BACKGROUND: Undenatured type II collagen (UC-II) is a nutritional supplement derived from chicken sternum cartilage. The purpose of this study was to evaluate the efficacy and tolerability of UC-II for knee osteoarthritis (OA) pain and associated symptoms compared to placebo and to glucosamine hydrochloride plus chondroitin sulfate (GC).
METHODS: One hundred ninety one volunteers were randomized into three groups receiving a daily dose of UC-II (40 mg), GC (1500 mg G & 1200 mg C), or placebo for a 180-day period. The primary endpoint was the change in total Western Ontario McMaster Universities Osteoarthritis Index (WOMAC) from baseline through day 180 for the UC-II group versus placebo and GC. Secondary endpoints included the Lequesne Functional Index (LFI), the Visual Analog Scale (VAS) for pain and the WOMAC subscales. Modified intent-to-treat analysis were performed for all endpoints using analysis of covariance and mixed model repeated measures, while incremental area under the curve was calculated by the intent-to-treat method.
RESULTS: At day 180, the UC-II group demonstrated a significant reduction in overall WOMAC score compared to placebo (p = 0.002) and GC (p = 0.04). Supplementation with UC-II also resulted in significant changes for all three WOMAC subscales: pain (p = 0.0003 vs. placebo; p = 0.016 vs. GC); stiffness (p = 0.004 vs. placebo; p = 0.044 vs. GC); physical function (p = 0.007 vs. placebo). Safety outcomes did not differ among the groups.
CONCLUSION: UC-II improved knee joint symptoms in knee OA subjects and was well-tolerated. Additional studies that elucidate the mechanism for this supplement's actions are warranted.
TRIAL REGISTRATION: CTRI/2013/05/003663 ; CTRI/2013/02/003348 .
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.
TRIAL REGISTRATION NUMBER: NCT01425853.
AIM: To compare the efficacy, tolerability and safety of celecoxib, naproxen and placebo in Asian patients with osteoarthritis (OA) of the knee.
METHOD: Patients of Asian descent with knee OA, aged ≥ 45 years, in a flare state with a functional capacity classification of I-III, received celecoxib 200 mg once daily, naproxen 500 mg twice daily or placebo, for 6 weeks. The change in Patient's Assessment of Arthritis Pain (week 6 vs. baseline) was the primary endpoint. Secondary endpoints, including Patient's and Physician's Global Assessments of Arthritis, Western Ontario and McMaster Universities OA Index (WOMAC), use of complementary and alternative medicines, incidence of treatment-emergent adverse events (TEAEs) and measurements of upper gastrointestinal tolerability, were also assessed.
RESULTS: Three hundred and sixty-seven patients were randomized: 145 to celecoxib, 144 to naproxen and 78 to placebo. Celecoxib was as effective as naproxen in reducing OA pain (least squares mean change from baseline in visual analogue scale score [standard error] -37.1 [2.0] for celecoxib and -37.5 [2.0] for naproxen). Patient's and Physician's Global Assessment of Arthritis, WOMAC scores, Pain Satisfaction Scale and Patient Health Questionnaire-9 showed statistically significant improvement in active treatment groups versus placebo, with the exception of naproxen WOMAC scores. Treatment-related TEAEs occurred in 19 (13%), 34 (24%) and six (8%) patients in the celecoxib, naproxen and placebo groups, respectively.
CONCLUSION: Celecoxib and naproxen were comparable in their effects to reduce the signs and symptoms of knee OA in Asian patients. Celecoxib was shown to be safe and well tolerated in this patient population.
OBJECTIVE: To further characterize time-to-first pain relief, effect size, correlations between various outcome measures and durability of relief for single-tablet naproxen 500 mg/esomeprazole 20 mg (NAP/ESO) given twice daily and celecoxib (CEL) (200 mg) given once daily versus placebo in knee osteoarthritis (OA).
