search
Back to results

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

Primary Purpose

Osteoarthritis, Knee

Status
Completed
Phase
Phase 4
Locations
International
Study Type
Interventional
Intervention
Sinovial® (syringe containing sodium hyaluronate solution)
Synvisc® ( syringe containing Hylan G-F 20 solution)
Sponsored by
IBSA Institut Biochimique SA
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Osteoarthritis, Knee

Eligibility Criteria

40 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Interni hemato-onkologická klinika, Fakultní nemocnice
  • ARTHROMED s.r.o.
  • Institute of Rheumatology
  • Centrum léčby pohybového aparátu spol. s.r.o.
  • University Hospital Centre Bois-Guillaume
  • University Hospital Centre of Limoges - Rheumatology Service
  • Orthopädische Universitätsklinik und Poliklinik der RWTH Aachen
  • Nova clinic
  • Orthopädische Praxis
  • Sezione Dipartimentale a valenza provinciale di Reumatologia - AzUSL 8
  • Ospedale Privato Accreditato Nigrisoli
  • Medicina e Traumatologia dello Sport - AzUSL 2 Lucca
  • Unità Operativa di Reumatologia - Istituto Ortopedico Gaetano Pini
  • Rheumatology Unit Santa Chiara Hospital
  • Unità Operativa di Reumatologia - Az. Ospedaliera Universitaria Senese - Policlinico "Le Scotte"
  • F.D. Roosevelt's University Hospital
  • Romjan s.r.o.
  • National Institute of Rheumatic Diseases
  • Rheumatology Clinic, Reumaglobal s.r.o
  • Department of Rheumatology and Institute of Physical Medicine - Zurich University

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Sinovial

Sinvisc

Arm Description

3 intra-articular injections of Sinovial®

Outcomes

Primary Outcome Measures

Improvement in WOMAC pain subscore from baseline

Secondary Outcome Measures

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%

Full Information

First Posted
November 9, 2007
Last Updated
December 3, 2012
Sponsor
IBSA Institut Biochimique SA
search

1. Study Identification

Unique Protocol Identification Number
NCT00556608
Brief Title
Efficacy Study of Intra-articular Hyaluronic Acid in the Knee Osteoarthritis
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
Study Type
Interventional

2. Study Status

Record Verification Date
November 2012
Overall Recruitment Status
Completed
Study Start Date
November 2007 (undefined)
Primary Completion Date
July 2009 (Actual)
Study Completion Date
May 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
IBSA Institut Biochimique SA

4. Oversight

Data Monitoring Committee
No

5. Study Description

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®.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Osteoarthritis, Knee

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
381 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Sinovial
Arm Type
Experimental
Arm Description
3 intra-articular injections of Sinovial®
Arm Title
Sinvisc
Arm Type
Active Comparator
Intervention Type
Device
Intervention Name(s)
Sinovial® (syringe containing sodium hyaluronate solution)
Other Intervention Name(s)
Sinovial®: Class III medical device(CE mark n° 0499)
Intervention Description
2 mL 0.8% sodium hyaluronate (16 mg) solution. 3 intra-articular injections once-a-week.
Intervention Type
Device
Intervention Name(s)
Synvisc® ( syringe containing Hylan G-F 20 solution)
Other Intervention Name(s)
Synvisc®: class III medical device (CE mark n° 0088)
Intervention Description
2 mL 0.8% Hylan G-F 20 (16 mg) solution. 3 intra-articular injections once-a-week.
Primary Outcome Measure Information:
Title
Improvement in WOMAC pain subscore from baseline
Time Frame
to week 26
Secondary Outcome Measure Information:
Title
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%
Time Frame
26 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
40 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Karel PAVELKA, MD
Organizational Affiliation
Institute of Rheumatology-Na Slupi 4 - 12850 Praha 2 (Czech Republic)
Official's Role
Principal Investigator
Facility Information:
Facility Name
Interni hemato-onkologická klinika, Fakultní nemocnice
City
Brno - Bohunice
ZIP/Postal Code
63900
Country
Czech Republic
Facility Name
ARTHROMED s.r.o.
City
Pardubice
ZIP/Postal Code
53002
Country
Czech Republic
Facility Name
Institute of Rheumatology
City
Praha
ZIP/Postal Code
12850
Country
Czech Republic
Facility Name
Centrum léčby pohybového aparátu spol. s.r.o.
City
Praha
ZIP/Postal Code
19061
Country
Czech Republic
Facility Name
University Hospital Centre Bois-Guillaume
City
Bois Guillaume
ZIP/Postal Code
76230
Country
France
Facility Name
University Hospital Centre of Limoges - Rheumatology Service
City
Limoges Cedex
ZIP/Postal Code
87042
Country
France
Facility Name
Orthopädische Universitätsklinik und Poliklinik der RWTH Aachen
City
Aachen
ZIP/Postal Code
52074
Country
Germany
Facility Name
Nova clinic
City
Biberach an der Riss
ZIP/Postal Code
88400
Country
Germany
Facility Name
Orthopädische Praxis
City
Stockach
ZIP/Postal Code
78333
Country
Germany
Facility Name
Sezione Dipartimentale a valenza provinciale di Reumatologia - AzUSL 8
City
Arezzo
ZIP/Postal Code
52100
Country
Italy
Facility Name
Ospedale Privato Accreditato Nigrisoli
City
Bologna
ZIP/Postal Code
40138
Country
Italy
Facility Name
Medicina e Traumatologia dello Sport - AzUSL 2 Lucca
City
Lucca
ZIP/Postal Code
55100
Country
Italy
Facility Name
Unità Operativa di Reumatologia - Istituto Ortopedico Gaetano Pini
City
Milano
ZIP/Postal Code
20122
Country
Italy
Facility Name
Rheumatology Unit Santa Chiara Hospital
City
Pisa
ZIP/Postal Code
56126
Country
Italy
Facility Name
Unità Operativa di Reumatologia - Az. Ospedaliera Universitaria Senese - Policlinico "Le Scotte"
City
Siena
ZIP/Postal Code
53100
Country
Italy
Facility Name
F.D. Roosevelt's University Hospital
City
Banská Bystrica
ZIP/Postal Code
975 17
Country
Slovakia
Facility Name
Romjan s.r.o.
City
Bratislava
ZIP/Postal Code
831 03
Country
Slovakia
Facility Name
National Institute of Rheumatic Diseases
City
Piest'any
ZIP/Postal Code
921 12
Country
Slovakia
Facility Name
Rheumatology Clinic, Reumaglobal s.r.o
City
Trnava
ZIP/Postal Code
917 01
Country
Slovakia
Facility Name
Department of Rheumatology and Institute of Physical Medicine - Zurich University
City
Zürich
ZIP/Postal Code
8091
Country
Switzerland

