Purpose: To determine the effect of intra-articular hyaluronic acid (HA) on gait velocity, pain, and function, in older knee osteoarthritis (OA) patients. Materials and methods: Thirty knee OA patients (Kellgren-Lawrence II-III) [72.44 (± 6.11) years old] were randomized, using the 'RANDBETWEEN' function in Microsoft Excel, to receive three weekly injections of HA (2 ml of 20 mg/ml HA), or placebo (P) (1.2 ml of 0.001 mg/ml HA), with fifteen participants per group. Patients and assessors were blind to treatment. Self-selected and fast gait velocities were measured with the GAITRite system. Knee pain, stiffness, and physical function were measured with the Western Ontario McMaster Osteoarthritis OA index (WOMAC OA index). Data from 1 week, 3 and 6 months post-treatment were analyzed using repeated measures ANOVA. Results: The HA group significantly improved self-selected and fast gait velocity, while the P group only significantly improved self-selected gait velocity. Mean improvements in self-selected gait velocity [Mean (SD); 95% CI] [1.25 (52.4)cm/s; -18.38; 20.88] and fast gait velocity [7.16 (71.75)cm/s; -19.72; 34.04] were not significantly different between groups. Improvements in WOMAC pain scores were significantly greater in the HA group than the P group [-2.47 (6.39); -4.86; -0.08], while improvements in stiffness [-0.87 (2.42); -1.77; 0.04] and physical function [-7.23 (19.77); -14.63; 0.16] scores were not. Conclusions: The overall effect of HA on gait velocity in older knee OA patients was not significant compared to placebo. The preliminary results of improved fast gait velocity following HA treatment should be investigated further, along with the incidence of falls, in a larger sample of older knee OA patients.ClinicalTrials.gov ID: NCT00778076.
<b>OBJECTIVE: </b>To compare the safety and efficacy of a single intra-articular (IA) injection of a new cross-linked hyaluronic acid product, Gel-200, with phosphate buffered saline (PBS, control) in a multi-center randomized controlled trial in patients with symptomatic osteoarthritis (OA) of the knee.<b>DESIGN: </b>Patients were randomized 2:1 to receive a single injection of Gel-200 or PBS, after joint aspiration. The primary measure of effectiveness was Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscores by 100-mm Visual Analog Scale (VAS); secondary outcomes included: total WOMAC, physical function, and stiffness subscores; patient and physician global assessments of disease activity, Outcome Measures in Rheumatology Clinical Trials and Osteoarthritis Research Society International (OMERACT-OARSI) strict responders, as well as safety of Gel-200.<b>RESULTS: </b>Of 379 patients randomized, safety was evaluated in 377 and efficacy in 375 (98.9% randomized) in the intent-to-treat population. Effectiveness of Gel-200 by WOMAC pain subscores was statistically significant at week 13 (P=0.037). Mean improvements from baseline in WOMAC pain subscores consistently favored Gel-200 at each visit. Effectiveness of Gel-200 treatment was statistically significant over weeks 3-13 by WOMAC total score, physical function, and physician global evaluations (P<0.05). The number of "strict" OMERACT-OARSI responders was statistically significant from weeks 6 to 13 (P=0.022). Adverse events were not significantly different between treatment groups, including serious adverse events considered related to study treatment.<b>CONCLUSIONS: </b>This trial demonstrated that a single injection of Gel-200 was well tolerated and relieved pain associated with symptomatic OA of the knee over 13 weeks.<b>Trial Registration Number: </b>ClinicalTrials.gov NTC 00449696.
