baseline, 3months, 6months, 12months and 24 months. | 1. Pain intensities on a 100 mm VAS with terminal descriptors of 'no pain' and 'worst pain possible' in various situations. 2. Number of sites with pain in the previous 24 hours shaded on a region-divided body chart 3. Pain location and type assessed using the Knee Pain Map. 4. Maximum isometric muscle strength (converted to Nm using the length of the lower leg) measured bilaterally in knee flexion and knee extension in a make test using a handheld dynamometer (Powertrack II TM Commander from JTech Medical Industries, Salt Lake City, Utah, USA) 5. Pressure pain thresholds measured bilaterally using a handheld algometer (Algometer Type II, Somedic AB, Hoerby, Sweden)) at five sites at the knee and the m. tibialis anterior muscle. 6. Self-efficacy in improving pain, function and QOL in various situations using a 100 mm VAS with terminal descriptors of 'very unsure' and 'very sure'. Further exploratory objectives may be added later on. |
Countries
Denmark
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| MEDIC 60min. of neuromuscular training two times a week for 3 months (12 weeks) using the neuromuscular training program called NEMEX-TJR.
Paracetamol: 1 g x 4/day
Burana: 400 mg x 3/day
Pantoprazol: 20mg x 1/day
Dietary counseling: 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.
Patient education: 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.
Insoles: 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). | 50 |
| MEDIC + TKR TKR: Surgical treatment with insertion of total knee replacement following standard procedures.
Followed by:
60min. of neuromuscular training two times a week for 3 months (12 weeks) using the neuromuscular training program called NEMEX-TJR.
Paracetamol: 1 g x 4/day
Burana: 400 mg x 3/day
Pantoprazol: 20mg x 1/day
Dietary counseling: 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.
Patient education: 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.
Insoles: 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). | 50 |
| Total | 100 |
Baseline characteristics
| Characteristic | MEDIC | MEDIC + TKR | Total |
|---|---|---|---|
| Age, Continuous | 67.0 years STANDARD_DEVIATION 8.7 | 65.8 years STANDARD_DEVIATION 8.7 | 66.4 years STANDARD_DEVIATION 8.7 |
| Body Mass Index | 32.0 kg/m^2 STANDARD_DEVIATION 5.8 | 32.3 kg/m^2 STANDARD_DEVIATION 6.2 | 32.0 kg/m^2 STANDARD_DEVIATION 6 |
| Sex: Female, Male Female | 30 Participants | 32 Participants | 62 Participants |
| Sex: Female, Male Male | 20 Participants | 18 Participants | 38 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 38 / 50 | 45 / 50 |
| serious Total, serious adverse events | 5 / 50 | 20 / 50 |
Outcome results
Primary
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.
Time frame: Primary: 12months.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| MEDIC | Change in KOOS4 From Baseline (Knee Injury and Osteoarthritis Outcome Score) | 16.0 units on a scale |
| MEDIC + TKR | Change in KOOS4 From Baseline (Knee Injury and Osteoarthritis Outcome Score) | 32.5 units on a scale |
Secondary
Change in 20-meter Walk From Baseline
Time frame: Primary: 12months.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| MEDIC | Change in 20-meter Walk From Baseline | -1.0 sec |
| MEDIC + TKR | Change in 20-meter Walk From Baseline | -2.9 sec |
Secondary
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).
