Back to resultsStructured Treatment of Osteoarthritis of the Knee With or Without Total Knee Replacement (MEDIC)
Primary Purpose
Osteoarthritis of the Knee
Status
Completed
Phase
Not Applicable
Locations
Denmark
Study Type
Interventional
Intervention
Neuromuscular training (NEMEX-TJR)
Paracetamol
Burana
Pantoprazol
Dietary counseling
Patient education
TKR
Insoles
Sponsored by
About this trial
This is an interventional treatment trial for Osteoarthritis of the Knee focused on measuring 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
Eligibility Criteria
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.
Sites / Locations
- Department of Occupational and Physiotherapy, Aalborg University Hospital
- Farsoe Hospital
- Vendsyssel Hospital, Frederikshavn
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Active Comparator
Active Comparator
Active Comparator
Arm Label
MEDIC
MEDIC + TKR
Observational Cohort
Arm Description
Medicine, Exercise, Diet, Insole and Cognitive/patient education (MEDIC) for three months.
Medicine, Exercise, Diet, Insole and Cognitive/patient education (MEDIC) for three months after a total knee replacement.
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.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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).
Change in Timed Up & Go (TUG) From Baseline
Change in 20-meter Walk From Baseline
Change in the Five Subscales of KOOS From Baseline
All subscales going from 0 to 100 (worst to best)
Weight Change in kg From Baseline
Weight change in kg measured without shoes at the same time of day and on the same scale
Proportion of Users of Pain Medication
With possible answers being yes and no
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
Full Information
NCT ID
NCT01410409
First Posted
August 2, 2011
Last Updated
September 14, 2017
Sponsor
Northern Orthopaedic Division, Denmark
Collaborators
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
1. Study Identification
Unique Protocol Identification Number
NCT01410409
Brief Title
Structured Treatment of Osteoarthritis of the Knee With or Without Total Knee Replacement
Acronym
MEDIC
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
September 2017
Overall Recruitment Status
Completed
Study Start Date
September 2011 (undefined)
Primary Completion Date
March 2015 (Actual)
Study Completion Date
March 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Northern Orthopaedic Division, Denmark
Collaborators
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
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Osteoarthritis of the Knee
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
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
100 (Actual)
8. Arms, Groups, and Interventions
Arm Title
MEDIC
Arm Type
Active Comparator
Arm Description
Medicine, Exercise, Diet, Insole and Cognitive/patient education (MEDIC) for three months.
Arm Title
MEDIC + TKR
Arm Type
Active Comparator
Arm Description
Medicine, Exercise, Diet, Insole and Cognitive/patient education (MEDIC) for three months after a total knee replacement.
Arm Title
Observational Cohort
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Other
Intervention Name(s)
Neuromuscular training (NEMEX-TJR)
Other Intervention Name(s)
no other names
Intervention Description
60min. of neuromuscular training two times a week for 3 months (12 weeks) using the neuromuscular training program called NEMEX-TJR.
Intervention Type
Drug
Intervention Name(s)
Paracetamol
Other Intervention Name(s)
no other names
Intervention Description
1 g x 4/day
Intervention Type
Drug
Intervention Name(s)
Burana
Other Intervention Name(s)
NSAIDs are chosen in collaboration with the participant.
Intervention Description
400 mg x 3/day for three weeks
Intervention Type
Drug
Intervention Name(s)
Pantoprazol
Other Intervention Name(s)
no other names
Intervention Description
20mg x 1/day for three weeks
Intervention Type
Behavioral
Intervention Name(s)
Dietary counseling
Other Intervention Name(s)
no other names
Intervention Description
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.
Intervention Type
Behavioral
Intervention Name(s)
Patient education
Other Intervention Name(s)
no other names
Intervention Description
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.
Intervention Type
Procedure
Intervention Name(s)
TKR
Other Intervention Name(s)
Total Knee Replacement, Knee arthroplasty
Intervention Description
Surgical treatment with insertion of total knee replacement following standard procedures.
Intervention Type
Other
Intervention Name(s)
Insoles
Other Intervention Name(s)
no other names
Intervention Description
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.
Primary Outcome Measure Information:
Title
Change in KOOS4 From Baseline (Knee Injury and Osteoarthritis Outcome Score)
Description
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.
Secondary Outcome Measure Information:
Title
Change in EQ-5D From Baseline
Description
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.
Title
Change in Timed Up & Go (TUG) From Baseline
Time Frame
Primary: 12months.
Title
Change in 20-meter Walk From Baseline
Time Frame
Primary: 12months.
