Effectiveness of Two Hyaluronic Acids in Osteoarthritis of the Knee

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to assess whether a single injection hyaluronic acid (HA) product is not inferior to a 3 injection HA product at 24 weeks (6 months), in terms of effectiveness in reducing pain when walking in patients suffering from symptomatic tibiofemoral osteoarthritis of the knee.

Detailed Description
-----------------
non-inferiority study of two HA products commercially availalble

Official Title
-----------------
Single-blind Randomised Pragmatic Trial Comparing the Effectiveness of Two Hyaluronic Acid Viscosupplements, DUROLANE® (Single Injection) Versus HYALGAN® (Three Injections) for Symptomatic Tibiofemoral Osteoarthritis of the Knee.

Conditions
-----------------
Knee Osteoarthritis

Intervention / Treatment
-----------------
* Device: 3ml hyaluronic acid (DUROLANE)
* Device: 2ml hyaluronic acid, (HYALGAN)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age ≥ 40 and < 85 Tibiofemoral osteoarthritis of the knee according to the American College of Rheumatology clinical criteria, in the Kellgren-Lawrence (KL) stages II-III, confirmed by radiology (< 3 months) Unilateral symptomatic osteoarthritis of the knee causing pain when walking (WOMAC A1 scale), assessed over the previous 24 hours on a scale of 0 to 10: Pain when walking: ≤ 3 and < 8 Bilateral osteoarthritis of the knee, if pain in the other knee is < 3 (10-point numerical scale) Patient: outpatient, capable of walking 50 metres without a walking stick, crutches or a walker, capable of reading, understanding, signing and dating the patient information sheet Patient with social security cover Exclusion Criteria: Osteoarthritis of the knee in Kellgren-Lawrence (KL) stages I and IV Bilateral symptomatic osteoarthritis of the knee causing pain when walking (WOMAC A1 scale), assessed on a scale of 0 to 10: Pain when walking > 3, in both knees Predominant symptomatic patellofemoral osteoarthritis of the knee Congestive manifestation of osteoarthritis of the knee defined according to the Knee Osteoarthritis Flare-Ups Score (KOFUS) criteria Last viscosupplementation of the affected knee < 6 months before, last injection of corticosteroids < 2 months before Known hypersensitivity to avian proteins and hyaluronic acids; History of joint replacement or major surgery in the affected knee in the last six months History of arthroscopy or surgery in the affected knee in the last three months Symptomatic hip disease on the same side or other side of the body Joint replacement or any other surgery planned in the next six months History of septic arthritis of the affected knee Skin complaint affecting the knee at the injection site Haemorrhagic disease contraindicating, in the doctor's opinion, any intra-articular injection In order to respect the pragmatic nature of the study: Any medical and / or pathological condition that, in the investigator's opinion, makes the subject unsuitable for inclusion Any medical and / or pathological condition that, in the investigator's opinion, would be a contraindication for an intra-articular injection Any other complaint that, in the investigator's opinion, would impede the assessment of the effectiveness of the affected knee Any treatment administered to the patient that may interfere with the interpretation of the study results Use of glucocorticosteroids (except inhaled corticosteroids) during the previous month Treatment with diacerein, avocado and soya unsaponifiables, glucosamine sulphate or chondroitin sulphate, started in the previous 3 months, or irregular doses over the previous 3 months Hard of hearing (not being able to follow a telephone conversation properly) Patient without a telephone Pregnant women or nursing mothers Participation in other clinical studies, within 30 days before inclusion

Ages Eligible for Study
-----------------
Minimum Age: 40 Years
Maximum Age: 85 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Single injection hyaluronic acid<br>3ml hyaluronic acid (DUROLANE) | Device: 3ml hyaluronic acid (DUROLANE)<br>* DUROLANE Hyaluronic acid 20mg/ml<br>|
| Active Comparator: Three injection hyaluronic acid<br>2ml hyaluronic acid (HYALGAN) | Device: 2ml hyaluronic acid, (HYALGAN)<br>* HYALGAN Hyaluronic acid 10mg/ml<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patients assessment of WOMAC A1 pain when walking |  | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patients assessment of WOMAC A pain |  | 24 weeks | 
| Patients assessment of WOMAC C function |  | 24 weeks | 
| Patient global assessment |  | 24 weeks | 
| OMERACT-OARSI responder rate |  | 24 weeks | 
| Patient Acceptable Symptom State (PASS) |  | 24 weeks | 
| Minimal Clinically Important Improvement (MCII) |  | 24 weeks | 
| Adverse events observed or spontaneously reported by patients for each treatment |  | 24 weeks |