Efficacy of OSTENIL PLUS (Hyaluronic Acid) Versus SYNVISC-ONE in Patients With Tibiofemoral Osteoarthritis

Study Overview
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Brief Summary
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The main objective of the study was to demonstrate the non-inferiority of the efficacy of a single intra-articular injection of OSTENIL PLUS compared to that of a single intra-articular injection of the reference product SYNVISC-ONE in the treatment of symptomatic tibiofemoral osteoarthritis. The primary endpoint was the change in mean score on the WOMAC pain scales from D0 to D180.

Detailed Description
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After a period of washout-out for NSAIDs, the patients received a single intra-articular injection of OSTENIL PLUS or of SYNVISC-ONE in the most painful knee. The study involved a preselection visit at D-7 and five further visits: at D0 (baseline, evaluation before intra-articular injection), at D2 ± 2 days (injection), at D30 ± 15 days, at D90 ± 15 days and C5 at D180 ± 15 days. To enrol the patients as quickly as possible, 129 sites, i.e. general medical or rheumatology practices, were open. After verifying the inclusion and exclusion criteria, the evaluating investigators assigned a randomisation number based on the chronological order of inclusion of patients at their site. The patient was then sent to the injecting investigator so that he/she could give the injection of the product corresponding to the randomisation number.

Official Title
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Efficacy of OSTENIL PLUS (Hyaluronic Acid) Versus SYNVISC-ONE in Patients With Tibiofemoral Osteoarthritis. A Randomised, Controlled, Double-blind, Parallel-group Study With a 6-month Follow-up

Conditions
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Knee Osteoarthritis

Intervention / Treatment
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* Device: OSTENIL PLUS
* Device: SYNVISC-ONE


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female aged 40-85 years; Primary knee osteoarthritis complying with the American College or Rheumatology criteria; Radiographically defined osteoarthritis: joint space narrowing and osteophyte in X-ray taken less than one year previously and modified Kellgren-Lawrence grade Ib-III; Symptoms on one side only, with a mean WOMAC A of ≥40 mm. If knee osteoarthritis is bilateral, a difference for that score between the contralateral knee and the selected knee should be of at least 20 mm; Pain present on at least 15 days in the month before inclusion; Failure or intolerance of first line analgesics and NSAIDs; With health insurance; Understanding and following the study instructions; Signed the informed consent. Exclusion Criteria: Knee osteoarthritis that is not symptomatic or insufficiently symptomatic; Bilateral symptomatic knee osteoarthritis of the same severity on both sides; Post-traumatic secondary knee osteoarthritis; Knee osteoarthritis of radiographic grade I, Ia or IV; Exclusively patellofemoral osteoarthritis where the symptoms are principally of patellofemoral origin (Patellar syndrome); Symptomatic homolateral coxarthrosis; Varus or valgus deformation of the selected knee (deformation axis ≥15° in X-ray); Inflammatory rheumatism (rheumatoid arthritis, psoriatic rheumatism, articular chondrocalcinosis, gout, Paget's disease, ankylosing spondylitis, lupus, etc.); History of injury to the selected knee during the 6 months before inclusion; Venous or lymphatic stenosis of the lower limb; Femoral or sciatic nerve root pain of the lower limb to be tested; Tendinopathy (e.g. hip periarthritis); Treatment with intra-articular hyaluronic acid in the selected knee during the 6 months before inclusion; Intra-articular injection of corticosteroids in the selected knee during the 2 months before inclusion; Treatment with symptomatic slow-acting drugs for osteoarthritis and/or dietary supplements for osteoarthritis (chondroitin sulphate, diacerein, avocado and soybean unsaponifiables, oxaceprol, copper granions, glucosamine) which had been started less than 3 months previously or whose dose had been changed during the last 3 months before inclusion; Total knee replacement of the selected knee; Surgery of the other knee or of the hip or any other surgery scheduled during the period of the study; History of any surgical intervention, arthroscopy, osteotomy, etc. in the year before inclusion; Obesity: body mass index ≥30 kg/m2; History of autoimmune disease; Severe condition likely to interfere with the evaluation, such as neoplasia, malignant blood disease, kidney disease, liver disease or severe infection; Very marked hydrarthrosis (requiring puncture) at the time of inclusion; Wound or skin condition of the selected knee; Anticoagulant treatment with heparin or warfarin (platelet antiaggregants such as ASPIRIN ≤325 mg/d, ticlopidine or clopidogrel were allowed); Known hypersensitivity to hyaluronic acid and/or to avian proteins and/or paracetamol; Known hypersensitivity to mannitol; Participation in a clinical research study within the previous 3 months; Pregnancy, breast-feeding.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 85 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
Interventional Model Description: This study was a multicentre, prospective, double-blind, randomised, controlled non-inferiority study in two parallel groups of patients followed up for six months.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: OSTENIL PLUS<br>A single intra-articular injection of sodium hyaluronate 40 mg/2.0 ml at Day 2, i.e. 2 days post Baseline (Day 0 = Week 0) | Device: OSTENIL PLUS<br>* Injection into the joint cavity of the most painful knee<br>|
| Active Comparator: SYNVISC-ONE<br>A single intra-articular injection of hylan G-F 20 48 mg/6 ml at Day 2, i.e. 2 days post Baseline (Day 0 = Week 0) | Device: SYNVISC-ONE<br>* Injection into the joint cavity of the most painful knee<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in WOMAC A | Change from baseline in the pain subscore (section A) of the WOMAC score | Day 0 to Day 180 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Lequesne algofunctional index | Index assessing the severity of osteoarthritis | Day 0 to Day 180 | 
| WOMAC B | Stiffness subscore (section B) of the WOMAC score | Day 0 to Day 180 | 
| WOMAC C | Function subscore (section C) of the WOMAC score | Day 0 to Day 180 | 
| Patient's overall status score in relation to his/her knee osteoarthritis | Visual analogue scale assessed by the patient | Day 0 to Day 180 | 
| Assessment of overall treatment efficacy by the patient | 5-point scale (1 = very good; 2 = good; 3 = moderate; 4 = poor; 5 = very poor) | Day 30 to Day 180 | 
| Assessment of overall treatment efficacy by the investigator | 5-point scale (1 = very good; 2 = good; 3 = moderate; 4 = poor; 5 = very poor) | Day 30 to Day 180 |