Trial Outcomes & Findings for Structured Non-operative Treatment of Knee Osteoarthritis (NCT NCT01535001)

Last Updated: 2017-10-16

Results Overview

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.

Recruitment status

COMPLETED

Study phase

Target enrollment

100 participants

Primary outcome timeframe

Primary: 12months.

Results posted on

2017-10-16

Participant Flow

Participant milestones

Participant milestones
Measure	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 Pantoprazole: 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). The participants will be advised to use the insoles in all shoes.	Standard Treatment Information on knee osteoarthritis, and on what they can do to treat the disorder and prevent it from being worse. Information: 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.
Overall Study STARTED	50	50
Overall Study COMPLETED	47	44
Overall Study NOT COMPLETED	3	6

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Structured Non-operative Treatment of Knee Osteoarthritis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	MEDIC n=50 Participants 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 Pantoprazole: 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). The participants will be advised to use the insoles in all shoes.	Standard Treatment n=50 Participants Information on knee osteoarthritis, and on what they can do to treat the disorder and prevent it from being worse. Information: 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.	Total n=100 Participants Total of all reporting groups
Age, Continuous	64.8 years STANDARD_DEVIATION 8.7 • n=5 Participants	67.1 years STANDARD_DEVIATION 9.1 • n=7 Participants	66.0 years STANDARD_DEVIATION 8.9 • n=5 Participants
Sex: Female, Male Female	26 Participants n=5 Participants	25 Participants n=7 Participants	51 Participants n=5 Participants
Sex: Female, Male Male	24 Participants n=5 Participants	25 Participants n=7 Participants	49 Participants n=5 Participants
Body Mass Index	30.6 kg/m^2 STANDARD_DEVIATION 5.6 • n=5 Participants	29.4 kg/m^2 STANDARD_DEVIATION 5.2 • n=7 Participants	30.0 kg/m^2 STANDARD_DEVIATION 5.4 • n=5 Participants

PRIMARY outcome

Timeframe: Primary: 12months.

Outcome measures

Outcome measures
Measure	MEDIC n=50 Participants 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 Pantoprazole: 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). The participants will be advised to use the insoles in all shoes.	Standard Treatment n=50 Participants Information on knee osteoarthritis, and on what they can do to treat the disorder and prevent it from being worse. Information: 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.
Change From Baseline in KOOS4 (Knee Injury and Osteoarthritis Outcome Score)	18.2 units on a scale Interval 13.0 to 23.4	7.1 units on a scale Interval 1.4 to 12.9

SECONDARY outcome

Timeframe: 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 (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).

Outcome measures

Outcome measures
Measure	MEDIC n=50 Participants 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 Pantoprazole: 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). The participants will be advised to use the insoles in all shoes.	Standard Treatment n=50 Participants Information on knee osteoarthritis, and on what they can do to treat the disorder and prevent it from being worse. Information: 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.
Change From Baseline in EQ-5D Descriptive index	0.140 units on a scale Interval 0.095 to 0.186	0.075 units on a scale Interval 0.018 to 0.132
Change From Baseline in EQ-5D EQ VAS	5.3 units on a scale Interval -0.4 to 11.0	7.2 units on a scale Interval 0.1 to 14.2

SECONDARY outcome

Timeframe: Primary: 12months.

Outcome measures

Outcome measures
Measure	MEDIC n=50 Participants 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 Pantoprazole: 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). The participants will be advised to use the insoles in all shoes.	Standard Treatment n=50 Participants Information on knee osteoarthritis, and on what they can do to treat the disorder and prevent it from being worse. Information: 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.
Change From Baseline in 20-meter Walk	-1.2 sec Interval -1.6 to -0.8	-0.6 sec Interval -1.1 to -0.1

SECONDARY outcome

Timeframe: Primary: 12 months.

Range of all subscales are 0 to 100 (worst to best).

Outcome measures

Outcome measures
Measure	MEDIC n=50 Participants 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 Pantoprazole: 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). The participants will be advised to use the insoles in all shoes.	Standard Treatment n=50 Participants Information on knee osteoarthritis, and on what they can do to treat the disorder and prevent it from being worse. Information: 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.
Change in the Five KOOS Subscale Scores From Baseline Pain	18.7 units on a scale Interval 12.9 to 24.6	9.3 units on a scale Interval 2.9 to 15.6
Change in the Five KOOS Subscale Scores From Baseline Symptoms	16.3 units on a scale Interval 10.6 to 22.0	7.7 units on a scale Interval 1.5 to 13.9
Change in the Five KOOS Subscale Scores From Baseline Activities of Daily Living	18.7 units on a scale Interval 12.6 to 24.8	5.9 units on a scale Interval -0.8 to 12.6
Change in the Five KOOS Subscale Scores From Baseline Sports and recreation	16.0 units on a scale Interval 7.8 to 24.1	12.0 units on a scale Interval 4.8 to 19.3
Change in the Five KOOS Subscale Scores From Baseline Quality of Life	19.0 units on a scale Interval 12.9 to 25.2	5.5 units on a scale Interval -1.1 to 12.1

SECONDARY outcome

Timeframe: Primary: 12months.

