Objectives To compare the efficacy and safety of chondroitin sulfate plus glucosamine hydrochloride (CS+GH) versus celecoxib in patients with knee osteoarthritis and severe pain. Methods Double-blind Multicentre Osteoarthritis interVEntion trial with SYSADOA (MOVES) conducted in France, Germany, Poland and Spain evaluating treatment with CS+GH versus celecoxib in 606 patients with Kellgren and Lawrence grades 2-3 knee osteoarthritis and moderate-To-severe pain (Western Ontario and McMaster osteoarthritis index (WOMAC) score ≥301; 0-500 scale). Patients were randomised to receive 400 mg CS plus 500 mg GH three times a day or 200 mg celecoxib every day for 6 months. The primary outcome was the mean decrease in WOMAC pain from baseline to 6 months. Secondary outcomes included WOMAC function and stiffness, visual analogue scale for pain, presence of joint swelling/effusion, rescue medication consumption, Outcome Measures in Rheumatology Clinical Trials and Osteoarthritis Research Society International (OMERACT-OARSI) criteria and EuroQoL-5D. Results The adjusted mean change (95% CI) in WOMAC pain was -185.7 (-200.3 to -171.1) (50.1% decrease) with CS+GH and -186.8 (-201.7 to -171.9) (50.2% decrease) with celecoxib, meeting the non-inferiority margin of -40: -1.11 (-22.0 to 19.8; p=0.92). All sensitivity analyses were consistent with that result. At 6 months, 79.7% of patients in the combination group and 79.2% in the celecoxib group fulfilled OMERACT-OARSI criteria. Both groups elicited a reduction >50% in the presence of joint swelling; a similar reduction was seen for effusion. No differences were observed for the other secondary outcomes. Adverse events were low and similarly distributed between groups. Conclusions CS+GH has comparable efficacy to celecoxib in reducing pain, stiffness, functional limitation and joint swelling/effusion after 6 months in patients with painful knee osteoarthritis, with a good safety profile.
Objective. To assess the efficacy and safety of 12-week treatment with ketoprofen in ultradeformable phospholipid vesicles in patients with OA knee pain and to compare the efficacy with that of ketoprofen-free vehicle and celecoxib.Methods. A multicentre, double-blind controlled study in which patients with knee OA and moderate pain were randomized to one of the six arms: topical ketoprofen 50 or 100 mg in ultradeformable vesicles (IDEA-033), 2.2 or 4.4 g ketoprofen-free vehicle (TDT 064), oral celecoxib 100 mg or matching oral placebo, all bd. The primary outcome was change from baseline in the WOMAC pain subscale at week 12.Results. A total of 1395 patients received treatment. Baseline mean WOMAC pain scores ranged from 4.7 to 4.8 across groups. The mean reduction in WOMAC pain score at week 12 was −1.9 (−40.8%) for ketoprofen 50 mg, −1.9 (−40.9%) for ketoprofen 100 mg, −1.9 (−39.8%) for 2.2 g TDT 064, −1.8 (−37.8%) for 4.4 g TDT 064, −1.9 (−40.4%) for celecoxib and −1.4 (−29.3%) for oral placebo. IDEA-033 was not statistically superior to TDT 064. All topical treatments were statistically superior to oral placebo and non-inferior to celecoxib. The most frequent types of treatment-related adverse events reported were gastrointestinal for oral (15.9% for celecoxib) and dermal for topical applications (12.2% for ketoprofen 100 mg).Conclusion. IDEA-033 was not superior to ketoprofen-free vehicle, but both formulations were superior to oral placebo and non-inferior to celecoxib in reducing OA knee pain.Trial registration: ClinicalTrials.gov, http://clinicaltrials.gov/, NCT00716547.
Background. Opioid analgesics are included in treatment guidelines for the symptomatic management of osteoarthritis (OA). Starting with a low dose of opioid and slowly titrating to a higher dose may help avoid intolerable side effects. Methods. Subjects aged ≥40 years, with moderate to severe pain induced by OA of the hip or knee not adequately controlled by previous non-steroidal anti-inflammatory drugs (NSAIDs) or paracetamol treatment, were enrolled. Subjects received OROS hydromorphone 4 mg or placebo once-daily. The dose was titrated every 3-4 days in case of unsatisfactory pain control during the 4-week titration phase. A 12 week maintenance phase followed. The primary efficacy endpoint was the change in "pain on average" measured on the Brief Pain Inventory (BPI) scale from baseline to the end of the maintenance phase. Results. 139 subjects received OROS hydromorphone and 149 subjects received placebo. All efficacy endpoints showed similar improvements from baseline to end of study in the 2 groups. The safety results were consistent with the safety profile of OROS hydromorphone. Conclusion.The study did not meet the primary endpoint; although many subjects' pain was not adequately controlled at inclusion, their pain may have improved with continued paracetamol or NSAID treatment.
