Tiapride versus glafenine: a double-blind comparative study in the management of acute rheumatic pain

A double-blind study was carried out in 42 patients suffering from acute rheumatic pain to compare the analgesic effectiveness and tolerance of tiapride with that of glafenine, a widely used analgesic in Europe. Patients were allocated at random to receive either 100 mg tiapride or 200 mg glafenine 3-times daily over a period of 14 days. Pain intensity was rated daily by the patients using a visual analogue scale and an overall assessment of response to treatment was made by both patients and physician at the end of the study. The results showed that, whilst both treatments resulted in a marked reduction in mean pain scores, pain disappeared completely in 16 (76%) of the 21 patients treated with tiapride compared with 9 (43%) of the 21 receiving glafenine. There was also a significant difference in favour of tiapride in the physician's overall assessment of response which was considered as excellent in 71% of the patients on tiapride compared with 31% receiving glafenine. Both treatments were well tolerated and few side-effects were reported. Drowsiness occurred in 6 patients on tiapride but this was only mild in 5 and moderate in the other patient.     

Comparative analgesic efficacy and tolerability of ketorolac tromethamine and glafenine in patients with post-operative pain

Summary

In a randomized, single-dose, double-blind, parallel comparative trial of analgesic efficacy, 96 adult patients received either 10?mg ketorolac tromethamine or 400?mg glafenine orally the morning after surgery if they requested pain relief medication. Each patient provided a baseline pain assessment and then received the assigned medication. Patients assessed pain intensity and pain relief and reported any adverse events in interviews held 30 minutes after drug administration and then hourly for 6 hours. The demographic characteristics, baseline pain intensity, and surgical categories of the 47 patients who received ketorolac tromethamine and the 49 who received glafenine were similar. Both drugs provided prompt, sustained pain relief throughout the 6-hour observation period, and there were no statistically significant differences between the two groups in any of the efficacy measures analyzed. The global assessment recorded by patients suggested a slight clinical advantage for ketorolac tromethamine (32.6% of ‘excellent’ responses) as compared to glafenine (12.5% ‘excellent’). The differences in overall response were statistically significant (p = 0.017). Fourteen (30%) patients who received ketorolac tromethamine and 17 (35%) who received glafenine reported adverse experiences that began or seemed to worsen after administration of the study drugs. The most prominent were drowsiness and sleeping, both of which are common in post-surgical patients.     

Comparative analgesic efficacy and tolerability of ketorolac tromethamine and glafenine in patients with post-operative pain

In a randomized, single-dose, double-blind, parallel comparative trial of analgesic efficacy, 96 adult patients received either 10 mg ketorolac tromethamine or 400 mg glafenine orally the morning after surgery if they requested pain relief medication. Each patient provided a baseline pain assessment and then received the assigned medication. Patients assessed pain intensity and pain relief and reported any adverse events in interviews held 30 minutes after drug administration and then hourly for 6 hours. The demographic characteristics, baseline pain intensity, and surgical categories of the 47 patients who received ketorolac tromethamine and the 49 who received glafenine were similar. Both drugs provided prompt, sustained pain relief throughout the 6-hour observation period, and there were no statistically significant differences between the two groups in any of the efficacy measures analyzed. The global assessment recorded by patients suggested a slight clinical advantage for ketorolac tromethamine (32.6% of 'excellent' responses) as compared to glafenine (12.5% 'excellent'). The differences in overall response were statistically significant (p = 0.017). Fourteen (30%) patients who received ketorolac tromethamine and 17 (35%) who received glafenine reported adverse experiences that began or seemed to worsen after administration of the study drugs. The most prominent were drowsiness and sleeping, both of which are common in post-surgical patients.     

