Clinical trial NCT03203408: Efficacy of OSTENIL PLUS (Hyaluronic Acid) Versus SYNVISC-ONE in Patients With Tibiofemoral Osteoarthritis
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Knee Osteoarthritis
Lead sponsor: TRB Chemedica
Sponsor class: INDUSTRY
First posted: 2017-06-29
Enrollment: 290
Sex: ALL
Minimum age (years): 40
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change in WOMAC A
timeFrame: Day 0 to Day 180
Secondary outcomes:
measure: Lequesne algofunctional index
timeFrame: Day 0 to Day 180
measure: WOMAC B
timeFrame: Day 0 to Day 180
measure: WOMAC C
timeFrame: Day 0 to Day 180
measure: Patient's overall status score in relation to his/her knee osteoarthritis
timeFrame: Day 0 to Day 180
measure: Assessment of overall treatment efficacy by the patient
timeFrame: Day 30 to Day 180
measure: Assessment of overall treatment efficacy by the investigator
timeFrame: Day 30 to Day 180
Other outcomes:
measure: Incidence of all adverse events
timeFrame: Day 0 to Day 180
measure: Incidence of local adverse reactions
timeFrame: Day 30
measure: Assessment of local treatment tolerability by the patient
timeFrame: Day 30
measure: Assessment of local treatment tolerability by the investigator
timeFrame: Day 30
measure: Assessment of overall treatment tolerability by the investigator
timeFrame: Day 30 to Day 180
measure: Assessment of overall treatment tolerability by the patient
timeFrame: Day 30 to Day 180
Locations:
Study officials:
affiliation: APHP Bichat-Claude Bernard, Paris, France
name: Renée Liliane Dreiser, Dr
role: STUDY_CHAIR
affiliation: APHP Henri Mondor, Creteil, France
name: Bernard Avouac, Dr
role: STUDY_CHAIR
affiliation: APHP Lariboisière, Paris, France
name: Thomas Bardin, Prof.
role: PRINCIPAL_INVESTIGATOR
References: