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1.
Moxibustion versus diclofenac sodium gel for the treatment of knee osteoarthritis: a study protocol for a double-blinded, double-placebo, randomised controlled trial.
Zhou, JY, Luo, L, Zhu, LL, Yin, HY, Wu, Q, Peng, JX, Zhang, CS, Lv, P, Tang, Y, Yu, SG
BMJ open. 2017;(4):e012879
Abstract
INTRODUCTION Knee osteoarthritis is a common form of arthritis in elderly patients that is characterised by pain and functional limitation. Moxibustion has been employed to relieve chronic pain as an alternative therapy for knee osteoarthritis. However, the evidence of its efficacy is equivocal due to the low methodological quality in most clinical studies. Therefore, we are performing a double-blinded, double-placebo, randomised controlled trial to evaluate the efficacy of moxibustion in participants with knee osteoarthritis. METHODS AND ANALYSIS This is a multicentre, double-blinded, double-placebo, randomised controlled clinical trial. 144 eligible participants with knee osteoarthritis will be randomly assigned to two different groups in a 1:1 ratio. Participants in the moxibustion group will undergo active moxibustion plus placebo gel, whereas participants in the control group will receive diclofenac sodium gel plus placebo moxibustion. Each participant will receive 12 sessions of active/placebo moxibustion at three acupoints (ST35, ST36 and EX-LE4) as well as 2 months of follow-up. Diclofenac sodium gel or placebo gel at a dose of 4 g per knee will be applied three times per day for 4 weeks. The primary outcome measure will be the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score change at the end of the intervention period from baseline. The secondary outcome measures include changes of other subscales (pain, stiffness and function) of WOMAC, visual analogue scale and patient globalassessment. The safety of moxibustion and diclofenac sodium gel will be assessed at every visit. ETHICS AND DISSEMINATION This trial has been approved by the Sichuan Regional Ethics Review Committee (permission number: 2015KL-014). The results of this study are expected to provide clinical evidence on the efficacy of moxibustion for pain relief and physical function improvement in patients with knee osteoarthritis. The findings will be submitted for publication in peer-reviewed medical journals and presented at relevant academic conferences. TRIAL REGISTRATION NUMBER NCT02769572.
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2.
Topical Fluorometholone Versus Diclofenac Sodium in Cases With Perennial Allergic Conjunctivitis.
Li, Z, Chen, W, Zhang, Y, Jhanji, V, Fan, Z, Mu, G
Eye & contact lens. 2015;(5):310-3
Abstract
PURPOSE To compare the efficacy of diclofenac sodium (DS) 0.1% and fluorometholone (FL) 0.1% in patients with perennial allergic conjunctivitis. METHODS Fluorometholone 0.1% or DS 0.1% eye drops were topically administrated 4 times daily for 4 weeks in patients with perennial allergic conjunctivitis. Assessment was conducted with a 4-point rating scale (0=none, 1=mild, 2=moderate, and 3=severe) for 4 signs and 5 symptoms. RESULTS Two hundred sixty-one patients were recruited. The demographics and baseline skin prick scores between both groups were comparable. Mean baseline scores in DS and FL group were 6.77 ± 2.24 and 6.34 ± 2.10, respectively. The scores rapidly decreased to 3.28 ± 1.47 and 2.69 ± 1.44 on day 7. Diclofenac sodium expressed a slower effect compared with FL within the first 3 days of treatment (P=0.01). CONCLUSIONS The efficacy of topical FL and DS was comparable for the management of cases with perennial allergic conjunctivitis. However, FL led to a more rapid alleviation of signs and symptoms as compared with DS in early days after the initiation of treatment.
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3.
Efficacy and safety of low dose subcutaneous diclofenac in the management of acute pain: a randomized double-blind trial.
Dietrich, T, Leeson, R, Gugliotta, B, Petersen, B
Pain practice : the official journal of World Institute of Pain. 2014;(4):315-23
Abstract
OBJECTIVE Diclofenac is an effective and well-tolerated nonsteroidal anti-inflammatory drug (NSAID) frequently used in the treatment of acute pain. Marketed formulations for parenteral administration usually contain 75 mg/3 mL of diclofenac sodium, which provide limited dosing flexibility, and are usually given intramuscularly. METHODS We present a randomized, double-blind, active comparator- and placebo-controlled, parallel-group phase III multicenter study, investigating efficacy and tolerability of a new 1 mL-volume formulation of diclofenac sodium (25, 50 or 75 mg) containing hydroxypropyl-β-cyclodextrin (HPβCD) as a solubility enhancer. This low-volume formulation allows subcutaneous (SC), in addition to intramuscular (IM) administration. Patients developing moderate-to-severe pain (≥ 50 mm on Visual Analogue Scale) after third molar extraction under local anesthesia were randomized to one of the 4 SC injections: 25 mg diclofenac HPβCD (n = 77), 50 mg diclofenac HPβCD (n = 76), 75 mg diclofenac HPβCD (n = 78), or placebo (n = 75). RESULTS Mean pain intensity difference at 1.5 hours postdose (primary endpoint) was higher in all diclofenac-treated groups than placebo group. The adjusted means (95% CI) were 36.5 (31.7 to 41.2) in diclofenac 25 mg group, 37.3 (32.6 to 42.1) in diclofenac 50 mg group, 37.7 (33.0 to 42.4) in diclofenac 75 mg group, and 12.3 (7.44 to 17.1) in placebo group. Both 25 and 50 mg doses of diclofenac produced significantly greater pain relief than placebo (P < 0.001 in both comparisons). CONCLUSION Single SC doses of diclofenac HPβCD of 25 and 50 mg are effective and well tolerated for relieving pain compared with placebo.