<b>BACKGROUND: </b>The efficacy and tolerability of 500-730 kDa sodium hyaluronate (Hyalgan®) for treatment of osteoarthritis (OA) pain has been established in clinical trials, but few data are available in the Asian population. We conducted a randomized, double-blind, multicenter, placebo-controlled study to evaluate the efficacy and tolerability of this preparation in a Taiwanese population.<b>METHODS: </b>Two hundred patients with mild to moderate OA of the knee were randomized to receive five weekly intra-articular injections of sodium hyaluronate or placebo. The primary efficacy outcome was the change from baseline to Week 25 in patients' evaluation of pain using a 100-mm visual analog scale (VAS) during the 50-foot walking test. Additional outcomes included Western Ontario and McMaster Universities (WOMAC) scores, time on the 50-foot walking test, patient's and investigator's subjective assessment of effectiveness, acetaminophen consumption, and the amounts of synovial fluid.<b>RESULTS: </b>The Hyalgan® treatment group showed a significantly greater improvement from baseline to Week 25 in VAS pain on the 50-foot walking test than the placebo group (p = 0.0020). The Hyalgan® group revealed significant improvements from baseline to week 25 in WOMAC pain and function score than the placebo group (p = 0.005 and 0.0038, respectively) Other outcomes, such as time on the 50-foot walking test and subjective assessment of effectiveness, did not show any significant difference between groups. Both groups were safe and well tolerated.<b>CONCLUSIONS: </b>The present study suggests that five weekly intra-articular injections of sodium hyaluronate are well tolerated, can provide sustained relief of pain, and can improve function in Asian patients with osteoarthritis of the knee.<b>Trial Registration: </b>Therapeutic study, Level I-1a (randomized controlled trial with a significant difference).
AIM: The aim of this study was to investigate the effect of intra-articular hyaluronic acid (HA) injection on pain and function in knee osteoarthritis (OA).
METHODS: Fourty-eight patients with knee OA were included in this study. The patients were randomized into two groups: one group received HA injections (average molecular weight [MW] 1.5 million Da), and the other group received placebo containing 0.9% saline. Three injections of HA or placebo were given at weeks 1, 2 and 3. The evaluation instruments were: Visual Analog Scale (VAS); Likert Scale; Lequesne <ndex; the Western Ontario and McMaster Universities (WOMAC) Index for Osteoarthritis pain, stiffness, and function, and WOMAC pain subgroups (pain on walking, climbing stairs, at night, on sitting and lying down, on standing); the number of analgesics taken; changes in knee flexion angle; and patient satisfaction. Assessment was performed at weeks 1, 3, 5, and 14 after the first injection.
RESULTS: Significant improvement for almost all parameters was noted in both groups (P <0.05). There was no statistically significant difference between change in outcome after HA or placebo treatment (P >0.05), except for WOMAC pain subscore on walking at final assessment (week 14) which showed greater improvement in the HA-treated group (35.2% versus 9.1%; P=0.01).
CONCLUSION: HA treatment was effective in the management of knee OA and improved knee pain and functional outcome, but there was no statistically significant difference in functional and symptom improvement with respect to saline (placebo) injection.
Objective: To examine the long-term efficacy and safety of five intra-articular injections with hyaluronan in knee osteoarthritis. Methods: A multicentre, randomised, placebo-controlled double-blind study of 337 patients fulfilling the American College of Rheumatology (ACR) criteria for knee osteoarthritis (clinical and laboratory) and with a Lequesne algofunctional index score (LFI) of 10 or greater. Patients received a hyaluronan product (sodium hyaluronate; Hyalgan) (n=167) or saline (n=170) intra-articularly weekly for 5 weeks and were followed up to 1 year. Time to recurrence was the primary efficacy parameter. LFI, pain on walking 50 m based on visual analogue scale (VAS pain 50 m), paracetamol consumption, patients' global assessment, Nottingham health profile, joint effusion and number of responders were secondary efficacy parameters. The efficacy parameters were analysed by intention to treat (ITT) and per protocol (PP). All adverse events (AE) were recorded as safety parameters. Results: Time to recurrence showed no significant treatment effect (ITT analysis, p=0.26). Change from baseline in Lfiand VAS pain 50 m for the ITT population showed no treatment effect. Paracetamol consumption, patients' global assessment, responder rates and AE displayed no significant difference between treatment groups, analysed by both ITT and PP. Treatment compliance was 95% in the hyaluronan group and 99% in the placebo group. No safety problems were registered. Conclusion: In patients fulfilling the ACR criteria for osteoarthritis of the knee with moderate to severe disease activity (Lfi≥10), five intra-articular injections of hyaluronan did not improve pain, function, paracetamol consumption or other efficacy parameters 3, 6, 9 and 12 months after the treatment.