Title
Change in the Five Subscales of KOOS From Baseline
Description
All subscales going from 0 to 100 (worst to best)
Time Frame
Primary: 12months.
Title
Weight Change in kg From Baseline
Description
Weight change in kg measured without shoes at the same time of day and on the same scale
Time Frame
Primary: 12months.
Title
Proportion of Users of Pain Medication
Description
With possible answers being yes and no
Time Frame
Baseline and 12months.
Title
Serious Adverse Events Related to the Index Knee
Description
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
Other Pre-specified Outcome Measures:
Title
Exploratory Outcomes
Description
Pain intensities on a 100 mm VAS with terminal descriptors of 'no pain' and 'worst pain possible' in various situations.
Number of sites with pain in the previous 24 hours shaded on a region-divided body chart
Pain location and type assessed using the Knee Pain Map.
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)
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.
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.
10. Eligibility
Sex
All
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Søren T Skou, PhD-student
Organizational Affiliation
Orthopaedic Research Unit, Aalborg University Hospital, Denmark
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Ewa M Roos, PhD
Organizational Affiliation
Institute of Sports Science and Clinical Biomechanics, University of Southern Denmark, Denmark
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Lars Arendt-Nielsen, Dr.Sci.Med.
Organizational Affiliation
Center for Sensory-Motor Interaction (SMI), Department of Health Sciences and Technology, Aalborg University
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Mogens B Laursen, PhD
Organizational Affiliation
Orthopaedic Surgery Research Unit, Aalborg University Hospital, Denmark
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Sten Rasmussen, MD
Organizational Affiliation
Orthopaedic Surgery Research Unit, Aalborg University Hospital, Denmark
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Michael S Rathleff, PhD-student
Organizational Affiliation
Orthopaedic Surgery Research Unit, Aalborg University Hospital, Denmark
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Ole H Simonsen, Dr.Med.
Organizational Affiliation
Orthopaedic Surgery Research Unit, Aalborg University Hospital, Denmark
Official's Role
Study Chair
Facility Information:
Facility Name
Department of Occupational and Physiotherapy, Aalborg University Hospital
City
Aalborg
ZIP/Postal Code
9000
Country
Denmark
Facility Name
Farsoe Hospital
City
Farsø
ZIP/Postal Code
9640
Country
Denmark
Facility Name
Vendsyssel Hospital, Frederikshavn
City
Frederikshavn
ZIP/Postal Code
9900
Country
Denmark
12. IPD Sharing Statement
Citations:
PubMed Identifier
11156538
Citation
Peat G, McCarney R, Croft P. Knee pain and osteoarthritis in older adults: a review of community burden and current use of primary health care. Ann Rheum Dis. 2001 Feb;60(2):91-7. doi: 10.1136/ard.60.2.91.
Results Reference
background
PubMed Identifier
18279766
Citation
Zhang W, Moskowitz RW, Nuki G, Abramson S, Altman RD, Arden N, Bierma-Zeinstra S, Brandt KD, Croft P, Doherty M, Dougados M, Hochberg M, Hunter DJ, Kwoh K, Lohmander LS, Tugwell P. OARSI recommendations for the management of hip and knee osteoarthritis, Part II: OARSI evidence-based, expert consensus guidelines. Osteoarthritis Cartilage. 2008 Feb;16(2):137-62. doi: 10.1016/j.joca.2007.12.013.
Results Reference
background
PubMed Identifier
14644851
Citation
Jordan KM, Arden NK, Doherty M, Bannwarth B, Bijlsma JW, Dieppe P, Gunther K, Hauselmann H, Herrero-Beaumont G, Kaklamanis P, Lohmander S, Leeb B, Lequesne M, Mazieres B, Martin-Mola E, Pavelka K, Pendleton A, Punzi L, Serni U, Swoboda B, Verbruggen G, Zimmerman-Gorska I, Dougados M; Standing Committee for International Clinical Studies Including Therapeutic Trials ESCISIT. EULAR Recommendations 2003: an evidence based approach to the management of knee osteoarthritis: Report of a Task Force of the Standing Committee for International Clinical Studies Including Therapeutic Trials (ESCISIT). Ann Rheum Dis. 2003 Dec;62(12):1145-55. doi: 10.1136/ard.2003.011742.
