Non-Inferiority of a Single Injection of Sodium Hyaluronate Plus Sorbitol to Hylan G-F20: A 6-Month Randomized Controlled Trial

Abstract

Introduction: Several viscosupplement treatments are available for patients suffering from painful osteoarthritis (OA) of the knee, but few comparative clinical trials have been conducted. The primary objective of the trial was to demonstrate the non-inferiority of Synolis VA (80 mg hyaluronic acid and 160 mg sorbitol) (Group HA1) to Synvisc-One (48 mg hylan GF-20) (Group HA2) at Day 168 in terms of pain relief efficacy in patients with knee OA (Kellgren and Lawrence radiological stage II or III) in whom oral treatment with analgesics, NSAIDs or weak opioids provided insufficient clinical responses or were poorly tolerated.Methods: This was a prospective, multicentre, comparative, randomized, double-blinded trial comparing the two previously indicated viscosupplements, HA1 and HA2. The average VAS pain score (1-100) was 62.5 at baseline (Day 0). The patients were randomized into two parallel groups at Day 0 and followed until Day 168. They received one injection of either HA1 or HA2. The primary end point was the evolution of the Western Ontario and McMaster University (WOMAC) pain index at D168 in the groups. One of the secondary end points was the daily assessment of this index by the patient for 7 days following the injection and thereafter at Day 14. The other secondary end points were the WOMAC pain, stiffness, function and total scores assessed at Day 28, Day 84 and Day 168. At Day 168, efficacy and satisfaction were assessed by the evaluator and by the patient using a Likert scale (7 points). Moreover, the number of strict responders in each group was evaluated according to the The Osteoarthritis Research Society International (OARSI) Standing Committee for Clinical Trials Response Criteria Initiative and the Outcome Measures in Rheumatology (OMERACT) criteria (OMERACT-OARSI). The per protocol (PP) population was used for the primary analysis. Results: A total of 202 patients were randomized. The patients were predominantly female (66%). The median age of the whole population was 65 years, and the median body mass index was 27.4 kg/m 2 . No statistically significant

Assessment of the Response Profile to Hyaluronic Acid Plus Sorbitol Injection in Patients with Knee Osteoarthritis: Post-Hoc Analysis of a 6-Month Randomized Controlled Trial

“…The baseline demographic and clinical characteristics of study participants (PP population) were described in the original publication of the trial [8]. These characteristics are quite similar to those of the ITT population used in the current analysis.…”

“…This study is a post-hoc analysis of data from a 24 week (168 days) prospective, randomized, phase IIIb, double-blind, controlled trial, which was designed to compare two different hyaluronic acid preparations for the symptomatic management of knee OA patients (non-inferiority design). The first compound was a solution containing 80 mg of hyaluronic acid and 160 mg of sorbitol, namely Synolis VA, and the second compound was made of 48 mg hylan GF-20 (Synvisc-One) [8]. Each of these compounds was administered as a single intra-articular injection.…”

“…Recently, a 6-month prospective, multicenter, comparative, randomized, doubleblinded trial was published comparing two HA products (i.e., one made of 80 mg hyaluronic acid and 160 mg sorbitol and the other made of 48 mg hylan GF-20) and their effects on pain and function efficacy in patients with moderate knee OA was published [8]. The objective of the present study is to investigate the responder profile to the HA made of sodium hyaluronate plus sorbitol.…”

Stabilized composition of 26 mg/mL of high molecular weight HA for subcutaneous injection to improve skin quality

“…Sorbitol is described in the FDA Inactive Ingredients Guide, for example, for intra-articular and intra-muscular injections. In combination with hyaluronic acid in injectables, sorbitol has demonstrated its high level of clinical safety and performance for intraocular [8] and intra-articular applications [9][10][11] . No specific side effects related to sorbitol have been reported with these injectable hyaluronic acid compositions, in accordance with the high safety profile of sorbitol [8][9][10][11] .…”

“…In combination with hyaluronic acid in injectables, sorbitol has demonstrated its high level of clinical safety and performance for intraocular [8] and intra-articular applications [9][10][11] . No specific side effects related to sorbitol have been reported with these injectable hyaluronic acid compositions, in accordance with the high safety profile of sorbitol [8][9][10][11] . The intended use of the 2.6% H-HA/3.2% sorbitol composition is the treatment of skin laxity and loss of skin elasticity due to skin aging.…”