Condrosulf vs Celebrex vs Placebo in the Treatment of Knee OA

Study Overview
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Brief Summary
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The purpose of this study is to confirm the efficacy and safety of 800 mg Chondroitin 4&6 sulfate (Condrosulf) vs placebo once a day for 6 months in the symptomatic treatment of knee osteoarthritis. A third group, Celecoxib 200 mg (Celebrex) once a day, will be used as active comparator.

Official Title
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A Multicentre, Comparative, Randomised, Double-blind, Double-dummy Clinical Trial on the Efficacy and Safety of Condrosulf Versus Celebrex and Versus a Placebo in the Treatment of Knee Osteoarthritis

Conditions
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Knee Osteoarthritis

Intervention / Treatment
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* Drug: chondroitin sulfate
* Drug: celecoxib
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Outpatients of either sex, aged ≥50 years Patients affected by primary knee osteoarthritis of the medial or lateral femoro-tibial compartment Diagnosis according to the American College of Rheumatology (ACR) criteria Kellgren & Lawrence grade I-III Knee osteoarthritis evolving for more than 6 months Patients suffering from regular pain and functional disorders from at least 3 months Accomplishing a score ≥ 7 of Lequesne's index for the knee osteoarthritis Assessing pain on Huskisson's VAS ≥ 50 mm With radiography dated less than six months showing a remaining articular joint space Without such an axial disorder to justify an osteotomy Women taking contraceptive measures if not in menopause Women having negative pregnancy test Patients able to understand and follow the study protocol Patients who have signed the written informed consent for their participation in the clinical trial Exclusion Criteria: With a history of heart attack, ischemic heart disease or cerebrovascular disease (including transient ischemic attacks) Having or have had peripheral arterial disease or past surgery orf peripheral arteries With a history or currently significat coagulation defect or/and blood dyscrasia With high risk of cardiovascular events With any acute or chronic infections requiring antimicrobial therapy or serious viral (e.g., hepatitis, HIV positivity) or fungal infections With a history of recurrent gastrointestinal ulceration or active inflammatory bowel diseases (e.g., Crohn's disease or ulcerative colitis) Having 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 Having severe liver or kidney disease With allergy to Celebrex or any of the other ingredients of Celebrex Having had an allergic reaction to sulphonamides Having had, as a result of intake of acetylsalicylic acid or other NSAIDs, asthma, nose polyps, severe nose congestion, or an allergic reaction such as itchy skin rash, swelling of the face, lips, tongue or throat, breathing difficulties or wheezing Presenting lactose intolerance Mild or not symptomatic knee osteoarthritis : < 7 of Lequesne's index, Pain on Huskisson's VAS (Visual Analogic Scale) < 50 mm Predominantly femoro-patellar osteoarthritis Destructive osteoarthritis of the knee justifying a surgery in the following 6 months Osteoarthritis with hydrarthrosis requiring a puncture or an infiltration Important genu varum or valgus >8° (physiological angle including) Kellgren & Lawrence grade IV Knee joint surgery in the last 3 months (e.g. chondroscopy, arthroscopy) Viscosupplementation, tidal lavage in the last 6 months Arthritis and metabolic arthropathies, Paget's illness Having consumed: basic treatment of arthritis with SYSADOA, symptomatic slow acting drugs for osteoarthrithis (chondroitin sulphates, glucosamine sulphates, diacerhein, hyaluronic acid and food supplement for joint care) in the last 3 months; treatment with corticoids, by any administration route during the last month; any medication having an influence on pain: NSAIDs (nonsteroidal anti-inflammatory drugs) in the 5 days preceding the inclusion (wash-out period considering 5 half-lives of the drug) hypnotics, muscle relaxants, anxiolytics, if the intake has started less than 8 days before inclusion paracetamol in the 10 hours preceding the inclusion Foreseen physiotherapy, re-education, alternative medicine (mesotherapy, acupuncture) in the next six months (study period) Presenting psychiatric illness hindering the protocol complaince, alcoholism, ongoing or < 1 year drug dependency Pregnant or likely to become it during clinical trial or lactating Women having positive pregnancy test Having participated in other clinical trials in the month preceding the clinical trial.

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Condrosulf (Chondroitin 4&6 sulfate)<br>1 tablet of Condrosulf 800 mg and 1 capsule of placebo of Celebrex once a day for 182 days | Drug: chondroitin sulfate<br> <br> * Other names: Condrosulf;|
| Placebo Comparator: Placebo (PBO) 800 mg tablet and Placebo (PBO) 200 mg capsule<br>1 tablet of PBO of Condrosulf and 1 capsule of PBO of Celebrex, once a day for 182 days | Drug: placebo<br> <br> * Other names: placebo for chondroitin sulfate and placebo for celecoxib;|
| Active Comparator: Celebrex 200 mg capsule<br>1 capsule of 200 mg of Celebrex and 1 tablet of 800 mg placebo of Condrosulf once a day for 182 days | Drug: celecoxib<br> <br> * Other names: Celebrex;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Lequesne's Index | Decrease in the scores of the Lequesne's Index from Day 1 to Day 182. | Day 1 and Day 182 | 
| Pain (VAS in mm) | Decrease in the VAS (pain in mm) from Day 1 to Day 182 | Day 1 and Day 182 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Lequesne's Index | Evolution from Day 1 to Day 30, Day 90 and Day 182 | Day 1, 30, 90 and 182 | 
| Pain (VAS in mm) | Evolution of the pain on VAS (in mm) from Day 1 to Day 30, Day 91 and Day 182 | Day 1, 30, 91 and 182 | 
| MCII (minimal clinically important improvement) |  | Day 1, 30, 91 and 182 | 
| PASS (patient acceptable symptom state) |  | Day 1, 30, 91 and 182 | 
| Consumption of Paracetamol |  | Day 1, 30, 91 and 182 | 
| Global efficacy assessment | Global efficacy assessed by the patient and the Investigator by means of a semi-quantitative verbal scale. | At Day 30, 91 and 182 | 
| Number of adverse events related to the treatments |  | At Day 30, 91 and 182 | 
| Number of drop-outs due to AE (adverse event) related to the treatment |  | At Day 30, 91 and 182 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Condrosulf, Chondroitin sulfate, Celebrex, Knee OA, Knee osteoarthritis