Efficacy and Safety of Intraarticular Sodium Hyaluronate Single Injection in Patients With Osteoarthritis of the Knee

Study Overview
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Brief Summary
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A Phase III, prospective, multicentre, non-controlled, with consecutive participant enrollment in order to evaluate the efficacy, safety and duration of the effects of the viscosupplementation with a preparation of sodium hyaluronate 2% (SH2%) from Tedec-Meiji Farma S.A. over 12 months. Adult patients diagnosed with primary osteoarthritis of the knee according to American College of Rheumatology (ACR) criteria with radiological grades II and III according to Kellgren-Lawrence scale (KL) will receive a single injection of SH2% and will be followed for 1 year with follow up visits at 6 and 12 months. At 6 months patients could be offered a second injection whenever and when they comply with the criteria established for re-treatment and will be followed for additional 6 months

Detailed Description
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Prospective, multicentre and non-controlled study. Each patient will receive a single injection of SH 2% and will be followed for 1 year with follow up visits at 6 and 12 months At 6 months follow up visit patients will be offered a second injection whenever and when they comply with the criteria established for re-treatment and will be followed for additional 6 months From the pre-inclusion V0 up to the V1 (beginning of treatment), there will be a wash-out period of 2 weeks during which only paracetamol will be allowed for osteoarthritis (OA) pain relief (maximum dose allowed:3g/day). Paracetamol will be discontinued at least 24h before follow up visits (Treatment administration, 6 months of follow up and 12 months of follow up). Clinical evaluation will be done every visits through VAS, WOMAC and Patient's Global Assessment/ Investigator's Global Assessment (PGA/IGA)

Official Title
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Prospective, Multicentre Study to Evaluate the Efficacy and Safety of Intraarticular Sodium Hyaluronate Single Injection in Patients Suffering From Osteoarthritis of the Knee

Conditions
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Osteoarthritis, Knee

Intervention / Treatment
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* Device: Sodium hyaluronate 2%


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient ≥ 45 years of age of either sex. Primary knee OA of the medial or lateral femoro-tibial compartment documented according to ACR criteria with symptoms, at screening, from at least 3 months. KL radiological grade 2-3. Antero-posterior view X-Ray image of the target knee Pain intensity at screening in the target knee ≥40 mm and <80 mm measured by Visual Analogue Scale (VAS), and ≤ 20 mm in the contralateral knee. Able to understand and willing to comply with study procedures. Able to provide informed consent. Exclusion Criteria: BMI ≥ 30 kg/m2. Pregnant or lactating women. Women of child-bearing age not using effective contraception. Severe inflammation of the target knee. Previous surgery in the target knee, including arthroscopy. Subjects with any musculoskeletal condition affecting the target knee that would impair the proper evaluation Patients with joint inflammatory disease, microcrystalline arthropathies and significant osteoarthritis symptoms in other joints apart from the knee, and which require pharmacological treatment. Underlying disease considered by the investigator that might interfere with the development and evaluation study. Subjects with venous or lymphatic stasis in the relevant limb. Previous administration of any of the following treatments: hyaluronic acid i.a. (last year); steroids i.a. or joint lavage (last 3 months), glucosamine sulfate, chondroitin sulfate or diacerein (last 3 months), NSAIDs (last 14 days), any investigational drug (last month) or its administration during this study. Pain in other parts of the body greater than the knee pain that could interfere with the evaluation. Any pathology that, under investigator judgement, interfere with the administration or assessment. Patients with known hypersensitivity to SH or paracetamol. Patients in waiting list for surgery. Patients awaiting disablement assessment. Previous participation in this protocol

Ages Eligible for Study
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Minimum Age: 45 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental: Sodium Hyaluronate 2%<br>Each patient will receive a single injection of SH2% | Device: Sodium hyaluronate 2%<br>* Each patient will receive a single injection of SH 2% and will be followed for 6 months. At 6 months follow up visit patients could be offered a second injection whenever and when they comply with the criteria established for re-treatment and will be followed for additional 6 months.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in pain intensity according to VAS (0-100mm) | The VAS to be used in the study consists of a horizontal line marked from 0 to 100 mm, where 0 means no pain and 100 is the greatest possible pain. Patients must draw a vertical line at the point that they believe that represents the pain intensity at that time. | 6 and 12 months after treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in function from baseline in the target knee | Physical function will be measured by using the function subscale of the Western Ontario & McMaster Universities Osteoarthritis Index (WOMAC). This index contains 24 items on different activities of daily life grouped in three subscales: pain (5 items), stiffness (2 items), and functional capacity (17 items). For each item a horizontal visual analogue scale of 0 to 100 mm with end descriptors is used, whose path goes from no pain, no stiffness, no difficulty to extreme pain, extreme stiffness, extreme difficulty. | 6 and 12 months after treatment | 
| Change in function from baseline in the target knee | Physical function will be measured by using the function subscale of the Western Ontario & McMaster Universities Osteoarthritis Index (WOMAC). This subscale contains 24 items on different activities of daily life grouped in three dimensions: pain, stiffness, and functional capacity. For each item a horizontal visual analogue scale of 0 to 100 mm with end descriptors is used, whose path goes from no pain, no stiffness, no difficulty to extreme pain, extreme stiffness, extreme difficulty function subscale | 6 and 12 months after treatment | 
| Percentage of patients achieving the Minimally Clinical Important Improvement (MCII) | The MCII is the smallest change in measurement that signifies an important improvement in a patient's symptom | 6 and 12 months after treatment | 
| Percentage of patients achieving the Patient Acceptable Symptoms State (PASS) | Defined as the value beyond which patients consider themselves well. According to the literature the recommended value for PASS (measured on 0-100 VAS) is < 40. | 6 and 12 months after treatment | 
| Patient and investigator global assessments | Both will be measured using a 5-point Likert scale. This is a five-level classification scale (0= Better, 1 = best, 2 = same, 3 = worst, 4 = much worse) | 6 and 12 months after treatment |