Intra-articular sodium hyaluronate in osteoarthritis of the knee: a multicenter, double-blind study

doi:10.1016/S1063-4584(05)80329-2

Osteoarthritis and Cartilage

Volume 1, Issue 4, October 1993, Pages 233-241

https://doi.org/10.1016/S1063-4584(05)80329-2 Get rights and content

Summary

The efficacy and the safety of intra-articular injections of sodium hyaluronate were studied in patients with osteoarthritis of the knee in a randomized multicenter double-blind study. Two hundred and nine patients received five injections of either 25 mg hyaluronate/2.5 ml (verum, N = 102) or 0.25 mg hyaluronate/2.5 ml (control, N = 107) at weekly intervals. Seven patients in each group were excluded from the protocol-correct efficacy analysis. The Lequesne Index, the first main criterion, showed a significant superiority of the verum-treated patients after the third injection up to the final follow-up examination 9 weeks after the last injection (MANOVA, P < 0.025). The consumption of paracetamol was defined as a complementary main criterion that did not reveal significant differences between the treatment groups. Most of the individual secondary endpoints demonstrated a much better response to the active treatment without reaching the significance level in the intergroup comparisons for the single time-points. Side-effects were confined to local reactions of minor severity and short duration in four patients (six events) of the verum group and in five patients of the control group. Clinical chemistry and hematology remained essentially unchanged.

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Citation Excerpt :
The incidence of serious and non-serious treatment-related AEs has been summarized in Table 2. Overall, 29 of the included trials [12,26–29,31,32,34,35,37–39,41–44,47,48,53–56,58–64] reported on adverse events, none of which found any serious TRAEs following IA injection with saline. Empirical evidence shows that IA saline injections, often used as a “placebo” or “sham” intervention in clinical trials evaluating IA interventions for knee OA, provide a statistically significant effect of saline on both short- (≤3 months) and long-term (6–12 months) pain relief.
Hyaluronic acid and corticosteroids are common intra-articular (IA) therapies widely used for the management of mild to moderate knee osteoarthritis (OA). Many trials evaluating the efficacy of IA administered therapies commonly use IA saline injections as a placebo comparator arm. Using a systematic review and meta-analysis, our objective was to assess the clinical benefit associated with use of IA saline in trials of IA therapies in the treatment of patients with painful knee OA.
MEDLINE and Embase databases were searched for articles published up to and including August 14th, 2014. Two reviewers assessed the eligibility of potential reports and the risk of bias of included trials. We analyzed short (≤3 months) and long-term (6–12 months) pain reduction of the saline arm of included trials using standardized mean differences (SMDs; estimated assuming a null effect in a comparator group) that were combined and weighted using a random effects model. Treatment-related adverse events (AEs) were tabulated and presented using descriptive statistics.
From 40 randomized controlled trials (RCTs) eligible for inclusion only 38 provided sufficient data to be included in the meta-analysis. Based on data with moderate inconsistency IA saline was found to significantly improve short-term knee pain in 32 studies involving 1705 patients (SMD = −0.68; 95% CI: −0.78 to −0.57; P < 0.001; I² = 50%). Long-term knee pain was significantly decreased following IA injection with saline in 19 studies involving 1445 patients (SMD = −0.61; 95% CI: −0.76 to −0.45; P < 0.001) with a substantial degree of inconsistency (I² = 74%). Overall, 29 of the included trials reported on adverse events, none of which found any serious treatment-related AEs following IA injection with saline.
Pain relief observed with IA saline should prompt health care providers to consider the additional effectiveness of current IA treatments that use saline comparators in clinical studies, and challenges of identifying IA saline injection as a “placebo.”
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^*: Supported by Luitpold Pharma Munich.

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Original ArticleIntra-articular sodium hyaluronate in osteoarthritis of the knee: a multicenter, double-blind study*

Summary

Epidemiology with osteoarthritis: Zoetermeer survey. Comparison of radiological osteoarthritis in a Dutch population with that in 10 other populations

Ann Rheum Dis

Obesity and knee osteoarthritis. The Framingham study

Ann Intern Med

Occurrence of symptomatic knee osteoarthritis in rural Finland: a prospective follow up study

Ann Rheum Dis

Clinical trial of intra-articular injection of sodium hyaluronate in patients with osteoarthritis of the knee

Curr Med Res Opin

Intra-articular treatment with sodium-hyaluronate in gonarthrosis: a controlled clinical trial versus placebo

Pharmacotherapeutica

Evaluation of the effect of sodium hyaluronate (SPH) to osteoarthritis of the knee

Ryumachi

Validation of diagnostic criteria and assessment or ‘new medical frontiers’ in the age of the computer

Guidelines for clinical investigation of drugs used in rheumatic diseases

European Drug Guidelines Series

Indexes of severity for osteoarthritis of the hip and knee: Validation-value in comparison with other assessment tests

Scand J Rheumatol

Validation study of WOMAC: a health status instrument for measuring clinically important patient relevant outcomes to antirheumatic drug therapy in patients with osteoarthritis of the hip or knee

J Rheumatol

Concentration and molecular weight of sodium hyaluronate in synovial fluid from patients with rheumatoid arthritis and other arthropathies

Ann Rheum Dis

Modulation of the migration and chemotaxis of PMN cells by hyaluronic acid

Z Rheumatol

Original Article
Intra-articular sodium hyaluronate in osteoarthritis of the knee: a multicenter, double-blind study*