Knee Osteoarthritis
Conditions
Brief summary
The main purpose of this study is to compare the cartilage volume loss at the Baseline visit and after 24 months of treatment in patients treated with CHONDROITIN SULPHATE (CONDROSAN) 1200 mg daily vs. patients treated with CELECOXIB 200 mg daily.
Detailed description
To compare long term disease modifiying and symptomatic effects at the Baseline visit and after 24 months of treatment in patients treated with CHONDROITIN SULPHATE 1200 mg daily vs. patients treated with CELECOXIB 200 mg daily.
Interventions
Chondroitin sulphate 1200 mg/day, 24 months treatment period
DRUGCelecoxib
Celecoxib 200 mg/day, 24 months treatment period
Sponsors
Bioiberica
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Individuals of either sex, aged 40 years and more * Subjects presenting primary OA of the knee according to ACR criteria with signs of synovitis (warmth, swelling or effusion * OA of radiological stages 2 and 3 according to Kellgren-Lawrence; * Minimum joint space width ≥2 mm in the medial femorotibial compartment on standing knee X-ray * VAS of pain while walking ≥ 40 mm
Exclusion criteria
* Known allergy to CHONDROITIN SULPHATE, hypersensitivity to CELECOXIB, demonstrated allergic-type reactions to sulphonamides, experienced asthma, urticaria or allergic-type reactions after taking sulphonamides, aspirin (acetyl salicylic acid \[ASA\]), lactose or NSAIDs * Active malignancy of any type or history of a malignancy within the last five years other than basal cell carcinoma * Increased risk for prostate cancer, with prostate cancer, or with a history of prostate cancer within the last five years * Subjects with other bone and articular diseases (antecedents and/or current signs) such as chondrocalcinosis, Paget's disease of the ipsilateral limb to the target knee, rheumatoid arthritis, aseptic osteonecrosis, gout, septic arthritis, ochronosis, acromegaly, haemochromatosis, Wilson's disease, osteochondromatosis seronegative spondylo-arthropathy, mixed connective tissue disease, collagen vascular disease, psoriasis, inflammatory bowel disease * Isolated knee lateral compartment OA defined by joint space loss in the lateral compartment only * Class IV functional capacity using the American Rheumatism Association criteria * Have had surgery in any lower limb or arthroscopy, aspiration or lavage in any lower limb joint within 180 days of the Baseline Visit * History of heart attack or stroke, or experienced serious chest pain related to heart disease, or who have had serious diseases of the heart such as congestive heart failure * High risk of CV events, according to the AHA assessment of CV risk tables * History of recurrent UGI ulceration or active inflammatory bowel disease (e.g., Crohn's disease or ulcerative colitis), a significant coagulation defect, or any other condition, which in the investigator's opinion might preclude the chronic use of CELECOXIB. Subjects may, at the Investigator's discretion, take a PPI or antacids daily as required * Have been diagnosed as having or have been treated for oesophageal, gastric, pyloric channel, or duodenal ulceration within 30 days prior to receiving the first dose of study medication * Subjects using corticosteroids (oral, injectable; exception of intraarticular/soft tissue injection at the exclusion of the target knee), indomethacin, tramadol, codeine, empracet, therapeutic dose of glucosamine or CHONDROITIN SULPHATE during the 12 weeks preceding inclusion * Using hyaluronic acid (intra-articular target knee) during the 26 weeks preceding inclusion * Using Natural Health Products (e.g. capsaicin, boswellia, willow bark), and creams and analgesic gels (e.g. camphor and alcohol based gels) during one week preceding baseline; * Using Natural Health Products susceptible to increase the risk of bleeding (e.g. garlic, dong quai, etc.) during one week preceding baseline; * Receiving radioactive synovectomy (target knee) during the 12 weeks preceding inclusion; * Subjects who are receiving NSAID and do not want to stop during the study * If treatment of osteoporosis (biphosphonates, SERMS, THS) is necessary, it will have to be continued, unmodified, for the entire duration of the study * Have used medications with MMP-inhibitory properties (e.g. tetracycline or structurally related compounds) within 28 days prior to the Baseline Visit * Are taking lithium carbonate, phenytoin or anticoagulants (with the exception of ASA up to a maximum daily dose of 325 mg) * Have received chondrocyte transplants in any lower extremity joint * Use oral or topical COXIBs, calcitonin or immunosuppressive drugs