OBJECTIVE: The aim of this study was to investigate the short-term effects of intra-articular injection of hyaluronan (Hylan G-F 20) on proprioception, isokinetic muscle force, self reported pain, and functional condition in patients with knee osteoarthritis (OA). METHODS: 63 patients with stage II-III bilateral knee OA were included in this randomized, placebo controlled, and prospective study. Subjects were randomized with 42 of them into the treatment group and 21 of them into the placebo group. Hyaluronan was intraarticularly injected into both knees of the subjects which were in the treatment group, whereas physiological saline was intraarticularly injected to the subjects which were in the placebo group. Proprioception and the isokinetic muscle force measurement were performed. Visual analogue scale (VAS) and WOMAC scale were used to evaluate pain and physical function. RESULTS: Statistical analysis was performed on 120 knees of 60 patients completing the trial. The average absolute angular error (AAAE) value showing the proprioceptive error level in the treatment group was detected to be statistically significantly lower compared to placebo at the measurements performed after the 3rd injection (p = 0.02) and after one week (p = 0.01). While there was no inter-group difference in isokinetic measurements performed at 180 and 240°/sec, a significant difference was detected at the measurement performed at 60°/sec in favor of the treatment group (p = 0.02). Activity and resting VAS-pain values, WOMAC parameters (except the WOMAC stiffness) were detected to be significantly lower in the treatment group. Local adverse events were not reported in any patient. CONCLUSION: In this study, it was demonstrated that intraarticular injection of hyaluronan in patients with knee OA led to a short-term increase in proprioception and isokinetic muscle force, and also significant improvements in the functional conditions of patients. Long-term studies are needed.
Synovial fluid in patients may differ in molecular weight depending on the presence and degree of osteoarthritis. Treatment is not directed at this relationship. Patients with osteoarthritis of the knee with resting visual analogue scale (VAS) pain of >45 mm were included in a randomized, prospective, double-blind cohort followed for 16 weeks. Patients were randomized at baseline to receive a three intra-articular injection series with one of: dual molecular weight (DMW; 580-780 kDa + 1.2 to 2.0 million Da); low molecular weight (LMW; 500-730 kDa); high molecular weight (HMW; 6 million Da); or saline placebo over 3 weeks. Patients completed baseline assessment of rest and walking VAS pain (primary efficacy variable), collection of a 5-point categorical global satisfaction score, and record of adverse events. Two-hundred and twenty-five patients (age 68 +/- 8 y) were screened and 200 were randomized to one of the four groups. There were no differences at baseline between groups. At 4, 12 and 16 weeks, respectively, walking VAS pain was significantly improved in all treatment groups vs. placebo: DMW (79.6%, p < 0.001; 85.6, p < 0.001; 89.3%, p < 0.001); LMW (73.6%, p < 0.001; 76.4, p < 0.001; 81.3%, p < 0.001) and HMW (69.1%, p < 0.001; 81.0, p < 0.001; 79.1%, p < 0.001). Patients in the DMW group had significantly greater improvement (p < 0.007) in VAS walking pain by 3 weeks (following the second injection) compared to all groups. This difference was persistent at 16 weeks. Greater improvement in patients who received the DMW product was achieved by the second injection persistent at 16 weeks.
OBJECTIVE: Methodological constraints weaken previous evidence on intra-articular viscosupplementation and physiological saline distention for osteoarthritis. We conducted a randomized, patient- and observer-blind trial to evaluate these interventions in patients with painful knee osteoarthritis.
METHODS: We centrally randomized 251 patients with knee osteoarthritis to four weekly intra-articular injections of sodium hyaluronate 2 mL (Hyalgan 10.3 mg/mL) versus physiological saline 20 mL (distention) versus physiological saline 2 mL (placebo) and followed patients for 26 weeks. Inclusion criteria were age over 59 years and daily knee pain more than 20 mm on a 100-mm visual analogue scale (VAS) without satisfactory response to analgesics. During the trial, rescue analgesic were allowed. The primary outcome was pain on movement. The secondary outcomes were pain at rest, pain during the night, Knee Injury and Osteoarthritis Outcome Score (KOOS), Osteoarthritis Research Society International (OARSI) criteria, and global assessment of the patient's condition.
RESULTS: The mean age of the patients was 69.4 years; 55% were women. The effects of hyaluronate 2 mL, physiological saline 20 mL, and physiological saline 2 mL did not differ significantly in reducing knee pain, knee function, or consumption of analgesics. Using OARSI criteria, no significant differences were found. The VAS and KOOS outcomes all improved significantly over time (p<0.0005), regardless of intervention group. No adverse events were reported.
CONCLUSIONS: Intra-articular hyaluronate or distention with physiological saline did not significantly reduce pain compared with physiological saline placebo in patients with osteoarthritis of the knee.