Results Reference
background
Citation
National Board of Health, Denmark. Referenceprogram for knæartrose. Copenhagen: National Board of Health, Denmark; 2007. [22.02.2010] found at: http://www.sst.dk/publ/Publ2007/PLAN/SfR/Refprg_knaeartrose.pdf
Results Reference
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PubMed Identifier
17719803
Citation
Zhang W, Moskowitz RW, Nuki G, Abramson S, Altman RD, Arden N, Bierma-Zeinstra S, Brandt KD, Croft P, Doherty M, Dougados M, Hochberg M, Hunter DJ, Kwoh K, Lohmander LS, Tugwell P. OARSI recommendations for the management of hip and knee osteoarthritis, part I: critical appraisal of existing treatment guidelines and systematic review of current research evidence. Osteoarthritis Cartilage. 2007 Sep;15(9):981-1000. doi: 10.1016/j.joca.2007.06.014. Epub 2007 Aug 27.
Results Reference
background
PubMed Identifier
11030685
Citation
Walker-Bone K, Javaid K, Arden N, Cooper C. Regular review: medical management of osteoarthritis. BMJ. 2000 Oct 14;321(7266):936-40. doi: 10.1136/bmj.321.7266.936. No abstract available.
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background
PubMed Identifier
16543327
Citation
Hunter DJ, Felson DT. Osteoarthritis. BMJ. 2006 Mar 18;332(7542):639-42. doi: 10.1136/bmj.332.7542.639. No abstract available.
Results Reference
background
PubMed Identifier
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Citation
Skou ST, Roos EM, Laursen MB, Rathleff MS, Arendt-Nielsen L, Simonsen O, Rasmussen S. A Randomized, Controlled Trial of Total Knee Replacement. N Engl J Med. 2015 Oct 22;373(17):1597-606. doi: 10.1056/NEJMoa1505467.
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PubMed Identifier
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Citation
Skou ST, Roos E, Laursen M, Arendt-Nielsen L, Rasmussen S, Simonsen O, Ibsen R, Larsen AT, Kjellberg J. Cost-effectiveness of total knee replacement in addition to non-surgical treatment: a 2-year outcome from a randomised trial in secondary care in Denmark. BMJ Open. 2020 Jan 15;10(1):e033495. doi: 10.1136/bmjopen-2019-033495.
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PubMed Identifier
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Citation
Skou ST, Roos EM, Laursen MB, Rathleff MS, Arendt-Nielsen L, Rasmussen S, Simonsen O. Total knee replacement and non-surgical treatment of knee osteoarthritis: 2-year outcome from two parallel randomized controlled trials. Osteoarthritis Cartilage. 2018 Sep;26(9):1170-1180. doi: 10.1016/j.joca.2018.04.014. Epub 2018 May 1.
Results Reference
derived
PubMed Identifier
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Citation
Arendt-Nielsen L, Simonsen O, Laursen MB, Roos EM, Rathleff MS, Rasmussen S, Skou ST. Pain and sensitization after total knee replacement or nonsurgical treatment in patients with knee osteoarthritis: Identifying potential predictors of outcome at 12 months. Eur J Pain. 2018 Jul;22(6):1088-1102. doi: 10.1002/ejp.1193. Epub 2018 Feb 15.
Results Reference
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PubMed Identifier
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Citation
Skou ST, Roos EM, Simonsen O, Laursen MB, Rathleff MS, Arendt-Nielsen L, Rasmussen S. The effects of total knee replacement and non-surgical treatment on pain sensitization and clinical pain. Eur J Pain. 2016 Nov;20(10):1612-1621. doi: 10.1002/ejp.878. Epub 2016 Mar 31.
Results Reference
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Citation
Skou ST, Rasmussen S, Simonsen O, Roos EM. Knee Confidence as It Relates to Self-reported and Objective Correlates of Knee Osteoarthritis: A Cross-sectional Study of 220 Patients. J Orthop Sports Phys Ther. 2015 Oct;45(10):765-71. doi: 10.2519/jospt.2015.5864. Epub 2015 Aug 24.
Results Reference
derived
PubMed Identifier
22571284
Citation
Skou ST, Roos EM, Laursen MB, Rathleff MS, Arendt-Nielsen L, Simonsen OH, Rasmussen S. Total knee replacement plus physical and medical therapy or treatment with physical and medical therapy alone: a randomised controlled trial in patients with knee osteoarthritis (the MEDIC-study). BMC Musculoskelet Disord. 2012 May 9;13:67. doi: 10.1186/1471-2474-13-67.
Results Reference
derived
Links:
URL
http://vbn.aau.dk/da/publications/statistical-analysis-plan-sap-for-medic(120b4fb2-c21a-47f4-9255-ec9851a59f55).html
Description
Link to the published statistical analysis plan
Learn more about this trial
Structured Treatment of Osteoarthritis of the Knee With or Without Total Knee Replacement
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