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4.
Analgesic efficacy and safety of a novel injectable formulation of diclofenac compared with intravenous ketorolac and placebo after orthopedic surgery: a multicenter, randomized, double-blinded, multiple-dose trial.
Daniels, S, Melson, T, Hamilton, DA, Lang, E, Carr, DB
The Clinical journal of pain. 2013;(8):655-63
Abstract
OBJECTIVES A novel injectable formulation of diclofenac, Dyloject, utilizes hydroxypropyl-β-cyclodextrin (HPβCD) as a solubilizing agent, allowing dosing as a small-volume intravenous bolus for postoperative pain. In this test of the efficacy and safety of HPβCD diclofenac, we hypothesized that HPβCD diclofenac would relieve moderate and severe pain after orthopedic surgery. PATIENTS AND METHODS Adults 18 to 85 years old with moderate and severe pain within 6 hours after surgery were randomized to HPβCD diclofenac, ketorolac tromethamine, or placebo, and stratified by risk cohort. The HPβCD diclofenac non-high-risk cohort dose was 37.5 mg, the high-risk cohort received 18.75 mg, and patients ≥95 kg received 50 mg. The ketorolac dose was 30 mg in the non-high-risk and high-weight cohorts and 15 mg in the high-risk cohort. Rescue intravenous morphine was given for pain as needed. Efficacy was measured by the sum of pain intensity differences (SPID). RESULTS Mean SPID scores of 277 patients were significantly better with HPβCD diclofenac and ketorolac than with placebo (P<0.0001), across all risk cohorts (P<0.05). HPβCD diclofenac was associated with better SPID scores, faster onset of analgesia, and significantly lower opioid requirement (P<0.008) than ketorolac. In patients more than or equal to 65 years, HPβCD diclofenac was associated with significantly better analgesic efficacy (P=0.05), and lower opioid requirement versus ketorolac. The incidence of treatment-related adverse events was similar across groups. DISCUSSION HPβCD diclofenac is safe and efficacious for acute moderate and severe pain after orthopedic surgery and significantly spares morphine use.
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5.
A randomized, double-blind, placebo-controlled multicentre study to evaluate the efficacy and safety of diclofenac 4% spray gel in the treatment of acute uncomplicated ankle sprain.
Predel, HG, Giannetti, B, Seigfried, B, Novellini, R, Menke, G
The Journal of international medical research. 2013;(4):1187-202
Abstract
OBJECTIVE A prospective, randomized, double-blind, placebo-controlled, parallel-group multicentre study to evaluate the efficacy and safety of diclofenac 4% spray gel for the treatment of acute, uncomplicated ankle sprain. METHODS Outpatients with acute, uncomplicated, one-sided ankle sprain were randomly assigned to receive diclofenac 4% spray gel or placebo (vehicle) three times daily for 14 ± 1 days. The main efficacy endpoint was the intra-individual response to treatment (≥ 50% decrease in swelling of the injured ankle after a treatment period of ≤ 10 days). RESULTS The response rate was significantly higher in the diclofenac group (n = 118) than the placebo group (n = 114) (91.5% vs. 82.5%). After 3-4 days' treatment, diclofenac spray significantly reduced swelling, spontaneous pain, pain on active movement and tenderness compared with placebo. Diclofenac spray was well tolerated, with a low overall rate of adverse events. CONCLUSIONS Diclofenac 4% spray gel rapidly relieves pain and improves mobility in patients with acute, uncomplicated ankle sprain and is well tolerated. It may be a useful treatment option for other acute soft tissue injuries.
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6.
Correlation of pain relief with physical function in hand osteoarthritis: randomized controlled trial post hoc analysis.
