title: Safety and performance of Hydros and Hydros-TA for knee osteoarthritis: a prospective, multicenter, randomized, double-blind feasibility trial.
abstract: BACKGROUND
  Studies have evaluated the concomitant use of hyaluronan (HA) with steroids, anti-inflammatory drugs and analgesic agents in an attempt to magnify the extent and duration of pain relief due to knee osteoarthritis. To date there has not been an intra-articular combination therapy available for relief of knee osteoarthritis symptoms--one that combines the fast acting onset of symptom relief provided by a corticosteroid with the long-lasting symptom relief provided by HA in a single injection. The objective of this study was to evaluate the safety and preliminary performance of two new HA formulations, Hydros (hyaluronan-based hydrogel suspended in hyaluronan solution) and Hydros-TA (HA plus 10 mg of triamcinolone acetonide [TA]) in subjects with knee osteoarthritis.
  
  
  METHODS
  We conducted a Phase 2 prospective, multicenter, randomized, double-blind feasibility trial. Participants (n = 98; mean age 60 years) with knee osteoarthritis (Kellgren-Lawrence grade 2 or 3) were randomized to three treatment groups: Hydros, Hydros-TA, and Synvisc-One® (hylan G-F 20). Participants received one 6 ml intra-articular injection in the treatment knee and were evaluated at 2, 6, 13, and 26 weeks post-treatment. Safety was assessed from adverse events at all study visits. The primary efficacy outcome was the change from baseline on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) A (Pain) score for the treatment knee.
  
  
  RESULTS
  Adverse events were similar across treatment groups with the most common being arthralgia, joint swelling, back pain, and joint stiffness. Arthralgia was reported 5 times with Synvisc-One, 4 with Hydros, and 1 with Hydros-TA. Each group demonstrated a reduction in the WOMAC A (Pain) score over 26 weeks: [least-square mean (standard error)] 30.5 (5.1) mm for Hydros; 34.4 (4.7) mm for Hydros-TA; 28.0 (5.4) mm for Synvisc-One and an observed improvement of 2.5 mm (p = 0.64) and 6.4 mm (p = 0.24) over Synvisc-One for Hydros and Hydros-TA, respectively.
  
  
  CONCLUSIONS
  A single injection of Hydros or Hydros-TA was well-tolerated and relieved pain associated with knee osteoarthritis over 26 weeks. Data indicate that Hydros-TA had a more rapid pain relief compared to Hydros alone. A Phase 3 trial is underway to confirm these preliminary results.
  
  
  BACKGROUND
  NCT01134406.
authors.affiliation: Aging, Rehabilitation & Geriatric Care Research Centre, Lawson Health Research Institute & Departments of Family Medicine, Kinesiology and Cardiology, Western University, London, Canada. petrella@uwo.ca.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Petrella
authors.affiliation: Department of Orthopaedic Surgery, Maastricht University Medical Center, Maastricht, the Netherlands. pj.emans@maastrichtuniversity.nl.
authors.forename: Pieter J
authors.initials: PJ
authors.lastname: Emans
authors.affiliation: Department of Family and Community Medicine, University of Toronto & Sport CARE, Women's College Hospital, Toronto, Canada. jkalleyne@crucible.net.
authors.forename: Julia
authors.initials: J
authors.lastname: Alleyne
authors.affiliation: Care to Move, St. Niklaas, Belgium. frank.dellaert@telenet.be.
authors.forename: Frank
authors.initials: F
authors.lastname: Dellaert
authors.affiliation: Aging, Rehabilitation & Geriatric Care Research Centre, Lawson Health Research Institute & Department of Family Medicine and School of Health Studies, Western University, London, Canada. dawn.gill@uwo.ca.|Department of Epidemiology, University of Washington, Seattle, USA. dawn.gill@uwo.ca.
authors.forename: Dawn P
authors.initials: DP
authors.lastname: Gill
authors.affiliation: Carbylan Therapeutics, Palo Alto, USA. mmaroney@carbylan.com.
authors.forename: Marcee
authors.initials: M
authors.lastname: Maroney
mesh_terms: D000305:Adrenal Cortex Hormones / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018771:Arthralgia / Q000188:drug therapy / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D006820:Hyaluronic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D020100:Hydrogels / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007270:Injections, Intra-Articular; D007719:Knee Joint / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000188:drug therapy* / Q000503:physiopathology; D011446:Prospective Studies; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014222:Triamcinolone Acetonide / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D055675:Viscosupplements / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000305:Adrenal Cortex Hormones; D020100:Hydrogels; D055675:Viscosupplements; C049816:hylan; D006820:Hyaluronic Acid; D014222:Triamcinolone Acetonide