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

Abstract

BackgroundThis 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.MethodsTwo 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.ResultsMean 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.ConclusionsThis 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 registrationClinicalTrials.gov (NCT01510535). This trial was registered on January 6, 2012.

Intra-Articular Hyaluronic Acid in the Symptomatic Treatment of Knee Osteoarthritis: A Meta-Analysis of Single-Injection Products

“…Of these, 57 included data for IA HA mono-injection 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70. At the end, 28 studies were included,43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70 whereas 29 studies were removed for 1 or several of the following reasons:Two studies were in combination with surgery: anterior cruc...…”

“…The comparators within the 20 RCTs were:IA saline solution (ie, placebo) for 6 studies;43, 51, 52 , 60, 61, 62IA autologous preparation for 4 studies:56, 57, 64, 65 platelet rich plasma (PRP), plasma rich in growth factors (PRGF), or mesenchymal stem cells (MSC);IA ozone for 1 study 64 ;IA drug (ie, corticosteroid) for 3 studies47, 49, 53;Another IA HA monoinjection for 3 studies, here analyzed as separate arms,45, 46, 48 or ignored for 2 other experimental, nonapproved products 45 ; andIA HA multi-injection for 4 studies . 54, 55, 59, 70 To maintain the same number of injections per patient in both trial arms, 1 study used sham injections from empty syringes 54 and another used IA saline injections 70 …”

“…IA HA multi-injection for 4 studies . 54, 55, 59, 70 To maintain the same number of injections per patient in both trial arms, 1 study used sham injections from empty syringes 54 and another used IA saline injections 70 …”

Clinical Efficacy of a Single-dose of Platelet Rich Plasma in the Management of Early Knee Osteoarthritis: A Randomized Controlled Study With Mri Assessment and Evaluation of Optimal Dose

“…Four ml of high-molecular-weight hyaluronic acid (HMWHA) with a concentration of 22 mg/ml was used for intra-articular administration in placebo group [16].…”

Injections intra articulaires (IA) d'acide hyaluronique (AH) dans le traitement symptomatique de la gonarthrose : une méta-analyse des injections uniques (mono-injections)

“…A partir de là, 57 articles contenaient des données de mono-injection d'AH IA 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70. Au final, 28 essais ont été inclus,43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70 tandis que 29 études ont été retirées pour une ou plusieurs des raisons suivantes:3 essais étaient associés à...…”