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Randomized Controlled Trial
. 2019 Dec 10;14(12):e0226007.
doi: 10.1371/journal.pone.0226007. eCollection 2019.

A single intra-articular injection of 2.0% non-chemically modified sodium hyaluronate vs 0.8% hylan G-F 20 in the treatment of symptomatic knee osteoarthritis: A 6-month, multicenter, randomized, controlled non-inferiority trial

Emmanuel Maheu  1 , Bernard Avouac  2 , Renée Liliane Dreiser  3 , Thomas Bardin  4
Affiliations
Randomized Controlled Trial

A single intra-articular injection of 2.0% non-chemically modified sodium hyaluronate vs 0.8% hylan G-F 20 in the treatment of symptomatic knee osteoarthritis: A 6-month, multicenter, randomized, controlled non-inferiority trial

Emmanuel Maheu et al. PLoS One. .

Abstract

Objectives: The aim of the study was to demonstrate the non-inferiority of a single intra-articular injection of 2.0% non-chemically modified sodium hyaluronate (SH) vs 0.8% hylan G-F 20 (control) in symptomatic knee osteoarthritis.

Design: This was a double-blind, randomized, controlled trial conducted in patients with painful tibiofemoral osteoarthritis (American College of Rheumatology criteria) with insufficient response or intolerance to first-line analgesics and regular non-steroidal anti-inflammatory drugs. Subjects received a single intra-articular injection of either SH or hylan G-F 20. The primary outcome was the 6-month change from baseline in the Western Ontario and McMaster Universities Osteoarthritis Index pain subscale (WOMAC A), with a pre-specified lower margin for non-inferiority of 8 mm.

Results: Of the 292 patients randomized (SH: 144), 288 received an injection (SH: 142), 266 completed the study (SH: 134). In the Per Protocol dataset (SH: 113, control: 112), the WOMAC A change at 6 months was -34.3 mm (95% confidence interval (CI): -37.8, -30.8) and -36.2 mm (95% CI: -40.3, -32.1) for the SH and hylan G-F 20 patients, respectively (P = 0.5). The intergroup difference was -1.9 mm (95% CI: -7.3, 3.5). Results were similar in the Full Analysis Set (SH: 139, control: 141) with a difference between the groups of -2.9 mm (95% CI: -7.9, 2.2). A total of 31.3% of the injected patients reported a treatment-emergent adverse event, including injection site reactions (pain, inflammation or effusion) which occurred in 8.5% of the SH patients vs 13.0% of the hylan G-F 20 patients. No serious reactions were reported.

Conclusions: This clinical trial demonstrated the non-inferiority of a single intra-articular injection of SH vs hylan G-F 20 on the WOMAC A change from baseline at 6 months.

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Conflict of interest statement

This clinical trial was sponsored by TRB Chemedica SAS, France (https://ostenil.fr/). I have read the journal's policy and the authors of this manuscript have the following competing interests: EM received personal consulting fees from TRB Chemedica, Bioiberica, Celgène, Expanscience, Genevrier, IBSA, LCA, MEDA-Mylan, Pierre Fabre Labs, and Rottapharm Biotech. BA received personal consulting fees from TRB Chemedica for his membership in the Scientific Board of this clinical trial. He also received personal consultancy fees, travel grants and honoraria for speaking or participating in congresses from Expanscience, Roche, Novartis, Bayer, Sanofi, Vertex, and Pfizer. RLD received personal consulting fees from TRB Chemedica for her membership in the Scientific Board of this clinical trial, as well as travel grants for her participation in a congress. TB received personal consulting fees from TRB Chemedica for his role in the coordination of this clinical trial. This does not alter our adherence to all PLOS ONE policies on sharing data and materials.

Figures

Fig 1
Fig 1. CONSORT flow diagram.
FAS = Full Analysis Set; ITT = Intention-to-Treat; n = number of patients; PP = Per Protocol.
Fig 2
Fig 2. Evolution of the WOMAC pain subscale during the 6-month trial.
The two graphs represent data of the Per Protocol dataset (a) and Full Analysis Set (b). They are presented as means of observed cases ± standard deviation. Sodium hyaluronate group: saltire with dashed line; control group: hollow circle with dotted line; n = number of patients; WOMAC A = Western Ontario and McMaster Universities Osteoarthritis Index pain subscale.
Fig 3
Fig 3. Non-inferiority of sodium hyaluronate vs hylan G-F 20 in the Per Protocol dataset and Full Analysis Set.
Point estimates and 95% confidence interval of the intergroup difference in the primary efficacy endpoint (change from baseline in WOMAC A at 6 months). FAS = Full Analysis Set; PP = Per Protocol dataset; WOMAC A = Western Ontario and McMaster Universities Osteoarthritis Index pain subscale.
Fig 4
Fig 4. Evolution of the secondary efficacy criteria during the 6-month trial (Per Protocol dataset).
The four graphs represent WOMAC stiffness subscale (a), WOMAC function subscale (b), Lequesne index (c) and patient global assessment of disease activity (d). Data are presented as means of observed cases ± standard deviation. Sodium hyaluronate: saltire with dashed line; control group: hollow circle with dotted line; PtGA = patient global assessment of disease activity; WOMAC B, C = Western Ontario and McMaster Universities Osteoarthritis Index stiffness, function subscales.
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Publication types

Grants and funding

This clinical trial was sponsored by TRB Chemedica SAS, France (https://ostenil.fr/). The funding source had no influence on the study design and the collection of data. TRB Chemedica participated in the analysis/interpretation of data, and had a role in the decision to publish and in the preparation of the manuscript.