This 12-week, multicenter, randomized, double-blind, placebo-controlled, dose-ranging trial evaluated tramadol ER (extended-release tramadol) in the management of osteoarthritis pain. Adults with knee and/or hip osteoarthritis and baseline pain intensity of >=40 on a 100-mm visual analog scale (0 = no pain, 100 = extreme pain) received once-daily tramadol ER 100 mg (n = 201), 200 mg (n = 199), or 300 mg (n = 199), celecoxib 200 mg (n = 202; to test model sensitivity), or placebo (n = 200). Coprimary efficacy variables were Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale, WOMAC physical function subscale, and patient global assessment of disease activity. Tramadol ER 300 mg significantly improved patient global assessment scores compared with placebo (P <= 0.05), but not the other 2 coprimary efficacy variables. Tramadol ER 200 and 100 mg were not significantly different from placebo for the coprimary efficacy variables. Daily diary arthritis pain intensity scores improved significantly for tramadol ER 300 and 200 mg compared with placebo. WOMAC joint stiffness subscale, physician's global assessment, arthritis pain intensity in index and nonindex joints, and overall sleep quality scores improved significantly for tramadol ER 300 mg compared with placebo. Significant differences in efficacy between celecoxib and placebo validated the model sensitivity. Adverse events occurred more frequently with tramadol ER than placebo in the gastrointestinal (nausea, constipation, diarrhea) and central nervous (dizziness, headache) systems. In this study, tramadol ER 300 mg was effective in the management of moderate to severe painful osteoarthritis of the hip or knee. A large, increasing placebo response during the study may have contributed to the lack of statistical separation between tramadol ER 200 or 100 mg and placebo.
<b>OBJECTIVE: </b>In a multicentre study to explore the effects of licofelone as a disease-modifying osteoarthritis drug in comparison with naproxen in patients with knee osteoarthritis (OA), using MRI and x-ray examination. <b>METHODS: </b>Patients with knee OA (n = 355) were randomised to receive either licofelone (200 mg twice a day) or naproxen (500 mg twice a day). MRI and x-ray examinations were performed at baseline, 6 months (MRI only), 12 and 24 months. MRI was used to assess quantitatively changes in cartilage volume, and x-ray examinations (Lyon-Schuss) to measure changes in the mean and minimum joint space width (JSW) in the medial compartment. Questionnaires probing symptoms were completed. Data were presented as intention to treat (ITT) and according to protocol (ATP). <b>RESULTS: </b>Cartilage volume loss in the global joint and medial and lateral compartments was significantly less in the licofelone than in the naproxen group for ITT at 12 and 24 months and for ATP at all times except in the medial compartment. Patients with medial meniscal extrusion had a greater loss of cartilage volume. In these patients, licofelone markedly reduced the cartilage loss for both ITT and ATP at 12 and 24 months. Although licofelone showed less reduction in the JSW than naproxen, this did not reach significance. All clinical variables were improved at 24 months (p<0.001) for both groups, with a good safety profile. <b>CONCLUSION: </b>Licofelone and naproxen were equally effective in reducing OA symptoms; however, licofelone significantly reduced cartilage volume loss over time, thus having a protective effect in patients with knee OA. This study proves the superiority of quantitative MRI over x-ray examinations in a multicentre clinical trial.
This placebo-controlled study examined the analgesic efficacy, safety, and clinical benefit of Tramadol Contramid OAD, a once-daily formulation with both immediate- and extended-release components. Five hundred and fifty-two patients with moderate to severe pain due to osteoarthritis (OA) of the knee were randomized into this multicenter, double-blind, parallel arm study. After randomization to Tramadol Contramid OAD 100, 200, or 300 mg, or to placebo, patients' dose was titrated to the fixed randomized dose and maintained for 12 weeks. Efficacy was evaluated with the Patients' Global Rating of Pain Relief (median ratings at maintenance visits), and the Western Ontario and McMaster University (WOMAC) Pain and Physical Function subscales (percent difference, baseline to end of study) as coprimary endpoints. A responder analysis was conducted (percentage of patients who achieved a 30 percent improvement on their baseline WOMAC pain score). The difference from placebo on the median Patient Global Rating of Pain Relief at the four maintenance visits was statistically significant (200 and 300 mg: p < or = 0.001). Treatment was rated effective or very effective by 75 percent and 80 percent of patients randomized to Tramadol Contramid OAD 200 mg and 300 mg, respectively. There was a 46 percent (300-mg dose; p = 0.016) and 43 percent (200-mg dose; p = 0.05) improvement on the WOMAC pain score (baseline to the end of the study) with Tramadol Contramid OAD compared with 32percent for placebo. The responder analysis demonstrated a statistically significant difference in the percentage of patients who achieved a 30 percent improvement in their baseline WOMAC pain score for both Tramadol Contramid OAD 200 mg (65 percent; p = 0.0095) and 300 mg (65 percent; p = 0.0104) compared with placebo (50 percent). The type and incidence of adverse events were typical of tramadol (nausea, dizziness/vertigo, vomiting, somnolence, and constipation) and the intensity was mild to moderate in 87percent of patients who experienced them regardless of dose. This study shows the efficacy and safety of Tramadol Contramid OAD 200 mg and 300 mg in patients with moderate or severe pain of the knee due to OA.
