Efficacy and safety of single injection of cross-linked sodium hyaluronate vs. three injections of high molecular weight sodium hyaluronate for osteoarthritis of the knee: a double-blind, randomized, multi-center, non-inferiority study

BMC Musculoskelet Disord. 2017 May 26;18(1):223. doi: 10.1186/s12891-017-1591-4.

Abstract

Background: This randomized, double-blind, multi-center, non-inferiority trial was conducted to assess the efficacy and safety of a cross-linked hyaluronate (XLHA, single injection form) compared with a linear high molecular hyaluronate (HMWHA, thrice injection form) in patients with symptomatic knee osteoarthritis.

Methods: Two hundred eighty seven patients with osteoarthritis (Kellgren-Lawrence grade I to III) were randomized to each group. Three weekly injections were given in both groups but two times of saline injections preceded XLHA injection to maintain double-blindness. Primary endpoint was the change of weight-bearing pain (WBP) at 12 weeks after the last injection. Secondary endpoints included Western Ontario and McMaster Universities Osteoarthritis index; patient's and investigator's global assessment; pain at rest, at night, or in motion; OMERACT-OARSI responder rate; proportion of patients achieving at least 20 mm or 40% decrease in WBP; and rate of rescue medicine use and its total consumption.

Results: Mean changes of WBP at 12 weeks after the last injection were -33.3 mm with XLHA and -29.2 mm with HMWHA, proving non-inferiority of XLHA to HMWHA as the lower bound of 95% CI (-1.9 mm, 10.1 mm) was well above the predefined margin (-10 mm). There were no significant between-group differences in all secondary endpoints. Injection site pain was the most common adverse event and no remarkable safety issue was identified.

Conclusions: This study demonstrated that a single injection of XLHA was non-inferior to three weekly injections of HMWHA in terms of WBP reduction, and supports XLHA as an effective and safe treatment for knee osteoarthritis.

Trial registration: ClinicalTrials.gov ( NCT01510535 ). This trial was registered on January 6, 2012.

Keywords: Hyaluronic acid; Inflammation; Knee osteoarthritis; Treatment.

Publication types

  • Comparative Study
  • Equivalence Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / administration & dosage*
  • Adjuvants, Immunologic / chemistry
  • Aged
  • Cross-Linking Reagents / administration & dosage*
  • Cross-Linking Reagents / chemistry
  • Double-Blind Method
  • Female
  • Humans
  • Hyaluronic Acid / administration & dosage*
  • Hyaluronic Acid / chemistry
  • Male
  • Middle Aged
  • Osteoarthritis, Knee / diagnosis*
  • Osteoarthritis, Knee / drug therapy*
  • Prospective Studies
  • Treatment Outcome

Substances

  • Adjuvants, Immunologic
  • Cross-Linking Reagents
  • Hyaluronic Acid

Associated data

  • ClinicalTrials.gov/NCT01510535