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cartilage Volume Loss of the Lateral Compartment | 12 months (Day 364) and 24 months (Day 728) | To compare the cartilage volume loss of the lateral compartment (femoral condyle and tibial plateau) at the Baseline visit and after 12 and 24 months of treatment either with CHONDROITIN SULPHATE (CONDROSAN) 1200 mg daily or with CELECOXIB 200 mg daily. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cartilage Volume in the Medial Compartment | 12 months (Day 364) and 24 months (Day 728) | To compare the cartilage volume loss of the medial compartment at the Baseline visit and after 12 and 24 months. |
| Synovial Membrane Thickness | Baseline, 12 months (Day 364) and 24 months (Day 728) | To compare the severity of synovitis score (Thickness of the Synovial Membrane in mm) in Global Knee , at the baseline visit and the follow-up visits in subjects treated either with CHONDROITIN SULPHATE (CONDROSAN) or CELECOXIB. The severity of synovitis was evaluated through four regions of interest (ROIs) in the images of the axial T1-weighted acquisition complemented with the use of the images of the axial T2-weighted acquisition. The thickness of the synovial membrane was evaluated in the global knee and each of the ROIs and results were expressed in millimetres. The four ROIs were the proximal lateral, distal lateral, proximal medial and distal medial. |
| Bone Marrow Lesions Score | Baseline, 12 months (Day 364) and 24 months (Day 728) | To compare the bone marrow lesions (BMLs) score in the global knee and the different sub regions at the baseline visit and the follow-up visits in subjects treated either with CHONDROITIN SULPHATE (CONDROSAN) or CELECOXIB. The BMLs were assessed in the global knee and the different sub region of the knee (medial trochlea, plateau of the medial femoro-tibial joint, femur of the medial femoro-tibial joint, medial posterior condyle, lateral trochlea, plateau of the lateral femoro-tibial joint, femur of the lateral femoro-tibial joint, lateral posterior femur). The BMLs score was defined as a grade (between 0 and 3) in each knee sub region and summed to derive a global knee score ranging between 0 (absent) and 30 (present). Specifically, each grade was scored as follows: * Grade 0 = Absence of lesion in the sub region * Grade 1 = less than 25% of the surface * Grade 2 = 25-50% of the surface * Grade 3 = more than 50% of the surface |
| Synovial Fluid Volume | Baseline, 12 months (Day 364) and 24 months (Day 728) | To compare the synovial fluid volume of the global knee at the Baseline visit and after 24 months. |
| Percentage of Participants With the Presence of Extrusion in the Meniscus | Baseline, 12 months (Day 364) and 24 months (Day 728) | The presence of a meniscal extrusion was assessed in each of sub regions. The absence of a severe extrusion in all the sub regions was considered as an absence (score=0) of a severe extrusion in the meniscus. The presence of a severe extrusion in at least one region of the meniscus was sufficient to consider the presence (score=1) of a severe extrusion in the meniscus. |
| Visual Analog Scale (VAS) | Baseline, 12 months (Day 364) and 24 months (Day 728) | Visual Analogue Scale: 0 No Pain 10 Maximum Pain Huskisson's VAS measures global pain intensity. Patients were asked to quantify their disease status on a 10 cm VAS as follows: Please indicate the severity of knee pain experienced during the last 48 hours by marking a (I) through the line. Left hand marker represents No pain and right hand marker represents The worst pain imaginable. |
| Cartilage Volume Loss of the Global Knee | 12 months (Day 364) and 24 months (Day 728) | To compare the cartilage volume loss of the global knee at the Baseline visit and after 12 and 24 months. |
| WOMAC Stiffness Subscale | Baseline, 12 months (Day 364) and 24 months (Day 728) | Western Ontario & McMaster Universities Osteoarthritis Index, from 0 No Stiffness to 20 Maximum Stiffness WOMAC stiffness subscale was used to measure the stiffness of the knee with pain. Two items are used to assess stiffness grade: after first waking and later in the day.Each item is a 10 cm VAS with 0 and 10 cm representing no difficulty and extreme difficulty respectively. |
| WOMAC Function Subscale | Baseline, 12 months (Day 364) and 24 months (Day 728) | Western Ontario & McMaster Universities Osteoarthritis Index, from 0 No Function to 170 Maximum Function WOMAC functional limitation subscale was used to measure the functionality of the knee with pain. Seventeen items are used to assess functionality of the knee: tair use, rising from sitting, standing, bending, walking, getting in / out of a car, shopping, putting on / taking off socks, rising from bed, lying in bed, getting in / out of bath, sitting, getting on / off toilet, heavy household duties, light household duties. Each item is a 10 cm VAS with 0 and 10 cm representing no difficulty and extreme difficulty respectively. |