12. IPD Sharing Statement

Citations:
PubMed Identifier
16307692
Citation
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.
Results Reference
background
PubMed Identifier
15272644
Citation
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.
Results Reference
background
PubMed Identifier
14644851
Citation
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.
Results Reference
background
PubMed Identifier
11014340
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. doi: 10.1002/1529-0131(200009)43:93.0.CO;2-P. No abstract available.
Results Reference
background
PubMed Identifier
12590879
Citation
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.
Results Reference
background
PubMed Identifier
14679274
Citation
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.
Results Reference
background
PubMed Identifier
14996880
Citation
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.
Results Reference
background
PubMed Identifier
16625635
Citation
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.
Results Reference
background
PubMed Identifier
8774185
Citation
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.
Results Reference
background
PubMed Identifier
11048620
Citation
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.
Results Reference
background
PubMed Identifier
14713399
Citation
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.
Results Reference
background
PubMed Identifier
16242361
Citation
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.
Results Reference
background
PubMed Identifier
3068365
Citation
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.
Results Reference
background
PubMed Identifier
12465137
Citation
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.
Results Reference
background
PubMed Identifier
13498604
Citation
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.
Results Reference
background
PubMed Identifier
3741515
Citation
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.
Results Reference
background
PubMed Identifier
17279197
Citation
Lockman LE. Practice tips. Knee joint injections and aspirations: the triangle technique. Can Fam Physician. 2006 Nov;52(11):1403-4. No abstract available.
Results Reference
background
PubMed Identifier
3479839
Citation
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. Erratum In: Scand J Rheumatol 1988;17(3):following 241. Scand J Rheumatol Suppl 1988;73:1.
Results Reference
background
PubMed Identifier
2080414
Citation
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.
Results Reference
background
PubMed Identifier
10625037
Citation
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.
Results Reference
background
PubMed Identifier
9588748
Citation
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.
Results Reference
background
PubMed Identifier
9385702
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. No abstract available.
Results Reference
background
PubMed Identifier
10852302
Citation
Allen E, Krohn K. Adverse reaction to Hylan GF-20. J Rheumatol. 2000 Jun;27(6):1572. No abstract available.
Results Reference
background
PubMed Identifier
12107313
Citation
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.
Results Reference
background
PubMed Identifier
11827424
Citation
Zardawi IM, Chan I. Synvisc perisynovitis. Pathology. 2001 Nov;33(4):519-20. doi: 10.1080/00313020120083296.
Results Reference
background
PubMed Identifier
12701040
Citation
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.
Results Reference
background
PubMed Identifier
11093446
Citation
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.
Results Reference
background
PubMed Identifier
11824949
Citation
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.
Results Reference
background
PubMed Identifier
15608297
Citation
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.
Results Reference
background
PubMed Identifier
15208174
Citation
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.
Results Reference
background
PubMed Identifier
21875678
Citation
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.
Results Reference
derived

Learn more about this trial

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

We'll reach out to this number within 24 hrs