Population: Only patients with a BMI equal to or \>25 were included in this analysis.

Weight change in kg measured without shoes at the same time of day and on the same scale

Outcome measures

Outcome measures
Measure	MEDIC n=42 Participants 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 Pantoprazole: 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). The participants will be advised to use the insoles in all shoes.	Standard Treatment n=37 Participants Information on knee osteoarthritis, and on what they can do to treat the disorder and prevent it from being worse. Information: 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.
Weight Change in kg From Baseline	-2.4 kg Interval -3.8 to -1.1	-2.4 kg Interval -4.1 to -0.6

SECONDARY outcome

Timeframe: Baseline and 12months.

With possible answers being yes and no

Outcome measures

Outcome measures
Measure	MEDIC n=50 Participants 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 Pantoprazole: 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). The participants will be advised to use the insoles in all shoes.	Standard Treatment n=50 Participants Information on knee osteoarthritis, and on what they can do to treat the disorder and prevent it from being worse. Information: 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.
Proportion of Users of Pain Medication Baseline	0.64 proportion of participants Interval 0.5 to 0.76	0.56 proportion of participants Interval 0.42 to 0.69
Proportion of Users of Pain Medication 12months	0.39 proportion of participants Interval 0.26 to 0.54	0.57 proportion of participants Interval 0.42 to 0.71

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	MEDIC n=50 Participants 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 Pantoprazole: 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). The participants will be advised to use the insoles in all shoes.	Standard Treatment n=50 Participants Information on knee osteoarthritis, and on what they can do to treat the disorder and prevent it from being worse. Information: 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.
Number of Serious Adverse Events Reported at Index Knee	13 Serious adverse events related to knee	24 Serious adverse events related to knee

SECONDARY outcome

Timeframe: Primary: 12 months.

Outcome measures

Outcome measures
Measure	MEDIC n=50 Participants 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 Pantoprazole: 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). The participants will be advised to use the insoles in all shoes.	Standard Treatment n=50 Participants Information on knee osteoarthritis, and on what they can do to treat the disorder and prevent it from being worse. Information: 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.
Change From Baseline in Time From the Timed Up and Go	-1.4 sec Interval -1.9 to -0.9	-1.1 sec Interval -1.7 to -0.5

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, 3months, 6months, 12months and 24months

Population: Since this is exploratory outcomes they will be analyzed in future publications.

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 measured bilaterally in knee flexion and knee extension in a make test using a handheld dynamometer (Powertrack II TM Commander). 5. Pressure pain thresholds measured bilaterally using a handheld algometer (Algometer Type II) at five sites at the knee and the m. tibialis anterior muscle and the m. extensor carpi radialis longus. 6. Postural balance assessed using an instrumented force platform (Good Balance), measuring the centre of pressure excursion. 7. 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'.

