A randomized saline-controlled trial of NASHA hyaluronic acid for knee osteoarthritis

Abstract

Objective:

NASHA hyaluronic acid is administered as a single intra-articular injection to treat the symptoms of osteoarthritis (OA). In a previous trial, post-hoc analysis indicated that NASHA provides significantly greater pain relief than saline in patients with OA confined to the study knee. We aimed to evaluate the safety and efficacy of NASHA in patients with unilateral knee OA.

Research design and methods:

This was a randomized, double-blind, saline-controlled trial. All patients had knee OA confirmed by American College of Rheumatology criteria and a WOMAC pain score of 7–17 in the study knee, but no pain in the previous 3 months in the non-study knee. Treatment comprised a single intra-articular injection of NASHA or saline control. The follow-up period was 6 weeks.

Clinical trial registration:

ClinicalTrials.gov identifier: NCT01806207.

Main outcome measures:

The primary efficacy endpoint was the responder rate, defined as the percentage of patients with ≥40% improvement from baseline in WOMAC pain score and an absolute improvement of ≥5 points.

Results:

A total of 218 patients received study treatment (NASHA: 108, saline: 110). In the main intention-to-treat (ITT) analysis, no statistically significant difference in responder rate was found between the two groups at 6 weeks (NASHA: 30.6%; saline: 26.4%). A post-hoc subgroup analysis of patients without clinical effusion in the study knee at baseline showed a significantly higher 6 week responder rate with NASHA than with saline: 40.6% versus 19.7% (p = 0.0084). A total of 68 adverse events were reported among 44 patients in the NASHA group, compared with 69 adverse events among 44 patients in the saline group. The main weakness of the study was the short, 6 week follow-up duration. In addition, image guidance was not used to ensure injection as intended into the intra-articular space.

Conclusions:

Single-injection NASHA was well tolerated and, although there was no significant benefit versus saline control in the primary analysis, post-hoc analysis showed a statistically significant improvement in pain relief at 6 weeks among patients without clinical effusion at baseline.

Keywords::

• Knee
• NASHA hyaluronic acid gel
• Osteoarthritis
• Saline control

Transparency

Declaration of funding

This clinical trial was supported by Q-Med AB, Uppsala, Sweden (study design, data collection, data analysis). Early versions of the manuscript were supported by Q-Med AB and Smith & Nephew UK Ltd through a Medical Writer (Ken Sutor whilst at Fishawack Communications, 100–102 King Street, Knutsford, UK, WA16 6HQ).

Declaration of financial/other relationships

N.K.A. is a paid consultant for Q-Med AB and Smith & Nephew Inc.; C.Å. has disclosed that he has no significant relationships with or financial interests in any commercial companies related to this study or article; R.D.A. is a Ferring consultant, speaker, Abbott consultant, Novartis consultant, Astra Zeneca speaker, Rotta consultant, Johnson & Johnson consultant, Novozyme consultant, Covidien consultant and Lilly consultant; at the time of the study M.A. was a full time employee of Q-Med AB and M.G.T. was a full-time employee of Smith & Nephew UK Ltd.

CMRO peer reviewers may have received honoraria for their review work. The peer reviewers on this manuscript have disclosed that they have no relevant financial relationships.

Acknowledgements

The Durolane Study 2 group recruited patients in Sweden: Jan Ericsäter, Malmö; Torsten Adalberth, Malmö; Johan Isacson, Stockholm; Christian Åkermark, Stockholm; Anders Björkman, Uppsala; Per-Erik Melberg, Göteborg; UK: Nigel Arden, Southampton; John Dickson, Middlesbrough; Terry Daymond, Sunderland; James Richardson, Oswestry; David Scott, London; and Germany: Jürgen Krämer, Bochum; Tobias Schlegel, Mülheim/Ruhr (Nigel Arden was the coordinating investigator). Thanks to Ulf Olsson (Q-Med, AB) who provided critical insight during the writing of this manuscript.

Notes

*Durolane is a registered trade name of Q-Med AB, Uppsala, Sweden.