Barthel, HR, Peniston, JH, Clark, MB, Gold, MS, Altman, RD
Arthritis research & therapy. 2010;(1):R7
Abstract
INTRODUCTION Nonsteroidal anti-inflammatory drugs are recommended for the relief of pain associated with hand osteoarthritis (OA) but do not alter the underlying structural changes that contribute to impaired physical function. The current analysis examined the relationship of pain relief with measures of function and global rating of disease in patients with hand OA. METHODS This was a combined analysis of 2 prospective, randomized, double-blind, 8-week, multicenter, parallel-group studies comparing diclofenac sodium 1% gel with placebo gel (vehicle) in patients with radiographically confirmed mild to moderate hand OA. Patients (n = 783) aged > or = 40 years applied diclofenac sodium 1% gel (2 g) or vehicle to each hand 4 times daily for 8 weeks. Outcome measures included pain intensity assessed on a 100-mm Visual Analog Scale (VAS); the Australian/Canadian Osteoarthritis Hand Index (AUSCAN) subscales for pain, stiffness, and physical function (100-mm VAS); and a global rating of disease (100-mm VAS). Change in VAS pain intensity from baseline to week 8 was categorized (<0%, 0%-<15%, 15%-<30%, 30%-<50%, 50%-<70%, and > or = 70%) without regard to treatment and compared in each category with the mean change from baseline in each AUSCAN subindex and the global rating of disease. Pearson correlations between changes in outcome measures from baseline to week 8 were calculated. RESULTS Changes in VAS pain intensity were accompanied by similar changes in AUSCAN scores and global rating of disease. Pearson correlations confirmed significant associations (P < 0.001) between change in VAS pain intensity and changes in AUSCAN pain (correlation coefficient [r] = 0.81), AUSCAN function (r = 0.75), AUSCAN stiffness (r = 0.66), and global rating of disease (r = 0.76). CONCLUSIONS Pain relief correlated with improvements in physical function, stiffness, and global rating of disease in patients with hand OA, irrespective of treatment. This suggests that pain or anticipation of pain inhibits physical function and influences patient perception of disease severity in hand OA. These results also suggest that any intervention to relieve the pain of hand OA may improve function and patient perception of disease severity, despite the absence of a disease-modifying mechanism of action. TRIAL REGISTRATION Clinicaltrials.gov NCT00171652, NCT00171665.
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7.
Extent and time course of pain intensity upon treatment with a topical diclofenac sodium patch versus placebo in acute traumatic injury based on a validated end point: post hoc analysis of a randomized placebo-controlled trial.
Mueller, EA, Kirch, W, Reiter, S
Expert opinion on pharmacotherapy. 2010;(4):493-8
Abstract
OBJECTIVE To investigate the extent and time course of pain intensity upon treatment with a topical diclofenac patch compared with placebo in acute traumatic sport injury based on a validated and established end point. METHODS Post hoc analysis of a randomized, placebo-controlled, double-blind, multicentre, 1-week study in 120 patients with traumatic blunt soft tissue injury. Visual analogue scale (VAS) scores (in millimetres) for pain on movement were analysed. The mean absolute VAS changes in pain intensity from baseline over the study course were calculated for the diclofenac patch formulation (active) and placebo; mean differences between active and placebo were assessed twice daily during the first 3 days after enrolment and then once daily up to day 7. RESULTS The diclofenac patch was consistently superior to placebo in relieving pain. The mean differences compared with placebo were greatest on day 2 (23.6 - 30.6 mm, p < 0.0001) and day 3 (24.5 - 24.6 mm, p < 0.0001). Diminishing differences were observed over the study course. CONCLUSION The investigated diclofenac sodium patch provides clinically relevant pain relief in patients with acute traumatic injuries. Maximum effects versus placebo are detected at 2 - 3 days post-injury. This analysis may serve as useful information for the planning of clinical trials in acute traumatic injury.
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8.
Misoprostol effects on diclofenac-induced cardiorenal changes in salt-sensitive patients with hypertension: the MEDIC Study.