| Short Form (SF-36) Health Survey | Baseline, 12 months (Day 364) and 24 months (Day 728) | The SF-36 is composed of 35 items measuring: * 8 health concepts (or dimensions), \[(Physical Functioning (PF), Role Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role Emotional (RE) and Mental Health (MH)\] * and 1 reported health transition item. The 8 health concepts are summarized in 1 physical (PCS) and 1 mental (MCS) component summary measures. PCS is represented by physical function, role limitations-physical, pain, and general health perception. MCS is represented by vitality, social function, role limitations-emotional, and mental health. Subscale items are summed and scaled from 0-100 to give subscale scores; 0= worst health related quality of life (HRQL), 100=best HRQL. PCS and MCS summary scores are constructed as T-scores (mean =50, standard deviation=10) with no minimum or maximum score; higher scores indicate better health status. |
| Percentage of Participants With Presence of Joint Swelling and Effusion | Baseline, 12 months (Day 364) and 24 months (Day 728) | Study knees were evaluated at each visit for the presence or absence of swelling and effusion. |
| Use of Acetaminophen | 3 months (Day 91), 6 momnths (Day 182), 12 months (Day 364), 18 monts (Day 546) and 24 months (Day 728) | Consumption of Acetaminophen: At each post-baseline visit, the investigator had to assess the consumption of acetaminophen, rescue analgesic authorised throughout the study, by reporting the number of caplets dispensed/retrieved since the previous visit. Daily consumption of acetaminophen was calculated as an average. |
| WOMAC Pain Subscale | Baseline, 12 months (Day 364) and 24 months (Day 728) | Western Ontario & McMaster Universities Osteoarthritis Index (WOMAC) Pain subscale Score Range: 0 (no pain) - 50 (maximum pain) The study was designed such that the outcome of primary interest is knee pain related to OA. The measure selected to best evaluate this is an improvement in the WOMAC pain subscales. This subscale consists of 5 items which assesses the pain during walking, using stairs, in bed, sitting or lying, and standing.Each item is a 10 cm VAS with 0 and 10 cm representing no pain and extreme pain respectively. |
Countries
Canada
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Chondroitin Sulfate (Condrosan) CHONDROITIN SULPHATE Group: 1200 mg (three capsules of 400 mg each) taken once a day in the morning
Chondroitin sulfate: Chondroitin sulphate 1200 mg/day, 24 months treatment period | 97 |
| Celecoxib CELECOXIB Group: 200 mg (one capsule of 200 mg CELECOXIB + two placebo capsules) taken in the morning
Celecoxib: Celecoxib 200 mg/day, 24 months treatment period | 97 |
| Total | 194 |
Baseline characteristics
| Characteristic | Chondroitin Sulfate (Condrosan) | Celecoxib | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 38 Participants | 41 Participants | 79 Participants |
| Age, Categorical Between 18 and 65 years | 59 Participants | 56 Participants | 115 Participants |
| Age, Continuous | 61.4 years STANDARD_DEVIATION 9.3 | 61.3 years STANDARD_DEVIATION 8.5 | 61.3 years STANDARD_DEVIATION 8.9 |
| Cartilage Volume in the Global Knee | 12665 cubic milimeters STANDARD_DEVIATION 4259 | 12048 cubic milimeters STANDARD_DEVIATION 2969 | 12356 cubic milimeters STANDARD_DEVIATION 3674 |
| Cartilage Volume in the Lateral Compartment | 6606 cubic milimeters STANDARD_DEVIATION 2332 | 6343 cubic milimeters STANDARD_DEVIATION 1565 | 6475 cubic milimeters STANDARD_DEVIATION 1985 |
| Cartilage Volume in the Medial Compartment | 6059 cubic milimeters STANDARD_DEVIATION 2031 | 5705 cubic milimeters STANDARD_DEVIATION 1572 | 5882 cubic milimeters STANDARD_DEVIATION 1820 |
| Sex: Female, Male Female | 44 Participants | 36 Participants | 80 Participants |
| Sex: Female, Male Male | 53 Participants | 61 Participants | 114 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 78 / 97 | 79 / 97 |
| serious Total, serious adverse events | 10 / 97 | 6 / 97 |
Outcome results
Primary
Cartilage Volume Loss of the Lateral Compartment
To compare the cartilage volume loss of the lateral compartment (femoral condyle and tibial plateau) at the Baseline visit and after 12 and 24 months of treatment either with CHONDROITIN SULPHATE (CONDROSAN) 1200 mg daily or with CELECOXIB 200 mg daily.