Viscosupplementation consists of injecting exagenous hyaluronan (HA) into the synovial joints to restore the normal rheological environment which deteriorates severely in osteoarthritic (OA) joints. Efficacy might be related to the rheological properties and molecular weight (MW) of the hyaluronan preparations. This prospective, controlled, double-blind, randomised clinical trial was aimed at comparing the elastoviscous properties of a high molecular weight viscosupplement, hylan G-F 20, with that of a lower molecular weight hyaluronan product in order to determine the relationship of elastoviscosity to efficacy, alongside placebo, in the treatment of patients with knee OA. The results were analysed as a "completers" analysis with 59 patients. Primary outcome measures included the Western Ontario and Mc Master Universities' Osteoarthritis Index (WOMAC) for pain, stiffness and function scores, and patient and physician global assessments (0-100 scale). For patient (PGA) and physician global assessments (PhGA), the 0-100 scale was used, with 100 being the worst. Follow-up assessments were made at intervals of 1, 3 and 6 months after the first injection. Local adverse events, such as transient pain at the injection site or warm knee lasting for one night, were recorded in two patients (3%). In all groups, the WOMAC pain score exhibited a significant difference from the baseline value; neither treatment group was significantly different from the placebo group, but total pain score was significantly better than baseline for both of the HA groups at the end of 6 months (p < 0.05). Improvement in WOMAC physical function score favoured both sodium hyaluronate and hylan G-F 20 after the first month, and remained significant until the end of 6 months (p < 0.01). In the placebo group, the physical function scores became worse after the end of the 1st month; the scores at the end of 6 months were no different from those at the beginning. The WOMAC stiffness scores of both of the hyaluronic acid groups improved with the first injection, and remained significantly better than the placebo group until the end of the survey (p < 0.001). All groups expressed improvement with PGA scores after the first injection. At the end of 6 months all three groups were similar, but the treatment groups were significantly better than the placebo group (p < 0.05), and all were significantly better than at the beginning (p < 0.05). The PhGA scores were similar in all groups until after the third injection. The second group was slightly better in the controls at 1 and 3 months, but all the groups were similar at the end of 6 months. Although the placebo group seemed worse, it was not statistically significant. Compared with lower molecular weight HA, the higher molecular weight HA might be more efficacious in treating knee OA, but heterogeneity of previous studies limited definitive conclusions. Patients treated by injection of either of two hyaluronan preparations showed clinical improvement for pain, though no different from the placebo group; WOMAC stiffness scores were better than placebo in the HA groups, whereas PGA scores showed improvement in all groups but HA groups were better than placebo. PhGA scores were worse in the placebo group, but not to a statistically-significant extent. The HA groups did not differ in terms of clinical efficacy.
Purpose: To determine the effect of intra-articular hyaluronic acid (HA) on gait velocity, pain, and function, in older knee osteoarthritis (OA) patients. Materials and methods: Thirty knee OA patients (Kellgren-Lawrence II-III) [72.44 (± 6.11) years old] were randomized, using the 'RANDBETWEEN' function in Microsoft Excel, to receive three weekly injections of HA (2 ml of 20 mg/ml HA), or placebo (P) (1.2 ml of 0.001 mg/ml HA), with fifteen participants per group. Patients and assessors were blind to treatment. Self-selected and fast gait velocities were measured with the GAITRite system. Knee pain, stiffness, and physical function were measured with the Western Ontario McMaster Osteoarthritis OA index (WOMAC OA index). Data from 1 week, 3 and 6 months post-treatment were analyzed using repeated measures ANOVA. Results: The HA group significantly improved self-selected and fast gait velocity, while the P group only significantly improved self-selected gait velocity. Mean improvements in self-selected gait velocity [Mean (SD); 95% CI] [1.25 (52.4)cm/s; -18.38; 20.88] and fast gait velocity [7.16 (71.75)cm/s; -19.72; 34.04] were not significantly different between groups. Improvements in WOMAC pain scores were significantly greater in the HA group than the P group [-2.47 (6.39); -4.86; -0.08], while improvements in stiffness [-0.87 (2.42); -1.77; 0.04] and physical function [-7.23 (19.77); -14.63; 0.16] scores were not. Conclusions: The overall effect of HA on gait velocity in older knee OA patients was not significant compared to placebo. The preliminary results of improved fast gait velocity following HA treatment should be investigated further, along with the incidence of falls, in a larger sample of older knee OA patients.ClinicalTrials.gov ID.: NCT00778076.
