Study on Efficacy and Safety of Chondroitin Sulfate + Glucosamine Hydrochloride Versus Celecoxib in Knee Osteoarthritis

Study Overview
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Brief Summary
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The purpose of this study is to determine whether the combination of Chondroitin sulfate (CS) and Glucosamine Hydrochloride (GH) has similar efficacy to Celecoxib (CE) in the treatment of patients with moderate to severe knee osteoarthritis (OA).

Detailed Description
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The primary objective of this study is to show that the combination treatment CS/GH has comparable efficacy to CE in pain reduction from baseline to 6 months of treatment measured with the Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain subscale in knee OA patients with moderate to severe pain.

Official Title
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Non-Inferiority Clinical Trial On The Efficacy And Safety Of Chondroitin Sulfate And Glucosamine Hydrochloride In Combination Versus Celecoxib In Patients With Knee Osteoarthritis

Conditions
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Knee Osteoarthritis

Intervention / Treatment
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* Drug: Chondroitin/Glucosamine (Droglican)
* Drug: Celecoxib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: At least 40 years of age Primary OA of the knee according to the American College of Rheumatology (ACR) criteria OA of radiological stages II or III according to Kellgren and Lawrence Patients with moderate-severe knee pain Exclusion Criteria: Subjects with active malignancy of any type or history of a malignancy within the last five years Concurrent arthritic disease (antecedents and/or current signs) that could confound or interfere with the evaluation of pain efficacy 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 Pain in other parts of the body greater than the knee pain that could interfere with the evaluation of the index joint Patients with fibromyalgia Subjects with a history of heart attack or stroke, or who have experienced chest pain related to heart disease, or who have had serious diseases of the heart Subjects with high risk of cardiovascular (CV) events Subjects with any active acute or chronic infections requiring antimicrobial therapy, or serious viral (e.g., hepatitis, herpes zoster, HIV positivity) or fungal infections Subjects with a history of recurrent Upper Gastrointestinal (UGI) ulceration or active inflammatory bowel disease (e.g., Crohn's disease or ulcerative colitis), a significant coagulation defect Subjects who 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 Washout period for OA treatments before beginning the study.

Ages Eligible for Study
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Minimum Age: 40 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: Chondroitin/Glucosamine (Droglican)<br>Active ingredients: Chondroitin sulfate, 200 mg and Glucosamine hydrochloride 250 mg. Pharmacotherapeutic group: Other specific antirheumatic agents. Anatomical Therapeutic Chemical Classification System (ATC) code: M01CX. | Drug: Chondroitin/Glucosamine (Droglican)<br>* Experimental<br>* Other names: Chondroitin sulfate/ Glucosamine hydrochloride;|
| Active Comparator: Celecoxib<br>Active ingredient: Celecoxib, 200 mg. Pharmacotherapeutic group: Coxibs. ATC code: M01AH. | Drug: Celecoxib<br>* Active comparator<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| WOMAC Pain Subscale | Western Ontario & McMaster Universities Osteoarthritis Index (WOMAC) Pain subscale Score Range: 0 (no pain) - 500 (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. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| WOMAC Stiffness Subscale | Western Ontario & McMaster Universities Osteoarthritis Index, from 0 No Stiffness to 200 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. | 6 months | 
| WOMAC Function Subscale | Western Ontario & McMaster Universities Osteoarthritis Index, from 0 No Function to 1700 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. | 6 months | 
| Huskisson's VAS | Visual Analogue Scale: 0 No Pain 100 Maximum Pain Huskisson's VAS measures global pain intensity. Patients were asked to quantify their disease status on a 100 mm 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. | 6 months | 
| Percentage of Participants With Response as Defined by Outcome Variables for Osteoarthritis Clinical Trials - Osteoarthritis Research Society International (OMERACT-OARSI) | The OARSI Standing Committee for Clinical Trials Response Criteria Initiative and the OMERACT committee, in concert with the international rheumatology community, has led to the development of a uniform core set of outcome measures for OA. One of the objectives was to propose a set of criteria for measurement based on multiple domains to present the results of changes after treatment in symptomatic parameters as a single variable for clinical trials. To be considered as responder patients should met one the following criteria: High improvement in pain or in function ≥ 50% and absolute change ≥ 20 or Improvement in at least 2 of the 3 following: Pain ≥ 20% and absolute change ≥ 10 Function ≥ 20% and absolute change ≥ 10 Patient's global assessment ≥ 20% and absolute change ≥ 10 | 6 months | 
| Percentage of Presence of Joint Swelling | Study knees were evaluated at each visit for the presence or absence of swelling and/or effusion. | 6 months | 
| Percentage of Presence of Joint Effusion | Study knees were evaluated at each visit for the presence or absence of swelling and/or effusion. | 6 months | 
| Consumption of Rescue Medication | Use of rescue medication as number of paracetamol tablets 500 mg since the last visit. The tablet count was reconciled with the patient diary. Total Number of pills per month | 6 months | 
| Patient's Global Assessment (PGA) and Investigator's Global Assessment (IGA) of Disease Activity | Patients were asked to quantify their disease status on a VAS scale with range 0 mm (best) and 100 mm (worst) as follows: Considering all the ways your arthritis of the knee affects you, mark (I) on the scale how well you are doing. Left hand marker Very Well, Right hand marked Very Poor. | 6 months | 
| Patient's and Investigator's Global Assessment of Response to Therapy | The investigator were asked to evaluated the patient's response to therapy of the index knee by marking a (I) a VAS scale with range 0 mm (best) and 100 mm (worst) as follows: Left hand marker Excellent-Best possible anticipated response, considering the severity and stage of the disease, right hand marker None-no response, absence of drug effect. | 6 months | 
| Health Status According to EuroQoL | EuroQoL-5D was a standardized instrument for use as a measure of health outcome that provides a simple descriptive profile and a single index value for health status. It was assessed at all of the study visits. The EQ-5D-3L essentially consists of 2 pages - the EQ-5D descriptive system (page 2) and the EQ visual analogue scale (EQ VAS) (page 3). The EQ-5D-3L descriptive system comprises the following 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 3 levels: no problems, some problems, extreme problems. Total scale range for each dimension reported is 1 to 3. The EQ VAS records the respondent's self-rated health on a vertical, visual analogue scale where the endpoints are labelled 'Best imaginable health state' and 'Worst imaginable health state'. This information can be used as a quantitative measure of health outcome as judged by the individual respondents. Total scale range for VAS dimension reported is 0 to 100. | 6 months | 
| Number of Participants With at Least One Adverse Events | The safety evaluation was done in the set of randomized patients who took at least one dose of the medication | 6 months | 
| Number of Adverse Events Defined by Relationship With Treatment | The safety evaluation was done in the set of randomized patients who took at least one dose of the medication | 6 months | 
| Biomarker Analysis | The following biomarkers will be evaluated: COMP, Coll2-1, Coll2-1 NO2 and Fib3-2 | 6 months |