METHODS: Unpublished data from two double-blind, double-dummy, placebo-controlled trials in which patients aged ≥ 50 years with knee OA were randomized to NAP/ESO (n = 487), CEL (n = 486) or placebo (n = 246) were pooled (NCT00664560 and NCT00665431). Acute response endpoints: 1) Time to first significant pain response, 2) Western Ontario and McMaster Osteoarthritis Index (WOMAC) pain subscale and 3) American Pain Society Patient Outcome Questionnaire (APS-POQ) scores. Sustainability endpoints: 1) Routine Assessment of Patient Index Data (RAPID3) and 2) WOMAC Stiffness, Pain and Total scores; and Patient Global Assessment (PGA) at 6 and 12 weeks. Effect sizes for all measures were calculated. Rescue pain medication use also was analyzed, as was the correlation of WOMAC to RAPID3.
RESULTS: NAP/ESO produced statistically significant decreases in WOMAC Pain on Days 2-7 and at Weeks 6 and 12 (all p < 0.05); most APS-POQ pain assessments with NAP/ESO were significantly improved on Days 2-7 compared with placebo (all p < 0.05). A good or excellent response occurred in a median of 6 days. RAPID3 and WOMAC total/stiffness/function/PGA scores decreased significantly at Weeks 6 and 12 (all p < 0.05). Placebo-adjusted WOMAC pain effect sizes were 0.44, 0.34 and 0.25 at Day 7, week 6 and week 12, respectively. RAPID3 to WOMAC total and WOMAC pain to RAPID3: Pain scores were highly correlated at 6 and 12 weeks (correlation coefficients >0.80). No significant differences in overall responses were found between CEL and NAP/ESO.
CONCLUSION: Naproxen/esomeprazole produced a significant absolute moderate early pain response, which was maintained for 12 weeks. RAPID3 was found to be highly correlated with the typical OA measure (WOMAC) and might be a useful clinical tool for measuring NSAID response. NCT00664560: https://clinicaltrials.gov/ct2/show/NCT00664560, NCT00665431: https://www.clinicaltrials.gov/ct2/show/NCT00665431.
BACKGROUND: Celecoxib is an effective treatment for osteoarthritis (OA). However, information on its efficacy and safety profile in different racial/ethnic groups is limited. Noticeable differences among racial groups are found in other disease states, but a thorough investigation of OA is lacking. The objective of this study was to determine if celecoxib 200 mg once daily is as effective as naproxen 500 mg twice daily in the treatment of OA of the knee in Hispanic patients.
METHODS: Hispanic patients aged ≥45 years with knee OA were randomized to receive celecoxib 200 mg once daily, naproxen 500 mg twice daily, or placebo for 6 weeks. The primary efficacy variable was the change in Patient's Assessment of Arthritis Pain at 6 weeks compared with baseline. Secondary variables were change in Patient's and Physician's Global Assessments of Arthritis from baseline to week 6/early termination, change in Western Ontario and McMaster Universities OA Index (WOMAC) from baseline to week 6/early termination, change in American Pain Society pain score, Pain Satisfaction Scale, Patient Health Questionnaire (PHQ-9), and measurements of upper gastrointestinal tolerability.
RESULTS: In total, 239 patients completed the trial (96 celecoxib, 96 naproxen, 47 placebo). Celecoxib was as effective as naproxen in reducing OA pain (least squares mean change from baseline [standard error] -39.7 [2.7] for celecoxib and -36.9 [2.6] for naproxen). Patient's and Physician's Global Assessments of Arthritis, WOMAC scores, upper gastrointestinal tolerability, Pain Satisfaction Scale, and PHQ-9 showed no statistically significant differences between the celecoxib and naproxen groups. The incidence of adverse events and treatment-related adverse events were similar among the treatment groups.
CONCLUSION: Celecoxib 200 mg once daily was as effective as naproxen 500 mg twice daily in the treatment of signs and symptoms of knee OA in Hispanic patients. Celecoxib was shown to be safe and well tolerated in this patient population.
OBJETIVO: Determinar la eficacia a corto plazo de los suplementos de glucosamina por vía oral mediante la evaluación de las lesiones estructurales en las articulaciones de la rodilla, tal como se evaluó utilizando 3T imágenes por resonancia magnética (MRI).