Time frame: Primary: 12months.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| MEDIC | Change in EQ-5D From Baseline | Descriptive index | 0.115 units on a scale |
| MEDIC | Change in EQ-5D From Baseline | Visual-analogue scale | 10.2 units on a scale |
| MEDIC + TKR | Change in EQ-5D From Baseline | Descriptive index | 0.206 units on a scale |
| MEDIC + TKR | Change in EQ-5D From Baseline | Visual-analogue scale | 15.0 units on a scale |
Secondary
Change in the Five Subscales of KOOS From Baseline
All subscales going from 0 to 100 (worst to best)
Time frame: Primary: 12months.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| MEDIC | Change in the Five Subscales of KOOS From Baseline | Symptoms | 11.4 units on a scale |
| MEDIC | Change in the Five Subscales of KOOS From Baseline | Quality of Life | 17.8 units on a scale |
| MEDIC | Change in the Five Subscales of KOOS From Baseline | Activities of Daily Living | 17.6 units on a scale |
| MEDIC | Change in the Five Subscales of KOOS From Baseline | Sports and recreation | 19.3 units on a scale |
| MEDIC | Change in the Five Subscales of KOOS From Baseline | Pain | 17.2 units on a scale |
| MEDIC + TKR | Change in the Five Subscales of KOOS From Baseline | Sports and recreation | 34.5 units on a scale |
| MEDIC + TKR | Change in the Five Subscales of KOOS From Baseline | Pain | 34.8 units on a scale |
| MEDIC + TKR | Change in the Five Subscales of KOOS From Baseline | Symptoms | 26.4 units on a scale |
| MEDIC + TKR | Change in the Five Subscales of KOOS From Baseline | Activities of Daily Living | 30.0 units on a scale |
| MEDIC + TKR | Change in the Five Subscales of KOOS From Baseline | Quality of Life | 38.2 units on a scale |
Secondary
Change in Timed Up & Go (TUG) From Baseline
Time frame: Primary: 12months.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| MEDIC | Change in Timed Up & Go (TUG) From Baseline | -1.2 sec |
| MEDIC + TKR | Change in Timed Up & Go (TUG) From Baseline | -2.4 sec |
Secondary
Proportion of Users of Pain Medication
With possible answers being yes and no
Time frame: Baseline and 12months.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MEDIC | Proportion of Users of Pain Medication | Baseline | 0.58 proportion of participants |
| MEDIC | Proportion of Users of Pain Medication | 12months | 0.41 proportion of participants |
| MEDIC + TKR | Proportion of Users of Pain Medication | Baseline | 0.67 proportion of participants |
| MEDIC + TKR | Proportion of Users of Pain Medication | 12months | 0.26 proportion of participants |
Secondary
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
Time frame: Primary: 12months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MEDIC | Serious Adverse Events Related to the Index Knee | 1 Serious adverse events related to knee |
| MEDIC + TKR | Serious Adverse Events Related to the Index Knee | 8 Serious adverse events related to knee |
Secondary
Weight Change in kg From Baseline
Weight change in kg measured without shoes at the same time of day and on the same scale
Time frame: Primary: 12months.
Population: Only patients with a BMI equal to or \>25 were included in the analysis
| Arm | Measure | Value (MEAN) |
|---|---|---|
| MEDIC | Weight Change in kg From Baseline | -2.6 kg |
| MEDIC + TKR | Weight Change in kg From Baseline | 0.1 kg |
Other Pre-specified
Exploratory Outcomes
1. Pain intensities on a 100 mm VAS with terminal descriptors of 'no pain' and 'worst pain possible' in various situations. 2. Number of sites with pain in the previous 24 hours shaded on a region-divided body chart 3. Pain location and type assessed using the Knee Pain Map. 4. Maximum isometric muscle strength (converted to Nm using the length of the lower leg) measured bilaterally in knee flexion and knee extension in a make test using a handheld dynamometer (Powertrack II TM Commander from JTech Medical Industries, Salt Lake City, Utah, USA) 5. Pressure pain thresholds measured bilaterally using a handheld algometer (Algometer Type II, Somedic AB, Hoerby, Sweden)) at five sites at the knee and the m. tibialis anterior muscle. 6. Self-efficacy in improving pain, function and QOL in various situations using a 100 mm VAS with terminal descriptors of 'very unsure' and 'very sure'. Further exploratory objectives may be added later on.
Time frame: Baseline, 3months, 6months, 12months and 24 months.
Population: Will be reported in later publications, as it is exploratory outcomes