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

NCT00556608 | Completed Phase 4

• 1 other identifier: 06CZIFCH/Hai06
• Study Type: interventional
• Target: 381
• Locations: 6 countries
• Sites: 20

Brief 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®.

Conditions

Osteoarthritis, Knee

Outcome Measures

Primary Outcomes (1)

• Improvement in WOMAC pain subscore from baseline

  to week 26

Secondary Outcomes (1)

• 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

Study Arms (2)

Sinovial

EXPERIMENTAL

3 intra-articular injections of Sinovial®

Device: Sinovial® (syringe containing sodium hyaluronate solution)

Sinvisc

ACTIVE COMPARATOR

Device: Synvisc® ( syringe containing Hylan G-F 20 solution)

Interventions

Sinovial® (syringe containing sodium hyaluronate solution) DEVICE

2 mL 0.8% sodium hyaluronate (16 mg) solution. 3 intra-articular injections once-a-week.

Also known as: Sinovial®: Class III medical device(CE mark n° 0499)

Sinovial

Synvisc® ( syringe containing Hylan G-F 20 solution) DEVICE

2 mL 0.8% Hylan G-F 20 (16 mg) solution. 3 intra-articular injections once-a-week.

Also known as: Synvisc®: class III medical device (CE mark n° 0088)

Sinvisc

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• IBSA Institut Biochimique SA: lead

Study Sites (20)

Interni hemato-onkologická klinika, Fakultní nemocnice

Brno-Bohunice, 63900, Czechia

Location

ARTHROMED s.r.o.

Pardubice, 53002, Czechia

Location

Institute of Rheumatology

Prague, 12850, Czechia

Location

Centrum léčby pohybového aparátu spol. s.r.o.

Prague, 19061, Czechia

Location

University Hospital Centre Bois-Guillaume

Bois-Guillaume, 76230, France

Location

University Hospital Centre of Limoges - Rheumatology Service

Limoges, 87042, France

Location

Orthopädische Universitätsklinik und Poliklinik der RWTH Aachen

Aachen, 52074, Germany

Location

Nova clinic

Biberach an der Riss, 88400, Germany

Location

Orthopädische Praxis

Stockach, 78333, Germany

Location

Sezione Dipartimentale a valenza provinciale di Reumatologia - AzUSL 8

Arezzo, 52100, Italy

Location

Ospedale Privato Accreditato Nigrisoli

Bologna, 40138, Italy

Location

Medicina e Traumatologia dello Sport - AzUSL 2 Lucca

Lucca, 55100, Italy

Location

Unità Operativa di Reumatologia - Istituto Ortopedico Gaetano Pini

Milan, 20122, Italy

Location

Rheumatology Unit Santa Chiara Hospital

Pisa, 56126, Italy

Location

Unità Operativa di Reumatologia - Az. Ospedaliera Universitaria Senese - Policlinico "Le Scotte"

Siena, 53100, Italy

Location

F.D. Roosevelt's University Hospital

Banská Bystrica, 975 17, Slovakia

Location

Romjan s.r.o.

Bratislava, 831 03, Slovakia

Location

National Institute of Rheumatic Diseases

Piešťany, 921 12, Slovakia

Location

Rheumatology Clinic, Reumaglobal s.r.o

Trnava, 917 01, Slovakia

Location

Department of Rheumatology and Institute of Physical Medicine - Zurich University

Zurich, 8091, Switzerland

Location

Related Publications (31)

• Theiler R, Bruhlmann 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. doi: 10.1185/030079905X65547.

  PMID: 16307692 BACKGROUND

• Castellacci E, Polieri T. Antalgic effect and clinical tolerability of hyaluronic acid in patients with degenerative diseases of knee cartilage: an outpatient treatment survey. Drugs Exp Clin Res. 2004;30(2):67-73.

  PMID: 15272644 BACKGROUND

• Jordan KM, Arden NK, Doherty M, Bannwarth B, Bijlsma JW, Dieppe P, Gunther K, Hauselmann H, Herrero-Beaumont G, Kaklamanis P, Lohmander S, Leeb B, Lequesne M, Mazieres B, Martin-Mola E, Pavelka K, Pendleton A, Punzi L, Serni U, Swoboda B, Verbruggen G, Zimmerman-Gorska I, Dougados M; Standing Committee for International Clinical Studies Including Therapeutic Trials ESCISIT. EULAR Recommendations 2003: an evidence based approach to the management of knee osteoarthritis: Report of a Task Force of the Standing Committee for International Clinical Studies Including Therapeutic Trials (ESCISIT). Ann Rheum Dis. 2003 Dec;62(12):1145-55. doi: 10.1136/ard.2003.011742.