The use of diflunisal in post-operative pain: a report of double-blind Comparative trials in patients after meniscectomy

Summary

A series of double-blind randomized trials was carried out in patients suffering from moderate to severe pain after meniscectomy to assess the analgesic effectiveness of diflunisal. In a single-dose study, 150 patients received either diflunisal (125?mg, 250?mg or 500?mg), aspirin (600?mg), or placebo, and hourly assessments were made of pain severity over an 8-hour period. The results showed that 500?mg diflunisal produced comparable relief to aspirin within 3 to 4 hours, but the analgesic effect continued for longer and was still very marked after 8 hours. A multi-dose study in 120 patients receiving doses of diflunisal (375?mg or 500?mg) or placebo confirmed the overall effectiveness of twice daily treatment with diflunisal. In a comparative study against oxyphenbutazone (200?mg t.i.d.), hourly pain scores made on the first postoperative day showed that a single dose of 500?mg diflunisal produced comparable relief over a 12-hour period to that with 2 doses of 200?mg oxyphenbutazone. Overall response to multiple doses was assessed as excellent or good by all the patients receiving diflunisal. Preliminary results are reported on the use of diflunisal in other painful conditions.     

A controlled study of diflunisal in Sprains and Strains

Summary

A preliminary double-blind, randomized trial was carried out in general practice to compare the efficacy of treatment with diflunisal (500?mg) twice daily and a combination of dextropropoxyphene (65?mg) plus paracetamol (650?mg) 3-times daily for 3 days in relieving pain associated with strains and sprains. Analysis of the results from 51 patients showed that both treatments were equally effective in relieving spontaneous pain and pain on movement after 1 and 3 days, and there were no differences between the two groups in patients' overall evaluation of treatment or physicians' assessment of therapeutic response. Both treatments were well tolerated during the short-term period of the trial.     

Diflunisal in general practice

Summary

A large-scale, double-blind comparative study was carried out in general practice to assess the relative efficacy and tolerance of diflunisal and aspirin in patients suffering from acute painful conditions such as sprains and strains, osteoarthritis, etc. Patients received either 250?mg or 500?mg diflunisal twice daily, or 600?mg aspirin 4-times daily for 5 days. The results of subjective assessments of pain relief from the daily records of 1902 patients (967 on diflunisal, 935 on aspirin), and the overall assessment of response by both doctors and patients, showed that diflunisal was significantly better than aspirin. Gastric side-effects were more common and more severe in patients receiving aspirin, and more often led to withdrawal of treatment.     

Double-blind parallel study of meptazinol versus diflunisal in the treatment of lumbago

Summary

Seventy out-patients with acute back pain participated in a double-blind comparative trial of the clinical efficacy and tolerance of orally administered meptazinol and diflunisal. Half of the patients received 200?mg meptazinol or 250?mg diflunisal 4-times daily for up to 3 weeks, depending on the duration of pain. Patients were examined 4 times at 1-week intervals for their capability to do daily tasks, for their capacity for forward bending, thoraco-lumbar torsion, straight leg raising, static hip flexion and sit-ups, and for subjective assessment of pain. Side-effects were recorded on a questionnaire. Both treatments produced marked improvement in most of the parameters assessed, often within the first week and, overall, the results were similar with the two drugs. Few side-effects were reported and those that were recorded were slight and similar in incidence apart from nausea in 5 meptazinol-treated patients and smarting and burning on urination in 2 patients receiving diflunisal.     

Ibuprofen and Diclofenac Sodium in the Treatment of Osteoarthritis: A Comparative Trial of Two Once-Daily Sustained-Release NSAID Formulations

Summary

An investigator-blind, parallel-group, multicentre study was undertaken to compare the efficacy and tolerability of once-daily, sustained-release (s-r) ibuprofen and diclofenac sodium in patients (mean age 59.8 years) suffering from painful osteoarthritis affecting chiefly the knee and/or hip. Patients attending eight Swiss centres received either two s-r tablets of ibuprofen (daily dose 1600 mg; n = 30) or a single s-r diclofenac 100?mg tablet (n = 31) each evening for 21 days. Clinical assessments were performed prior to initiating therapy and after 7 and 21 days of treatment.