Time frame: 12 months (Day 364) and 24 months (Day 728)
Population: Intention-To-Treat
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Chondroitin Sulfate (Condrosan) | Cartilage Volume Loss of the Lateral Compartment | Visit 6 (Day 364) | 6408 cubic milimeters | Standard Deviation 97 |
| Chondroitin Sulfate (Condrosan) | Cartilage Volume Loss of the Lateral Compartment | Visit 9 (Day 728) | 6196 cubic milimeters | Standard Deviation 99 |
| Celecoxib (Celebrex) | Cartilage Volume Loss of the Lateral Compartment | Visit 6 (Day 364) | 6196 cubic milimeters | Standard Deviation 97 |
| Celecoxib (Celebrex) | Cartilage Volume Loss of the Lateral Compartment | Visit 9 (Day 728) | 6143 cubic milimeters | Standard Deviation 99 |
Secondary
Bone Marrow Lesions Score
To compare the bone marrow lesions (BMLs) score in the global knee and the different sub regions at the baseline visit and the follow-up visits in subjects treated either with CHONDROITIN SULPHATE (CONDROSAN) or CELECOXIB. The BMLs were assessed in the global knee and the different sub region of the knee (medial trochlea, plateau of the medial femoro-tibial joint, femur of the medial femoro-tibial joint, medial posterior condyle, lateral trochlea, plateau of the lateral femoro-tibial joint, femur of the lateral femoro-tibial joint, lateral posterior femur). The BMLs score was defined as a grade (between 0 and 3) in each knee sub region and summed to derive a global knee score ranging between 0 (absent) and 30 (present). Specifically, each grade was scored as follows: * Grade 0 = Absence of lesion in the sub region * Grade 1 = less than 25% of the surface * Grade 2 = 25-50% of the surface * Grade 3 = more than 50% of the surface
Time frame: Baseline, 12 months (Day 364) and 24 months (Day 728)
Population: Intention-To-Treat
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Chondroitin Sulfate (Condrosan) | Bone Marrow Lesions Score | Global Knee - Visit 2 (Baseline) | 2.57 units on a scale | Standard Deviation 3.04 |
| Chondroitin Sulfate (Condrosan) | Bone Marrow Lesions Score | Global Knee - Visit 6 (Day 364) | 3.16 units on a scale | Standard Deviation 3.53 |
| Chondroitin Sulfate (Condrosan) | Bone Marrow Lesions Score | Global Knee - Visit 9 (Day 728) | 3.58 units on a scale | Standard Deviation 3.68 |
| Celecoxib (Celebrex) | Bone Marrow Lesions Score | Global Knee - Visit 2 (Baseline) | 2.65 units on a scale | Standard Deviation 2.51 |
| Celecoxib (Celebrex) | Bone Marrow Lesions Score | Global Knee - Visit 6 (Day 364) | 2.77 units on a scale | Standard Deviation 2.4 |
| Celecoxib (Celebrex) | Bone Marrow Lesions Score | Global Knee - Visit 9 (Day 728) | 3.37 units on a scale | Standard Deviation 2.83 |
Secondary
Cartilage Volume in the Medial Compartment
To compare the cartilage volume loss of the medial compartment at the Baseline visit and after 12 and 24 months.
Time frame: 12 months (Day 364) and 24 months (Day 728)
Population: Intention-To-Treat
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Chondroitin Sulfate (Condrosan) | Cartilage Volume in the Medial Compartment | Visit 6 (Day 364) | 5793 cubic milimeters | Standard Deviation 83 |
| Chondroitin Sulfate (Condrosan) | Cartilage Volume in the Medial Compartment | Visit 9 (Day 728) | 5672 cubic milimeters | Standard Deviation 87 |
| Celecoxib (Celebrex) | Cartilage Volume in the Medial Compartment | Visit 6 (Day 364) | 5586 cubic milimeters | Standard Deviation 84 |
| Celecoxib (Celebrex) | Cartilage Volume in the Medial Compartment | Visit 9 (Day 728) | 5439 cubic milimeters | Standard Deviation 87 |
Secondary
Cartilage Volume Loss of the Global Knee
To compare the cartilage volume loss of the global knee at the Baseline visit and after 12 and 24 months.