Outcome measures

Outcome data not reported

Adverse Events

MEDIC

Serious events: 11 serious events

Other events: 17 other events

Deaths: 0 deaths

Standard Treatment

Serious events: 14 serious events

Other events: 14 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	MEDIC n=50 participants at risk 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 Pantoprazole: 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). The participants will be advised to use the insoles in all shoes.	Standard Treatment n=50 participants at risk Information on knee osteoarthritis, and on what they can do to treat the disorder and prevent it from being worse. Information: 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.
Musculoskeletal and connective tissue disorders Total knee replacement	6.0% 3/50 • Number of events 3	10.0% 5/50 • Number of events 5
Musculoskeletal and connective tissue disorders Arthrodesis of contralateral foot	2.0% 1/50 • Number of events 1	0.00% 0/50
Skin and subcutaneous tissue disorders Erysipelas	2.0% 1/50 • Number of events 1	0.00% 0/50
Gastrointestinal disorders Intestinal cancer	2.0% 1/50 • Number of events 1	0.00% 0/50
Respiratory, thoracic and mediastinal disorders Pneumonia	2.0% 1/50 • Number of events 1	0.00% 0/50
Musculoskeletal and connective tissue disorders Knee arthroscopy	6.0% 3/50 • Number of events 3	2.0% 1/50 • Number of events 1
Blood and lymphatic system disorders Blood transfusion during TKR surgery	0.00% 0/50	2.0% 1/50 • Number of events 1
Musculoskeletal and connective tissue disorders pain without loosening of the prosthesis	2.0% 1/50 • Number of events 1	6.0% 3/50 • Number of events 3
Musculoskeletal and connective tissue disorders Fracture of os sacrum	0.00% 0/50	2.0% 1/50 • Number of events 1
Musculoskeletal and connective tissue disorders Gout	0.00% 0/50	4.0% 2/50 • Number of events 2
Musculoskeletal and connective tissue disorders Low back pain radiating to leg	0.00% 0/50	2.0% 1/50 • Number of events 1
Musculoskeletal and connective tissue disorders Frature of collum femoris	0.00% 0/50	2.0% 1/50 • Number of events 1
Nervous system disorders Guillain-Barre syndrome	2.0% 1/50 • Number of events 1	0.00% 0/50
General disorders Death	2.0% 1/50 • Number of events 1	2.0% 1/50 • Number of events 1
Neoplasms benign, malignant and unspecified (incl cysts and polyps) ovarian cyst	0.00% 0/50	2.0% 1/50 • Number of events 1
Vascular disorders heart problems	0.00% 0/50	2.0% 1/50 • Number of events 1
Respiratory, thoracic and mediastinal disorders severe physical decline due to influenza	0.00% 0/50	2.0% 1/50 • Number of events 1
Vascular disorders renal-artery stenosis	0.00% 0/50	2.0% 1/50 • Number of events 1
Vascular disorders Atherosclerosis demanding angioplasty	0.00% 0/50	2.0% 1/50 • Number of events 1
Ear and labyrinth disorders canalolithiasis	0.00% 0/50	2.0% 1/50 • Number of events 1
Musculoskeletal and connective tissue disorders Instability after TKR	0.00% 0/50	2.0% 1/50 • Number of events 1
Musculoskeletal and connective tissue disorders Swelling after TKR	0.00% 0/50	2.0% 1/50 • Number of events 1

Other adverse events

Other adverse events
Measure	MEDIC n=50 participants at risk 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 Pantoprazole: 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). The participants will be advised to use the insoles in all shoes.	Standard Treatment n=50 participants at risk Information on knee osteoarthritis, and on what they can do to treat the disorder and prevent it from being worse. Information: 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.
Musculoskeletal and connective tissue disorders Pain in index knee	28.0% 14/50 • Number of events 14	24.0% 12/50 • Number of events 12
Musculoskeletal and connective tissue disorders Swelling in index knee	6.0% 3/50 • Number of events 3	2.0% 1/50 • Number of events 1
Musculoskeletal and connective tissue disorders Decreased range of motion in index knee	2.0% 1/50 • Number of events 1	0.00% 0/50
Musculoskeletal and connective tissue disorders Calor around index knee	2.0% 1/50 • Number of events 1	2.0% 1/50 • Number of events 1
Musculoskeletal and connective tissue disorders Rubor	0.00% 0/50	2.0% 1/50 • Number of events 1
Musculoskeletal and connective tissue disorders Achilles Tendinopathy	4.0% 2/50 • Number of events 2	0.00% 0/50
Musculoskeletal and connective tissue disorders Broken toe	2.0% 1/50 • Number of events 1	0.00% 0/50
Musculoskeletal and connective tissue disorders foot painof short duration	2.0% 1/50 • Number of events 1	0.00% 0/50
Musculoskeletal and connective tissue disorders intermittent hip pain	2.0% 1/50 • Number of events 1	2.0% 1/50 • Number of events 1
Musculoskeletal and connective tissue disorders sciatic nerve pain of short duration	2.0% 1/50 • Number of events 1	0.00% 0/50
Musculoskeletal and connective tissue disorders ankle sprain (grade I)	0.00% 0/50	2.0% 1/50 • Number of events 1
Musculoskeletal and connective tissue disorders pain in the contralateral knee	0.00% 0/50	2.0% 1/50 • Number of events 1
Musculoskeletal and connective tissue disorders hamstring strain	0.00% 0/50	2.0% 1/50 • Number of events 1

Additional Information

Dr. Søren T. Skou

Aalborg University Hospital

Phone: +4523708640

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place