OBJECTIVE: This study compared the efficacy and tolerability of a once-daily controlled-release formulation of hydromorphone and twice-daily extended-release (ER) oxycodone in patients with chronic, moderate to severe osteoarthritis (OA) pain. METHODS: The study consisted of a 14-day dose-titration and stabilization phase and a 28-day maintenance phase. OROS hydromorphone and ER oxycodone were initiated at dosages of 8 mg QD and 10 mg BID, respectively. Patients maintained diaries in which they rated their pain (from 0 = none to 3 = severe) and pain relief (from 0 = no relief to 4 = complete relief). Noninferiority analyses were conducted on all primary and secondary efficacy variables. RESULTS: One hundred thirty-eight patients (71 OROS hydromorphone, 67 ER oxycodone) received treatment (safety population), and 83 (60.1%) completed the study. There were no statistically significant differences between groups in total WOMAC scores at end point, and similar improvements from baseline in the WOMAC physical function, stiffness, and pain scales were observed in both groups. CONCLUSIONS: Once-daily OROS hydromorphone and twice-daily ER oxycodone provided similar pain relief in these patients with OA of the knee or hip. (PsycInfo Database Record (c) 2021 APA, all rights reserved)
OBJECTIVE: To compare the efficacy of etoricoxib 30 mg with the generally maximum recommended dose of celecoxib, 200 mg, in the treatment of osteoarthritis (OA) in two identically designed studies.
METHODS: Two multi-centre, 26-week, double-blind, placebo-controlled, non-inferiority studies were conducted, enrolling patients who were prior non-steroidal anti-inflammatory drug (NSAID) or acetaminophen users. There were 599 patients in study 1 and 608 patients in study 2 randomized 4:4:1:1 to etoricoxib 30 mg qd, celecoxib 200 mg qd or one of two placebo groups for 12 weeks. After 12 weeks, placebo patients were evenly distributed to etoricoxib or celecoxib based on their initial enrollment randomization schedule. The primary hypothesis was that etoricoxib 30 mg would be at least as effective as celecoxib 200 mg for the time-weighted average change from baseline over 12 weeks for Western Ontario and McMaster (WOMAC) Pain Subscale, WOMAC Physical Function Subscale and Patient Global Assessment of Disease Status. Active treatments were also assessed over the full 26 weeks. Adverse experiences were collected for safety assessment.
RESULTS: In both studies, etoricoxib was non-inferior to celecoxib for all three efficacy outcomes over 12 and 26 weeks; both were superior to placebo (P < 0.001) for all three outcomes in each study over 12 weeks. The safety and tolerability of etoricoxib 30 mg qd and celecoxib 200 mg qd were similar over 12 and 26 weeks.
CONCLUSIONS: Etoricoxib 30 mg qd was at least as effective as celecoxib 200 mg qd and had similar safety in the treatment of knee and hip OA; both were superior to placebo. ClinicalTrials.gov Identifiers: NCT00092768; NCT00092791.