Time frame: 12 months (Day 364) and 24 months (Day 728)
Population: Intention-to-Treat
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Chondroitin Sulfate (Condrosan) | Cartilage Volume Loss of the Global Knee | Visit 6 (Day 364) | 12210 cubic milimeters | Standard Deviation 175 |
| Chondroitin Sulfate (Condrosan) | Cartilage Volume Loss of the Global Knee | Visit 9 (Day 728) | 11877 cubic milimeters | Standard Deviation 179 |
| Celecoxib (Celebrex) | Cartilage Volume Loss of the Global Knee | Visit 6 (Day 364) | 11770 cubic milimeters | Standard Deviation 175 |
| Celecoxib (Celebrex) | Cartilage Volume Loss of the Global Knee | Visit 9 (Day 728) | 11572 cubic milimeters | Standard Deviation 179 |
Secondary
Percentage of Participants With Presence of Joint Swelling and Effusion
Study knees were evaluated at each visit for the presence or absence of swelling and effusion.
Time frame: Baseline, 12 months (Day 364) and 24 months (Day 728)
Population: Intention-To-Treat
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Chondroitin Sulfate (Condrosan) | Percentage of Participants With Presence of Joint Swelling and Effusion | Baseline | 60.8 percentage of participants |
| Chondroitin Sulfate (Condrosan) | Percentage of Participants With Presence of Joint Swelling and Effusion | Visit 9 (Day 728) | 10.3 percentage of participants |
| Celecoxib (Celebrex) | Percentage of Participants With Presence of Joint Swelling and Effusion | Baseline | 56.7 percentage of participants |
| Celecoxib (Celebrex) | Percentage of Participants With Presence of Joint Swelling and Effusion | Visit 9 (Day 728) | 17.7 percentage of participants |
Secondary
Percentage of Participants With the Presence of Extrusion in the Meniscus
The presence of a meniscal extrusion was assessed in each of sub regions. The absence of a severe extrusion in all the sub regions was considered as an absence (score=0) of a severe extrusion in the meniscus. The presence of a severe extrusion in at least one region of the meniscus was sufficient to consider the presence (score=1) of a severe extrusion in the meniscus.
Time frame: Baseline, 12 months (Day 364) and 24 months (Day 728)
Population: Intention-To-Treat
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Chondroitin Sulfate (Condrosan) | Percentage of Participants With the Presence of Extrusion in the Meniscus | Visit 2 (Baseline) Medial meniscus | 47.4 percentage of participants |
| Chondroitin Sulfate (Condrosan) | Percentage of Participants With the Presence of Extrusion in the Meniscus | Visit 6 (Day 364) Medial meniscus | 53.6 percentage of participants |
| Chondroitin Sulfate (Condrosan) | Percentage of Participants With the Presence of Extrusion in the Meniscus | Visit 9 (Day 728) Medial meniscus | 56.1 percentage of participants |
| Chondroitin Sulfate (Condrosan) | Percentage of Participants With the Presence of Extrusion in the Meniscus | Visit 2 (Baseline) Lateral meniscus | 6.2 percentage of participants |
| Chondroitin Sulfate (Condrosan) | Percentage of Participants With the Presence of Extrusion in the Meniscus | Visit 6 (Day 364) Lateral meniscus | 7.2 percentage of participants |
| Chondroitin Sulfate (Condrosan) | Percentage of Participants With the Presence of Extrusion in the Meniscus | Visit 9 (Day 728) Lateral meniscus | 8.8 percentage of participants |
| Celecoxib (Celebrex) | Percentage of Participants With the Presence of Extrusion in the Meniscus | Visit 6 (Day 364) Lateral meniscus | 2.9 percentage of participants |
| Celecoxib (Celebrex) | Percentage of Participants With the Presence of Extrusion in the Meniscus | Visit 2 (Baseline) Medial meniscus | 47.4 percentage of participants |
| Celecoxib (Celebrex) | Percentage of Participants With the Presence of Extrusion in the Meniscus | Visit 2 (Baseline) Lateral meniscus | 3.1 percentage of participants |
| Celecoxib (Celebrex) | Percentage of Participants With the Presence of Extrusion in the Meniscus | Visit 6 (Day 364) Medial meniscus | 53.6 percentage of participants |
| Celecoxib (Celebrex) | Percentage of Participants With the Presence of Extrusion in the Meniscus | Visit 9 (Day 728) Lateral meniscus | 3.2 percentage of participants |
| Celecoxib (Celebrex) | Percentage of Participants With the Presence of Extrusion in the Meniscus | Visit 9 (Day 728) Medial meniscus | 60.3 percentage of participants |
Secondary
Short Form (SF-36) Health Survey
The SF-36 is composed of 35 items measuring: * 8 health concepts (or dimensions), \[(Physical Functioning (PF), Role Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role Emotional (RE) and Mental Health (MH)\] * and 1 reported health transition item. The 8 health concepts are summarized in 1 physical (PCS) and 1 mental (MCS) component summary measures. PCS is represented by physical function, role limitations-physical, pain, and general health perception. MCS is represented by vitality, social function, role limitations-emotional, and mental health. Subscale items are summed and scaled from 0-100 to give subscale scores; 0= worst health related quality of life (HRQL), 100=best HRQL. PCS and MCS summary scores are constructed as T-scores (mean =50, standard deviation=10) with no minimum or maximum score; higher scores indicate better health status.