  PMID: 14644851 BACKGROUND

• 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. doi: 10.1002/1529-0131(200009)43:93.0.CO;2-P. No abstract available.

  PMID: 11014340 BACKGROUND

• Altman RD. Status of hyaluronan supplementation therapy in osteoarthritis. Curr Rheumatol Rep. 2003 Feb;5(1):7-14. doi: 10.1007/s11926-003-0077-6.

  PMID: 12590879 BACKGROUND

• Lo GH, LaValley M, McAlindon T, Felson DT. Intra-articular hyaluronic acid in treatment of knee osteoarthritis: a meta-analysis. JAMA. 2003 Dec 17;290(23):3115-21. doi: 10.1001/jama.290.23.3115.

  PMID: 14679274 BACKGROUND

• Wang CT, Lin J, Chang CJ, Lin YT, Hou SM. Therapeutic effects of hyaluronic acid on osteoarthritis of the knee. A meta-analysis of randomized controlled trials. J Bone Joint Surg Am. 2004 Mar;86(3):538-45. doi: 10.2106/00004623-200403000-00012.

  PMID: 14996880 BACKGROUND

• Bellamy N, Campbell J, Robinson V, Gee T, Bourne R, Wells G. Viscosupplementation for the treatment of osteoarthritis of the knee. Cochrane Database Syst Rev. 2006 Apr 19;2006(2):CD005321. doi: 10.1002/14651858.CD005321.pub2.

  PMID: 16625635 BACKGROUND

• Recommendations for the registration of drugs used in the treatment of osteoarthritis. Group for the respect of ethics and excellence in science (GREES): osteoarthritis section. Ann Rheum Dis. 1996 Aug;55(8):552-7. doi: 10.1136/ard.55.8.552. No abstract available.

  PMID: 8774185 BACKGROUND

• Altman R, Brandt K, Hochberg M, Moskowitz R, Bellamy N, Bloch DA, Buckwalter J, Dougados M, Ehrlich G, Lequesne M, Lohmander S, Murphy WA Jr, Rosario-Jansen T, Schwartz B, Trippel S. Design and conduct of clinical trials in patients with osteoarthritis: recommendations from a task force of the Osteoarthritis Research Society. Results from a workshop. Osteoarthritis Cartilage. 1996 Dec;4(4):217-43. doi: 10.1016/s1063-4584(05)80101-3. No abstract available.

  PMID: 11048620 BACKGROUND

• Strand V, Kelman A. Outcome measures in osteoarthritis: randomized controlled trials. Curr Rheumatol Rep. 2004 Feb;6(1):20-30. doi: 10.1007/s11926-004-0080-6.

  PMID: 14713399 BACKGROUND

• Kirchner M, Marshall D. A double-blind randomized controlled trial comparing alternate forms of high molecular weight hyaluronan for the treatment of osteoarthritis of the knee. Osteoarthritis Cartilage. 2006 Feb;14(2):154-62. doi: 10.1016/j.joca.2005.09.003. Epub 2005 Oct 19.

  PMID: 16242361 BACKGROUND

• Bellamy N, Buchanan WW, Goldsmith CH, Campbell J, Stitt LW. Validation study of WOMAC: a health status instrument for measuring clinically important patient relevant outcomes to antirheumatic drug therapy in patients with osteoarthritis of the hip or knee. J Rheumatol. 1988 Dec;15(12):1833-40.

  PMID: 3068365 BACKGROUND

• Bellamy N. WOMAC: a 20-year experiential review of a patient-centered self-reported health status questionnaire. J Rheumatol. 2002 Dec;29(12):2473-6. No abstract available.

  PMID: 12465137 BACKGROUND

• KELLGREN JH, LAWRENCE JS. Radiological assessment of osteo-arthrosis. Ann Rheum Dis. 1957 Dec;16(4):494-502. doi: 10.1136/ard.16.4.494. No abstract available.

  PMID: 13498604 BACKGROUND

• Altman R, Asch E, Bloch D, Bole G, Borenstein D, Brandt K, Christy W, Cooke TD, Greenwald R, Hochberg M, et al. Development of criteria for the classification and reporting of osteoarthritis. Classification of osteoarthritis of the knee. Diagnostic and Therapeutic Criteria Committee of the American Rheumatism Association. Arthritis Rheum. 1986 Aug;29(8):1039-49. doi: 10.1002/art.1780290816.

  PMID: 3741515 BACKGROUND

• Lockman LE. Practice tips. Knee joint injections and aspirations: the triangle technique. Can Fam Physician. 2006 Nov;52(11):1403-4. No abstract available.

