Efficacy Study of Intra-articular Hyaluronic Acid in the Knee Osteoarthritis

Osteoarthritis, Knee Clinical Trial

Official title:

Efficacy Evaluation of Intra-articular Hyaluronic Acid (Sinovial®) vs Synvisc® in the Treatment of Symptomatic Knee Osteoarthritis. A Double-blind, Controlled, Randomised, Parallel-group Non-inferiority Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00556608
• Other study ID #: 06CZIFCH/Hai06
• Status: Completed
• Phase: Phase 4
• First received: November 9, 2007
• Last updated: December 3, 2012
• Start date: November 2007
• Est. completion date: May 2010

Study information

• Verified date: November 2012
• Source: IBSA Institut Biochimique SA
• Contact: n/a
• Is FDA regulated: No
• Health authority: Czech Republic: Ethics CommitteeFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Italy: Ethics CommitteeSwitzerland: Ethikkommission
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to prove the non-inferiority of the intra-articular injection of hyaluronic acid (Sinovial®) in the symptomatic treatment of knee OA in comparison to Synvisc®.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 381
• Est. completion date: May 2010
• Est. primary completion date: July 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 40 Years to 80 Years

Eligibility

Inclusion Criteria:

• Age between 40 and 80 years

• Primary knee OA of the medial or lateral femoro-tibial compartment

• Symptoms for at least 3 months

• Diagnosis according to ACR criteria

• Kellgren & Lawrence radiological grade 2-3

• Patients who failed to respond sufficiently (not responders) to analgesics and/or NSAIDs taken regularly or responders intolerant to the regular use of analgesics and/or NSAIDs.

• Mean WOMAC pain subscore at the target knee >= 40 mm and < 80 mm on a VAS at baseline after wash-out from analgesics/NSAIDs· If bilateral knee OA: definition of the most symptomatic joint at screening based on patient's evaluation and Investigator's clinical judgment and mean WOMAC pain subscore at baseline in the contra-lateral knee < 30 mm

• Written informed consent

• Subject able to understand, co-operative and reliable

Exclusion Criteria:

• BMI >= 32 kg/m2

• Secondary (post-traumatic) knee OA

• Predominantly patello-femoral pain/syndrome

• No remaining joint space width

• Symptomatic hip OA or other interfering health condition

• Severe varus/valgus deformity (>15°)

• History/present evidence of (target knee): inflammatory, infective or metabolic joint diseases; recurrent clinical chondrocalcinosis; crystal arthropaties; osteo-articular pathologies differing from arthrosis; articular fracture; ochronosis; acromegaly; haemochromatosis; Wilson's disease; primary osteochondromatosis; heritable disorders; collagen gene mutations.

• Concomitant rheumatic disease

• Significant injury to the target knee in the last 6 months

• Previous joint replacement/arthroplasty (target knee)

• Arthroscopy/osteotomy/surgery in the past 1 year (target knee)

• Any surgery scheduled in the next 6 months

• Venous or lymphatic stasis in the relevant limb

• Skin infection/disease/trauma at the injection site

• Systemic or i.a. (target knee) corticosteroids in the past 3 months

• I.a. corticosteroids (non-target joint) in the past 4 weeks

• Viscosupplementation (target knee) in the past year

• Recently started (in the last 3 months) physical therapy (target knee)

• Recently (in the last 3 months) started therapy or change in dosage of SYSADOAs

• Ongoing anticoagulant therapy

• Chronic or recurrent use of NSAIDs/analgesics/narcotics because of diseases different from OA of the target knee

• History of allergy or hypersensitivity to hyaluronic acid or paracetamol or avian proteins

• Participation in a clinical study in the last 3 months

• Pregnant or lactating women, and women of childbearing potential not willing to use adequate contraception

• Patients unable to stay in the study for 6 months, non-cooperating, not able to understand

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Osteoarthritis
• Osteoarthritis, Knee

Intervention

Device:
• Sinovial® (syringe containing sodium hyaluronate solution)
2 mL 0.8% sodium hyaluronate (16 mg) solution. 3 intra-articular injections once-a-week.
• Synvisc® ( syringe containing Hylan G-F 20 solution)
2 mL 0.8% Hylan G-F 20 (16 mg) solution. 3 intra-articular injections once-a-week.