Time frame: Baseline, 12 months (Day 364) and 24 months (Day 728)
Population: Intention-To-Treat
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Chondroitin Sulfate (Condrosan) | Short Form (SF-36) Health Survey | Visit 2 (Baseline) Physical Component Summary | 35.4 Scores on a scales | Standard Deviation 7.8 |
| Chondroitin Sulfate (Condrosan) | Short Form (SF-36) Health Survey | Visit 6 (Day 364) Physical Component Summary | 39.6 Scores on a scales | Standard Deviation 9.6 |
| Chondroitin Sulfate (Condrosan) | Short Form (SF-36) Health Survey | Visit 9 (Day 728) Physical Component Summary | 41.8 Scores on a scales | Standard Deviation 9.5 |
| Chondroitin Sulfate (Condrosan) | Short Form (SF-36) Health Survey | Visit 2 (Baseline) Mental Component Summary | 51.7 Scores on a scales | Standard Deviation 9.5 |
| Chondroitin Sulfate (Condrosan) | Short Form (SF-36) Health Survey | Visit 6 (Day 364) Mental Component Summary | 53.2 Scores on a scales | Standard Deviation 9 |
| Chondroitin Sulfate (Condrosan) | Short Form (SF-36) Health Survey | Visit 9 (Day 728) Mental Component Summary | 52.7 Scores on a scales | Standard Deviation 9.2 |
| Celecoxib (Celebrex) | Short Form (SF-36) Health Survey | Visit 6 (Day 364) Mental Component Summary | 54.0 Scores on a scales | Standard Deviation 10.7 |
| Celecoxib (Celebrex) | Short Form (SF-36) Health Survey | Visit 2 (Baseline) Physical Component Summary | 35.7 Scores on a scales | Standard Deviation 8.1 |
| Celecoxib (Celebrex) | Short Form (SF-36) Health Survey | Visit 2 (Baseline) Mental Component Summary | 52.7 Scores on a scales | Standard Deviation 11 |
| Celecoxib (Celebrex) | Short Form (SF-36) Health Survey | Visit 6 (Day 364) Physical Component Summary | 41.6 Scores on a scales | Standard Deviation 10.1 |
| Celecoxib (Celebrex) | Short Form (SF-36) Health Survey | Visit 9 (Day 728) Mental Component Summary | 56.0 Scores on a scales | Standard Deviation 8 |
| Celecoxib (Celebrex) | Short Form (SF-36) Health Survey | Visit 9 (Day 728) Physical Component Summary | 42.2 Scores on a scales | Standard Deviation 10 |
Secondary
Synovial Fluid Volume
To compare the synovial fluid volume of the global knee at the Baseline visit and after 24 months.
Time frame: Baseline, 12 months (Day 364) and 24 months (Day 728)
Population: Intention-To-Treat
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Chondroitin Sulfate (Condrosan) | Synovial Fluid Volume | Visit 2 (Baseline) | 13.83 mililiters | Standard Deviation 14.61 |
| Chondroitin Sulfate (Condrosan) | Synovial Fluid Volume | Visit 6 (Day 364) | 10.30 mililiters | Standard Deviation 10.08 |
| Chondroitin Sulfate (Condrosan) | Synovial Fluid Volume | Visit 9 (Day 728) | 10.97 mililiters | Standard Deviation 14.52 |
| Celecoxib (Celebrex) | Synovial Fluid Volume | Visit 2 (Baseline) | 10.79 mililiters | Standard Deviation 10.94 |
| Celecoxib (Celebrex) | Synovial Fluid Volume | Visit 6 (Day 364) | 9.49 mililiters | Standard Deviation 12.06 |
| Celecoxib (Celebrex) | Synovial Fluid Volume | Visit 9 (Day 728) | 9.07 mililiters | Standard Deviation 13.6 |
Secondary
Synovial Membrane Thickness
To compare the severity of synovitis score (Thickness of the Synovial Membrane in mm) in Global Knee , at the baseline visit and the follow-up visits in subjects treated either with CHONDROITIN SULPHATE (CONDROSAN) or CELECOXIB. The severity of synovitis was evaluated through four regions of interest (ROIs) in the images of the axial T1-weighted acquisition complemented with the use of the images of the axial T2-weighted acquisition. The thickness of the synovial membrane was evaluated in the global knee and each of the ROIs and results were expressed in millimetres. The four ROIs were the proximal lateral, distal lateral, proximal medial and distal medial.
Time frame: Baseline, 12 months (Day 364) and 24 months (Day 728)
Population: Intention-To-Treat
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Chondroitin Sulfate (Condrosan) | Synovial Membrane Thickness | Visit 2 (Baseline) | 0.99 milimeters | Standard Deviation 0.22 |
| Chondroitin Sulfate (Condrosan) | Synovial Membrane Thickness | Visit 6 (Day 364) | 1.05 milimeters | Standard Deviation 0.22 |
| Chondroitin Sulfate (Condrosan) | Synovial Membrane Thickness | Visit 9 (Day 728) | 1.19 milimeters | Standard Deviation 0.26 |
| Celecoxib (Celebrex) | Synovial Membrane Thickness | Visit 2 (Baseline) | 0.96 milimeters | Standard Deviation 0.22 |
| Celecoxib (Celebrex) | Synovial Membrane Thickness | Visit 6 (Day 364) | 1.07 milimeters | Standard Deviation 0.26 |
| Celecoxib (Celebrex) | Synovial Membrane Thickness | Visit 9 (Day 728) | 1.16 milimeters | Standard Deviation 0.31 |
Secondary
Use of Acetaminophen
Consumption of Acetaminophen: At each post-baseline visit, the investigator had to assess the consumption of acetaminophen, rescue analgesic authorised throughout the study, by reporting the number of caplets dispensed/retrieved since the previous visit. Daily consumption of acetaminophen was calculated as an average.
Time frame: 3 months (Day 91), 6 momnths (Day 182), 12 months (Day 364), 18 monts (Day 546) and 24 months (Day 728)
Population: Intention-To-Treat
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Chondroitin Sulfate (Condrosan) | Use of Acetaminophen | 1.17 Daily number of caplets taken | Standard Deviation 1.43 |
| Celecoxib (Celebrex) | Use of Acetaminophen | 0.94 Daily number of caplets taken | Standard Deviation 1.61 |
Secondary
Visual Analog Scale (VAS)
Visual Analogue Scale: 0 No Pain 10 Maximum Pain Huskisson's VAS measures global pain intensity. Patients were asked to quantify their disease status on a 10 cm VAS as follows: Please indicate the severity of knee pain experienced during the last 48 hours by marking a (I) through the line. Left hand marker represents No pain and right hand marker represents The worst pain imaginable.
Time frame: Baseline, 12 months (Day 364) and 24 months (Day 728)
Population: Intention-To-Treat
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Chondroitin Sulfate (Condrosan) | Visual Analog Scale (VAS) | Visit 2 (Baseline) | 6.24 centimeters | Standard Deviation 1.55 |
| Chondroitin Sulfate (Condrosan) | Visual Analog Scale (VAS) | Visit 6 (Day 364) | 3.43 centimeters | Standard Deviation 2.6 |
| Chondroitin Sulfate (Condrosan) | Visual Analog Scale (VAS) | Visit 9 (Day 728) | 3.12 centimeters | Standard Deviation 2.85 |
| Celecoxib (Celebrex) | Visual Analog Scale (VAS) | Visit 2 (Baseline) | 5.93 centimeters | Standard Deviation 1.81 |
| Celecoxib (Celebrex) | Visual Analog Scale (VAS) | Visit 6 (Day 364) | 3.02 centimeters | Standard Deviation 2.51 |
| Celecoxib (Celebrex) | Visual Analog Scale (VAS) | Visit 9 (Day 728) | 2.45 centimeters | Standard Deviation 2.33 |
Secondary
WOMAC Function Subscale
Western Ontario & McMaster Universities Osteoarthritis Index, from 0 No Function to 170 Maximum Function WOMAC functional limitation subscale was used to measure the functionality of the knee with pain. Seventeen items are used to assess functionality of the knee: tair use, rising from sitting, standing, bending, walking, getting in / out of a car, shopping, putting on / taking off socks, rising from bed, lying in bed, getting in / out of bath, sitting, getting on / off toilet, heavy household duties, light household duties. Each item is a 10 cm VAS with 0 and 10 cm representing no difficulty and extreme difficulty respectively.