The objective of this study was to evaluate the efficacy, safety and tolerability of lumiracoxib compared with placebo and celecoxib in patients with osteoarthritis (OA). Following a 3- to 7-day washout period for previous non-steroidal anti-inflammatory drugs, 1,600 patients aged >or=18 years with primary knee OA were randomized to receive lumiracoxib 200 or 400 mg once daily (o.d.), celecoxib 200 mg o.d. or placebo for 13 weeks. Primary efficacy variables were OA pain intensity in the target knee, patient's global assessment of disease activity and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale and total scores at week 13. Secondary variables included OA pain intensity in the target knee and physician's and patient's global assessments of disease activity by visit. Exploratory analysis of responder rates using the Outcomes Measures in Rheumatology Clinical Trials-Osteoarthritis Research Society International (OMERACT-OARSI) criteria was performed. Safety and tolerability were assessed. Lumiracoxib was superior to placebo in all primary and secondary variables and was generally similar to celecoxib. There were no statistically significant differences between the two doses of lumiracoxib. All active treatments were significantly more effective than placebo at weeks 2 and 13 in terms of response to treatment assessed using OMERACT-OARSI criteria. The incidence of adverse events was similar across the groups. Lumiracoxib 200 mg o.d. is a well-tolerated and effective treatment option for OA of the knee, providing pain relief and improved functional status with efficacy superior to placebo and similar to celecoxib. Lumiracoxib demonstrated a tolerability profile similar to placebo and celecoxib.
OBJECTIVE: This study evaluated the efficacy and safety of tramadol extended-release (tramadol ER) tablets once daily in subjects with osteoarthritis pain.
METHODS: This 12-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group clinical trial included 1020 adults with osteoarthritis of the knee or hip and baseline pain intensity >or= 40 on a 100-mm pain visual analog scale (0 = no pain, 100 = extreme pain). Subjects took placebo or were titrated to a target dose of tramadol ER 100, 200, 300, or 400 mg once daily.
MAIN OUTCOME MEASURES: The co-primary efficacy variables were pain and physical function subscales of the WOMAC Osteoarthritis Index and subject global assessment of disease activity.
RESULTS: Mean changes in WOMAC Osteoarthritis Index pain and physical function subscales were significantly different between tramadol ER and placebo, overall (p <or= 0.021) and for each dose (p <or= 0.050). However, the protocol-specified decision rule for the 3 co-primary endpoints was not satisfied because the overall comparison of subject global assessment of disease activity was not statistically significant (p = 0.079). All doses of tramadol ER once daily were more effective than placebo (p <or= 0.050) for WOMAC Osteoarthritis Index joint stiffness subscale, WOMAC Osteoarthritis Index composite score, pain intensity of the index joint, and daily pain intensity scores. Tramadol ER 200 and 300 mg were significantly more effective than placebo (p <or= 0.050) for subject global assessment of disease activity and pain intensity of non-index joints. Adverse events (e.g., constipation, dizziness, nausea, somnolence, headache) occurred most often with tramadol ER 400 mg.
CONCLUSIONS: Tramadol ER 100-300 mg once daily was associated with significant improvement in pain intensity and physical function, and was well tolerated, despite the use of a fixed-dose study design not reflective of usual clinical practice. Tramadol ER is a useful treatment option for patients with osteoarthritis pain.
Objectives To compare the efficacy and safety of chondroitin sulfate plus glucosamine hydrochloride (CS+GH) versus celecoxib in patients with knee osteoarthritis and severe pain. Methods Double-blind Multicentre Osteoarthritis interVEntion trial with SYSADOA (MOVES) conducted in France, Germany, Poland and Spain evaluating treatment with CS+GH versus celecoxib in 606 patients with Kellgren and Lawrence grades 2-3 knee osteoarthritis and moderate-To-severe pain (Western Ontario and McMaster osteoarthritis index (WOMAC) score ≥301; 0-500 scale). Patients were randomised to receive 400 mg CS plus 500 mg GH three times a day or 200 mg celecoxib every day for 6 months. The primary outcome was the mean decrease in WOMAC pain from baseline to 6 months. Secondary outcomes included WOMAC function and stiffness, visual analogue scale for pain, presence of joint swelling/effusion, rescue medication consumption, Outcome Measures in Rheumatology Clinical Trials and Osteoarthritis Research Society International (OMERACT-OARSI) criteria and EuroQoL-5D. Results The adjusted mean change (95% CI) in WOMAC pain was -185.7 (-200.3 to -171.1) (50.1% decrease) with CS+GH and -186.8 (-201.7 to -171.9) (50.2% decrease) with celecoxib, meeting the non-inferiority margin of -40: -1.11 (-22.0 to 19.8; p=0.92). All sensitivity analyses were consistent with that result. At 6 months, 79.7% of patients in the combination group and 79.2% in the celecoxib group fulfilled OMERACT-OARSI criteria. Both groups elicited a reduction >50% in the presence of joint swelling; a similar reduction was seen for effusion. No differences were observed for the other secondary outcomes. Adverse events were low and similarly distributed between groups. Conclusions CS+GH has comparable efficacy to celecoxib in reducing pain, stiffness, functional limitation and joint swelling/effusion after 6 months in patients with painful knee osteoarthritis, with a good safety profile.
