Comparison of two hyaluronic acid formulations for safety and efficacy (CHASE) study in knee osteoarthritis: a multicenter, randomized, double-blind, 26-week non-inferiority trial comparing Durolane to Artz

Abstract

IntroductionIntra-articular injection of hyaluronic acid (HA) is often used as therapy for knee osteoarthritis because it is less expensive and less aggressive than total knee replacement. Therefore, it is important to document whether HA is safe and efficacious. We tested whether single and multiple injection viscosupplementation with HA is associated with clinically meaningful pain relief in a new randomized clinical trial (RCT). Our objective was to compare safety and efficacy of intra-articular HA in two formulations: one 3.0 ml injection of Durolane versus five 2.5 ml injections of Artz for the treatment of knee osteoarthritis pain.MethodsPatients (N = 349) from the People’s Republic of China were randomized to treatment (Durolane = 175, Artz = 174). The Durolane group received a 3.0 ml injection at week 0 (baseline), with sham skin punctures at weeks 1, 2, 3, and 4. The Artz group received one 2.5 ml injection at each of the same time points. The primary assessment tool was the Likert-type Western Ontario and McMaster University (WOMAC) pain scale at weeks 0, 6, 10, 14, 18, and 26. Secondary assessments were WOMAC physical function, knee stiffness, and global self-assessment, at identical time points. Statistically-controlled analyses were non-inferiority of Durolane over 18, then over 26 weeks, with a priori non-inferiority defined as 8% of the relevant scale. Acetaminophen was permitted as rescue analgesia and all adverse events (AEs) were recorded.ResultsOverall study retention was excellent; 332 patients (95.1%) completed 18 weeks and 319 (91.4%) completed 26 weeks, with no significant retention difference between treatment arms. All variables met non-inferiority criteria over 18 and 26 weeks. Efficacy response in both arms was >90%. Treatment-related AEs were 9.8% (17/174) for Artz and 13.1% (23/175) for Durolane.ConclusionsA single injection of Durolane is non-inferior to 5 injections of Artz over 18 and 26 weeks for pain, physical function, global self-assessment, and knee stiffness. Both treatments were efficacious, safe, and well tolerated.Trial registrationClinicalTrials.gov NCT01295580. Registered 11 February 2011.

Chondroprotective activity of N-acetyl phenylalanine glucosamine derivative on knee joint structure and inflammation in a murine model of osteoarthritis

“…Current therapeutic treatments, including weight reduction, physical exercise, physiotherapy, extra-articular devices, analgesics, opioids, non-steroidal anti-inflammatory drugs, corticoids, glucosamines (GlcNs), diacerein and hyaluronic acid (HA), can only treat symptoms, at best improving functionality and pain 8 . However, given the complexity of the pathology, these therapies are not curative 9 and arthroplasty still remains the only currently available treatment able to provide permanent pain relief and satisfactory function recovery when the final stages of OA are reached 8 .…”

Efficacy of single high-molecular-weight versus triple low-molecular-weight hyaluronic acid intra-articular injection among knee osteoarthritis patients

“…Conversely in our study, there was no difference in e cacy between these two types of HAs. In the study conducted by Zhang et al, [36] the therapeutic effectiveness of single injection of a cross-linked HMW-HA (Durolane) was compared to ve injections of a LMW-HA (Artz), showing that during a period of 26 weeks, Durolane was non-inferior to Artz in terms of pain, physical activity and knee-stiffness. Our study revealed a similar result within a period of same length.…”

“…In a few studies the e cacy of single cross-linked HMW-HA has been investigated, though there exists a discrepancy between them. [33][34][35][36] Our utilized HMW-HA (Arthromac®, Novatex Bioengineering SA Switzerland) is one of these cross-linked products which is indicated for single intra-articular injection in knee OA patients. [37] The aim of current trial was to compare the e cacy and safety of the single cross-linked HMW injection versus triple injection of low-molecular-weight IA-HA among knee OA patients in terms of function and pain improvement during a six-month period.…”

Efficacy of single high-molecular-weight versus triple low-molecular-weight hyaluronic acid intra-articular injection among knee osteoarthritis patients

“…Conversely in our study, there was no difference in efficacy between these two types of HAs. In the study conducted by Zhang et al, 44 the therapeutic effectiveness of single injection of a cross-linked HMW-HA (Durolane) was compared to five injections of a LMW-HA (Artz), showing that during a period of 26 weeks, Durolane was non-inferior to Artz in terms of pain, physical activity and knee-stiffness. 45 Our study revealed a similar result within a period of same length.…”

“…34 In a few studies, the efficacy of single cross-linked HMW-HA has been investigated, though there exists a discrepancy between them. [35][36][37][38] The aim of current trial was to compare the efficacy and safety of the single cross-linked HMW injection versus triple injection of low-molecular-weight IA-HA among knee OA patients in terms of function and pain improvement during a six-month period. Also, we aimed to determine the best IA-HA injection-protocol based on HA characteristics including molecular weight, cross-linkage and number of injections.…”