Time frame: Baseline, 12 months (Day 364) and 24 months (Day 728)
Population: Intention-To-Treat
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Chondroitin Sulfate (Condrosan) | WOMAC Function Subscale | Visit 2 (Baseline) | 88.5 centimeters | Standard Deviation 28.7 |
| Chondroitin Sulfate (Condrosan) | WOMAC Function Subscale | Visit 6 (Day 364) | 52.3 centimeters | Standard Deviation 39.1 |
| Chondroitin Sulfate (Condrosan) | WOMAC Function Subscale | Visit 9 (Day 728) | 50.0 centimeters | Standard Deviation 44.4 |
| Celecoxib (Celebrex) | WOMAC Function Subscale | Visit 9 (Day 728) | 46.2 centimeters | Standard Deviation 41.4 |
| Celecoxib (Celebrex) | WOMAC Function Subscale | Visit 2 (Baseline) | 89.5 centimeters | Standard Deviation 32.5 |
| Celecoxib (Celebrex) | WOMAC Function Subscale | Visit 6 (Day 364) | 51.0 centimeters | Standard Deviation 42.7 |
Secondary
WOMAC Pain Subscale
Western Ontario & McMaster Universities Osteoarthritis Index (WOMAC) Pain subscale Score Range: 0 (no pain) - 50 (maximum pain) The study was designed such that the outcome of primary interest is knee pain related to OA. The measure selected to best evaluate this is an improvement in the WOMAC pain subscales. This subscale consists of 5 items which assesses the pain during walking, using stairs, in bed, sitting or lying, and standing.Each item is a 10 cm VAS with 0 and 10 cm representing no pain and extreme pain respectively.
Time frame: Baseline, 12 months (Day 364) and 24 months (Day 728)
Population: Intention-To-Treat
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Chondroitin Sulfate (Condrosan) | WOMAC Pain Subscale | Visit 2 (Baseline) | 25.6 centimeters | Standard Deviation 8.11 |
| Chondroitin Sulfate (Condrosan) | WOMAC Pain Subscale | Visit 6 (Day 364) | 14.71 centimeters | Standard Deviation 11.55 |
| Chondroitin Sulfate (Condrosan) | WOMAC Pain Subscale | Visit 9 (Day 728) | 13.51 centimeters | Standard Deviation 12.67 |
| Celecoxib (Celebrex) | WOMAC Pain Subscale | Visit 2 (Baseline) | 25.51 centimeters | Standard Deviation 9.04 |
| Celecoxib (Celebrex) | WOMAC Pain Subscale | Visit 6 (Day 364) | 13.62 centimeters | Standard Deviation 11.49 |
| Celecoxib (Celebrex) | WOMAC Pain Subscale | Visit 9 (Day 728) | 10.69 centimeters | Standard Deviation 10.66 |
Secondary
WOMAC Stiffness Subscale
Western Ontario & McMaster Universities Osteoarthritis Index, from 0 No Stiffness to 20 Maximum Stiffness WOMAC stiffness subscale was used to measure the stiffness of the knee with pain. Two items are used to assess stiffness grade: after first waking and later in the day.Each item is a 10 cm VAS with 0 and 10 cm representing no difficulty and extreme difficulty respectively.
Time frame: Baseline, 12 months (Day 364) and 24 months (Day 728)
Population: Intention-To-Treat
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Chondroitin Sulfate (Condrosan) | WOMAC Stiffness Subscale | Visit 2 (Baseline) | 10.76 centimeters | Standard Deviation 3.68 |
| Chondroitin Sulfate (Condrosan) | WOMAC Stiffness Subscale | Visit 6 (Day 364) | 6.53 centimeters | Standard Deviation 4.76 |
| Chondroitin Sulfate (Condrosan) | WOMAC Stiffness Subscale | Visit 9 (Day 728) | 6.15 centimeters | Standard Deviation 5.27 |
| Celecoxib (Celebrex) | WOMAC Stiffness Subscale | Visit 2 (Baseline) | 11.65 centimeters | Standard Deviation 4.25 |
| Celecoxib (Celebrex) | WOMAC Stiffness Subscale | Visit 6 (Day 364) | 6.60 centimeters | Standard Deviation 5.31 |
| Celecoxib (Celebrex) | WOMAC Stiffness Subscale | Visit 9 (Day 728) | 5.44 centimeters | Standard Deviation 5.28 |