Locations

Country	Name	City	State
Czech Republic	Interni hemato-onkologická klinika, Fakultní nemocnice	Brno - Bohunice
Czech Republic	ARTHROMED s.r.o.	Pardubice
Czech Republic	Centrum lécby pohybového aparátu spol. s.r.o.	Praha
Czech Republic	Institute of Rheumatology	Praha
France	University Hospital Centre Bois-Guillaume	Bois Guillaume
France	University Hospital Centre of Limoges - Rheumatology Service	Limoges Cedex
Germany	Orthopädische Universitätsklinik und Poliklinik der RWTH Aachen	Aachen
Germany	Nova clinic	Biberach an der Riss
Germany	Orthopädische Praxis	Stockach
Italy	Sezione Dipartimentale a valenza provinciale di Reumatologia - AzUSL 8	Arezzo
Italy	Ospedale Privato Accreditato Nigrisoli	Bologna
Italy	Medicina e Traumatologia dello Sport - AzUSL 2 Lucca	Lucca
Italy	Unità Operativa di Reumatologia - Istituto Ortopedico Gaetano Pini	Milano
Italy	Rheumatology Unit Santa Chiara Hospital	Pisa
Italy	Unità Operativa di Reumatologia - Az. Ospedaliera Universitaria Senese - Policlinico "Le Scotte"	Siena
Slovakia	F.D. Roosevelt's University Hospital	Banská Bystrica
Slovakia	Romjan s.r.o.	Bratislava
Slovakia	National Institute of Rheumatic Diseases	Piest'any
Slovakia	Rheumatology Clinic, Reumaglobal s.r.o	Trnava
Switzerland	Department of Rheumatology and Institute of Physical Medicine - Zurich University	Zürich

Sponsors (1)

Lead Sponsor	Collaborator
IBSA Institut Biochimique SA

Countries where clinical trial is conducted

Czech Republic,  France,  Germany,  Italy,  Slovakia,  Switzerland, 

References & Publications (30)

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Ehrich EW, Davies GM, Watson DJ, Bolognese JA, Seidenberg BC, Bellamy N. Minimal perceptible clinical improvement with the Western Ontario and McMaster Universities osteoarthritis index questionnaire and global assessments in patients with osteoarthritis. J Rheumatol. 2000 Nov;27(11):2635-41. — View Citation

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Luzar MJ, Altawil B. Pseudogout following intraarticular injection of sodium hyaluronate. Arthritis Rheum. 1998 May;41(5):939-40. — View Citation

Maillefert JF, Hirschhorn P, Pascaud F, Piroth C, Tavernier C. Acute attack of chondrocalcinosis after an intraarticular injection of hyaluronan. Rev Rhum Engl Ed. 1997 Oct;64(10):593-4. — View Citation

Recommendations for the medical management of osteoarthritis of the hip and knee: 2000 update. American College of Rheumatology Subcommittee on Osteoarthritis Guidelines. Arthritis Rheum. 2000 Sep;43(9):1905-15. — View Citation

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Theiler R, Brühlmann P. Overall tolerability and analgesic activity of intra-articular sodium hyaluronate in the treatment of knee osteoarthritis. Curr Med Res Opin. 2005 Nov;21(11):1727-33. — View Citation

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* Note: There are 30 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Improvement in WOMAC pain subscore from baseline		to week 26	No
Secondary	Change in WOMAC OA Index total score and pain, function and stiffness subscores;Change in Lequesne's algofunctional index; Change in global pain (visit assessment); Change in global status by the patient;Change in global status by the Investigator;SPID%		26 weeks	Yes