MÉTODOS: Este estudio fue diseñado como un estudio doble ciego, aleatorizado, controlado con placebo. La contratación se realiza a través de correos masivos y un registro de la artritis en el suroeste de Pennsylvania. En total, 201 participantes con dolor de leve a moderado en una o ambas rodillas, tal como se definen por un Western Ontario y McMaster Universidades osteoartritis Index (WOMAC) y la puntuación del dolor ≥25 ≤100, se inscribieron. De estos sujetos, el 69,2% tenían un grado de Kellgren / Lawrence ≥2 en al menos 1 de rodilla. Los participantes recibieron 24 semanas de tratamiento con hidrocloruro de glucosamina 1500 mg en forma de bebida o una bebida placebo. El resultado primario se redujo el empeoramiento del daño del cartílago en la RM 3T de ambas rodillas, evaluó de acuerdo con un sistema de puntuación validado, el Todo-RM Organ Score (lombrices). Los resultados secundarios incluyeron el cambio en la lesión de la médula ósea (BML) las puntuaciones en todas las rodillas y el cambio en la excreción urinaria de telopéptido C-terminal de reticulación del colágeno tipo II (CTX-II).
RESULTADOS: La odds ratio (OR) ajustadas para la probabilidad de disminución de daños en el cartílago de más de 24 semanas en cualquier subregión GUSANOS anotadas de la rodilla en el grupo de tratamiento con glucosamina en comparación con el grupo control fue de 0,938 (intervalo de confianza del 95% [IC 95%] 0.528, 1.666). En comparación con los pacientes tratados con glucosamina, los sujetos de control mostraron una mayor mejoría en BMLS (OR ajustada 0,537; IC del 95% 0,291, 0,990) pero no hubo diferencias en el empeoramiento BMLS (OR ajustada IC 0,691, 95% 0.410, 1.166) durante 24 semanas. No había indicios de que el tratamiento con glucosamina disminuye la excreción urinaria de CTX-II (β = -0,10, IC del 95% -0.21, 0.002).
Conclusión: Los resultados de este estudio a corto plazo no proporcionan evidencia de los beneficios estructurales (es decir, las mejoras en las características morfológicas de resonancia magnética o la excreción urinaria de CTX-II) de la administración de suplementos de glucosamina en personas con dolor crónico de rodilla.
OBJETIVO: determinar la eficacia y la seguridad de acetaminofeno de liberación prolongada (ER) 1300 mg dado tres veces al día en comparación con el placebo para el alivio de los signos y síntomas de la cadera o de la osteoartritis de rodilla.
Material y métodos: Sesenta investigadores en 58 sitios privados, ambulatorios, atención primaria en los EE.UU. reclutaron 542 pacientes ambulatorios adultos ≥ 40 años de edad, con moderado a severo dolor de la osteoartritis idiopática en un ensayo aleatorizado, controlado con placebo, doble ciego 12 semanas clínica. Los pacientes fueron asignados aleatoriamente a tratamiento dado tres veces al día de paracetamol 1300 mg (n = 267) o placebo (n = 275).
RESULTADOS: Los tres principales criterios de valoración medidos hasta la semana 12 ER acetaminofeno favorecida de la siguiente manera: mínimos cuadrados (LS) el cambio medio desde la línea de base para la función física WOMAC subescala fue significativamente mayor para ER acetaminofeno que para el placebo (p = 0,011); LS significan evaluación global del paciente de la respuesta al tratamiento fue significativamente mayor para ER acetaminofeno que para el placebo (p = 0,010); LS y el cambio medio desde la línea base para la puntuación de dolor WOMAC subescala fue ligeramente mayor para las ER acetaminofeno que para el placebo (P = 0,054). LS cambio medio desde la línea de base para los objetivos secundarios hasta la semana 12 también favorecida ER paracetamol en comparación con el placebo: de manera significativa para WOMAC puntuación de rigidez subescala (P = 0,004), de manera significativa para la puntuación del índice total de WOMAC (p = 0,013), y marginalmente de Salud de Nottingham energía Perfil subescala (P = 0,057). El porcentaje de pacientes con eventos adversos fue similar en ambos grupos de tratamiento. transaminasas hepáticas superaron 3 x LSN en siete pacientes ER paracetamol y un paciente con placebo. Las elevaciones se atribuyeron a las condiciones de salud en tres de los siete pacientes ER acetaminofeno; elevaciones en los cuatro pacientes restantes volvieron a o hacia normal.