Munger, MA, Gardner, SF, Ateshkadi, A, Rabetoy, GM, Barri, YM, Stoddard, GJ, Cheung, AK, ,
Pharmacotherapy. 2008;(7):834-42
Abstract
STUDY OBJECTIVE To determine whether coadministration of misoprostol with the nonsteroidal antiinflammatory drug diclofenac lessens the increase in blood pressure and improves the alterations in renal hemodynamics induced by diclofenac. DESIGN Prospective, randomized, double-blind, placebo-controlled, crossover study. SETTING Two university research centers. PATIENTS Nineteen senior (mean age 62 yrs [range 55-73 yrs]), salt-sensitive patients with stage 1 or 2 hypertension. INTERVENTION After a 3-week antihypertensive withdrawal lead-in phase, patients received either diclofenac 75 mg alone or diclofenac 75 mg plus misoprostol 200 microg twice/day for 14 days. After a 10-day washout period, patients received the alternate treatment. MEASUREMENTS AND MAIN RESULTS Blood pressure was measured by 24-hour ambulatory blood pressure monitoring, effective renal plasma flow (ERPF) rate was determined by para-aminohippurate clearance, and glomerular filtration rate (GFR) was measured by iothalamate clearance. Mean arterial pressure (MAP = diastolic blood pressure + 0.33[systolic - diastolic blood pressure]) and rate-pressure product (RPP = systolic blood pressure x heart rate x 10(-2)) were also used to compare treatment groups. Diclofenac alone increased MAP by a mean +/- SEM of 5.0 +/- 1.0 mm Hg and RPP by 337 +/- 181 units compared with baseline. The ERPF rate and GFR decreased by 40.5 +/- 26.9 ml/minute and 14.1 +/- 6.5 ml/minute, respectively. Diclofenac plus misoprostol decreased the diclofenac-induced increase in MAP by 3.3 +/- 1.0 mm Hg (95% confidence interval [CI] 1.1-5.3 mm Hg, p=0.004) and decreased the RPP by 724 +/- 238 units (95% CI 225-1223 units, p=0.007). The ERPF rate increased by 56.1 +/- 35.0 ml/minute (95% CI -24.7-137.0 ml/min, p=0.15) and GFR by 18.1 +/- 7.1 ml/minute (95% CI 1.9-34.5 ml/min, p=0.03). Diclofenac alone was relatively well tolerated; no adverse effects were reported with diclofenac plus misoprostol. CONCLUSION In senior salt-sensitive patients with hypertension, coadministration of misoprostol with diclofenac attenuated the blood pressure elevation and renal vasoconstrictive effects of diclofenac and was well tolerated.
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9.
Effect of adjunctive diclofenac with verteporfin therapy to treat choroidal neovascularization due to age-related macular degeneration: phase II study.
, , Boyer, DS, Beer, PM, Joffe, L, Koester, JM, Marx, JL, Weisberger, A, Yoser, SL
Retina (Philadelphia, Pa.). 2007;(6):693-700
Abstract
BACKGROUND To determine short-term effects of topical diclofenac administered in conjunction with verteporfin therapy for predominantly classic subfoveal choroidal neovascularization (CNV) due to age-related macular degeneration (AMD). METHODS Randomized, multicenter (14), prospective, placebo-controlled, double-masked clinical trial. Patients (n=61) were randomly assigned to treatment with diclofenac sodium ophthalmic solution 0.1% or placebo and followed for 12 weeks. Patients instilled diclofenac or placebo two drops four times daily, 2-4 days before verteporfin treatment until 2 weeks after treatment, then two drops twice daily for 10 weeks. This exploratory study was not powered to detect differences between treatment groups. Statistical analyses were conducted solely to aid interpretation of results. RESULTS In diclofenac-treated eyes, mean changes in visual acuity letter score from baseline in the diclofenac and placebo groups were +1.8 letters and -1.0 at week 1 (P=0.505 between groups). Mean visual acuity letter scores decreased in both groups at all subsequent visits, with a mean change at 12 weeks of -7.4 with diclofenac and -2.6 with placebo (P=0.213). Percentages of eyes with stable or improved vision (change or=5 letters) were similar in the diclofenac and placebo groups at all study visits. No significant between-group differences in changes from baseline in lesion area, greatest linear dimension (GLD), fluorescein leakage, or retinal thickness were detected. CONCLUSION In patients with predominantly classic subfoveal CNV due to AMD, administration of topical diclofenac with verteporfin therapy was associated with similar vision outcomes to placebo plus verteporfin therapy.
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10.
Efficacy and tolerability of diclofenac potassium sachets in acute postoperative dental pain: a placebo-controlled, randomised, comparative study vs. diclofenac potassium tablets.
Hofele, CM, Gyenes, V, Daems, LN, Stypula-Ciuba, B, Wagener, H, Siegel, J, Edson, K, ,
International journal of clinical practice. 2006;(3):300-7
Abstract
This double-blind, randomised, parallel-group trial compared the analgesic efficacy of single 50 mg doses of diclofenac potassium sachets and tablets with placebo in 184 patients with moderate/severe pain after third molar extraction. The primary efficacy variable was the average pain reduction from baseline during the first 2-h postdose, using a visual analogue scale (VAS). During the first 2-h postdose, sachets and tablets significantly reduced pain (p < 0.05) vs. placebo with an incremental benefit seen for sachets over tablets (p < 0.05). Onset of analgesic effect (VAS) was at 30 min for sachets and 45 min for tablets. Pain reduction vs. placebo (VAS) was maintained for 8 h for sachets and tablets (p < 0.05). VAS-findings were confirmed by pain relief and intensity verbal scale assessments. Fewer patients re-medicated vs. placebo. No safety issues were identified. This study demonstrates that both diclofenac potassium sachets and tablets offer patients suffering from acute pain conditions an effective treatment with incremental analgesic benefits seen for sachets.