  PMID: 17279197 BACKGROUND

• Lequesne MG, Mery C, Samson M, Gerard P. Indexes of severity for osteoarthritis of the hip and knee. Validation--value in comparison with other assessment tests. Scand J Rheumatol Suppl. 1987;65:85-9. doi: 10.3109/03009748709102182.

  PMID: 3479839 BACKGROUND

• Lequesne M, Samson M, Gerard P, Mery C. [Pain-function indices for the follow-up of osteoarthritis of the hip and the knee]. Rev Rhum Mal Osteoartic. 1990 Oct 30;57(9 ( Pt 2)):32S-36S. French.

  PMID: 2080414 BACKGROUND

• Ali Y, Weinstein M, Jokl P. Acute pseudogout following intra-articular injection of high molecular weight hyaluronic acid. Am J Med. 1999 Dec;107(6):641-2. doi: 10.1016/s0002-9343(99)00255-7. No abstract available.

  PMID: 10625037 BACKGROUND

• Luzar MJ, Altawil B. Pseudogout following intraarticular injection of sodium hyaluronate. Arthritis Rheum. 1998 May;41(5):939-40. doi: 10.1002/1529-0131(199805)41:53.0.CO;2-D. No abstract available.

  PMID: 9588748 BACKGROUND

• 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. No abstract available.

  PMID: 9385702 BACKGROUND

• Allen E, Krohn K. Adverse reaction to Hylan GF-20. J Rheumatol. 2000 Jun;27(6):1572. No abstract available.

  PMID: 10852302 BACKGROUND

• Chen AL, Desai P, Adler EM, Di Cesare PE. Granulomatous inflammation after Hylan G-F 20 viscosupplementation of the knee : a report of six cases. J Bone Joint Surg Am. 2002 Jul;84(7):1142-7.

  PMID: 12107313 BACKGROUND

• Zardawi IM, Chan I. Synvisc perisynovitis. Pathology. 2001 Nov;33(4):519-20. doi: 10.1080/00313020120083296.

  PMID: 11827424 BACKGROUND

• Hamburger MI, Lakhanpal S, Mooar PA, Oster D. Intra-articular hyaluronans: a review of product-specific safety profiles. Semin Arthritis Rheum. 2003 Apr;32(5):296-309. doi: 10.1053/sarh.2002.50008.

  PMID: 12701040 BACKGROUND

• 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.

  PMID: 11093446 BACKGROUND

• Angst F, Aeschlimann A, Michel BA, Stucki G. Minimal clinically important rehabilitation effects in patients with osteoarthritis of the lower extremities. J Rheumatol. 2002 Jan;29(1):131-8.

  PMID: 11824949 BACKGROUND

• Bijlsma JW. Patient centred outcomes in osteoarthritis. Ann Rheum Dis. 2005 Jan;64(1):1-2. doi: 10.1136/ard.2004.025072. No abstract available.

  PMID: 15608297 BACKGROUND

• Tubach F, Ravaud P, Baron G, Falissard B, Logeart I, Bellamy N, Bombardier C, Felson D, Hochberg M, van der Heijde D, Dougados M. Evaluation of clinically relevant changes in patient reported outcomes in knee and hip osteoarthritis: the minimal clinically important improvement. Ann Rheum Dis. 2005 Jan;64(1):29-33. doi: 10.1136/ard.2004.022905. Epub 2004 Jun 18.

  PMID: 15208174 BACKGROUND

• Pavelka K, Uebelhart D. Efficacy evaluation of highly purified intra-articular hyaluronic acid (Sinovial((R))) vs hylan G-F20 (Synvisc((R))) in the treatment of symptomatic knee osteoarthritis. A double-blind, controlled, randomized, parallel-group non-inferiority study. Osteoarthritis Cartilage. 2011 Nov;19(11):1294-300. doi: 10.1016/j.joca.2011.07.016. Epub 2011 Aug 16.

  PMID: 21875678 DERIVED

MeSH Terms

Conditions

Osteoarthritis, Knee

Condition Hierarchy (Ancestors)

Osteoarthritis; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases

Study Officials

• Karel PAVELKA, MD

  Institute of Rheumatology-Na Slupi 4 - 12850 Praha 2 (Czech Republic)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 9, 2007
• First Posted: November 12, 2007
• Study Start: November 1, 2007
• Primary Completion: July 1, 2009
• Study Completion: May 1, 2010
• Last Updated: December 4, 2012

Record last verified: 2012-11

Locations

CH (1); FR (2); CZ (4); IT (6); DE (3); SL (4)