CONCLUSIONES: El acetaminofeno ER 1300 mg, un medicamento de venta libre, dado tres veces al día, pueden proporcionar un alivio eficaz de los signos y síntomas de la artrosis de cadera o de rodilla y fue bien tolerado. ClinicalTrials.gov número de registro: NCT00240799.
OBJETIVO: demostrar la equivalencia clínica entre dos formulaciones estandarizadas Ayurveda (India) (SGCG y SGC), glucosamina y celecoxib (AINE).
MÉTODOS: fórmulas ayurvédicas (extractos de tinospora cordifolia, Zingiber officinale, Emblica officinalis, Boswellia serrata), sulfato de glucosamina (2 g al día) y celecoxib (200 mg al día) fueron evaluados en una, paralelos y eficacia aleatorizado, doble ciego, de cuatro brazo, multicéntrico ensayo de la droga equivalencia de 24 semanas de duración. Un total de 440 pacientes elegibles que sufren de artrosis sintomática de rodilla se inscribieron y monitoreada según el protocolo. Las variables de eficacia primaria fueron dolor activa el cuerpo de soporte de peso (escala analógica visual) y el dolor WOMAC modificado y la puntuación de Likert dificultad funcional (por la rodilla y la cadera); los correspondientes a priori rangos de equivalencia eran ± 1,5 cm, ± 2.5 y ± 8.5.
RESULTADOS: Las diferencias entre los grupos de intervención para la media de los cambios en las variables de eficacia primaria estaban dentro del rango de equivalencia por intención de tratar y análisis por protocolo. Veintiséis pacientes mostraron una mayor transaminasa glutámico pirúvico en suero asintomática (SGPT) con la función del hígado por lo demás normal; siete pacientes (intervención ayurvédica) se retiraron y SGPT normalizaron después de suspender el medicamento. Otros eventos adversos fueron leves y no se diferencian por la intervención. En general, el 28% de los pacientes se retiraron del estudio.
Conclusión: En este estudio controlado de 6 meses de la OA de la rodilla, las formulaciones de Ayurveda (especialmente SGCG) redujo significativamente el dolor de rodilla y la función mejorada de la rodilla y fue equivalente a la glucosamina y celecoxib. El aumento de SGPT inesperada requiere una mayor evaluación de la seguridad.
Prueba de registro: Drogas Registro de Ensayos Clínicos y la India, www.ctri.nic.in, CTRI / 2008/091 / 000.063.
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.
Undenatured type II collagen (UC-II) is a nutritional supplement derived from chicken sternum cartilage. The purpose of this study was to evaluate the efficacy and tolerability of UC-II for knee osteoarthritis (OA) pain and associated symptoms compared to placebo and to glucosamine hydrochloride plus chondroitin sulfate (GC).
METHODS:
One hundred ninety one volunteers were randomized into three groups receiving a daily dose of UC-II (40 mg), GC (1500 mg G & 1200 mg C), or placebo for a 180-day period. The primary endpoint was the change in total Western Ontario McMaster Universities Osteoarthritis Index (WOMAC) from baseline through day 180 for the UC-II group versus placebo and GC. Secondary endpoints included the Lequesne Functional Index (LFI), the Visual Analog Scale (VAS) for pain and the WOMAC subscales. Modified intent-to-treat analysis were performed for all endpoints using analysis of covariance and mixed model repeated measures, while incremental area under the curve was calculated by the intent-to-treat method.
RESULTS:
At day 180, the UC-II group demonstrated a significant reduction in overall WOMAC score compared to placebo (p = 0.002) and GC (p = 0.04). Supplementation with UC-II also resulted in significant changes for all three WOMAC subscales: pain (p = 0.0003 vs. placebo; p = 0.016 vs. GC); stiffness (p = 0.004 vs. placebo; p = 0.044 vs. GC); physical function (p = 0.007 vs. placebo). Safety outcomes did not differ among the groups.
CONCLUSION:
UC-II improved knee joint symptoms in knee OA subjects and was well-tolerated. Additional studies that elucidate the mechanism for this supplement's actions are warranted.