Both treatments were efficacious, but statistically significant differences in favour of s-r ibuprofen were observed for the principal measure of efficacy, the investigator's assessment of the overall change in clinical condition; by Day 21, 37% of ibuprofen-treated patients vs 10% of diclofenac-treated patients were ‘much improved’ (p = 0.04). Patients’ assessments of the efficacy of their treatment also favoured s-r ibuprofen at Day 7 for the relief of night pain (p = 0.048), at Day 21 for alleviation of day pain (p = 0.006) and for the ability to carry out normal activities (p = 0.01), and at both Days 7 and 21 for quality of sleep (p = 0.04 and 0.03, respectively). The patients’ overall opinion of treatment was also significantly in favour of s-r ibuprofen, which was rated ‘good or excellent’ by 80% (24/30), compared with only 38% of patients (11/29) receiving s-r diclofenac sodium (p = 0.002).

Two patients (6%) receiving s-r diclofenac sodium ceased treatment owing to dizziness and severe diarrhoea, respectively; there were no withdrawals in the ibuprofen-treated group. Ten (32%) patients in the s-r diclofenac group reported a total of 12 adverse events (mostly gastrointestinal in nature), compared with three (10%) patients in the s-r ibuprofen group who reported only three events (abdominal pain, insomnia and constipation).

In conclusion, although both NSAID treatments improved the clinical condition of patients with painful osteoarthritis, statistically significant differences in favour of once-daily s-r ibuprofen (1600?mg) were demonstrated in terms of efficacy, indicating a potential therapeutic advantage for this formulation. Ibuprofen was also better tolerated than diclofenac sodium (100?mg/day), the latter being associated with gastrointestinal side effects in a significant proportion of patients. Sustained-release ibuprofen (Brufen Retard®) thus represents an important addition to the available therapeutic armamentarium of once-daily NSAID formulations.     

The efficacy of flurbiprofen versus piroxicam in the treatment of acute soft tissue rheumatism

Summary

Fifty patients suffering from acute soft tissue rheumatism entered an open parallel group study of flurbiprofen 200?mg to 400?mg daily versus piroxicam 20?mg to 40?mg daily for 4 weeks. Both treatments caused statistically significant improvements in pain, pain on active movement, restriction of passive movement and reduction of strength. Global assessments of the patients' progress also improved significantly with both compounds. Flurbiprofen was significantly superior to piroxicam with regard to relief of pain at Day 28, pain on active movement at Days 14 and 28, pain on passive movement at Days 7, 14 and 28 and pain, as measured by a visual analogue scale, at Day 14. Clinically, flurbiprofen showed greater improvements in all the other parameters throughout the study period. Side-effects, mainly gastro-intestinal in nature, occurred in 6 patients receiving flurbiprofen and 8 receiving piroxicam. One patient receiving flurbiprofen was withdrawn due to stomach pain and headache, but no withdrawals due to side-effects were necessary in those receiving piroxicam. One patient receiving piroxicam was withdrawn due to a total remission by Day 14.     

A multi-centre study of zomepirac in painful conditions: An analysis of clinical data for 5819 patients

Summary

An open, multi-centre study was carried out in patients with various moderate to severe painful conditions to assess the effectiveness of zomepirac in relieving pain and improving sleep quality. Patients were treated with 300?mg to 600?mg zomepirac daily for 7 days. Data from 5819 patients have been analyzed so far in the ongoing study. Most of the patients (73%) were already being treated with an analgesic on entry and more than half of them had been prescribed this by their doctor. Almost half, however, had still been in pain for more than 4 weeks before receiving zomepirac. Assessments of pain severity and sleep quality on entry and after treatment indicated that 70% of the patients were considered to have improved, according to the opinion of both doctors and patients, with the best response being observed in those with acute painful states such as sprains, strains and fractures and with pain of short duration. The side-effects reported, which were mainly gastro-intestinal, were mild in general and led to withdrawal of only 7% of the patients before completion of treatment.     

Comparison of slow-release indomethacin and diflunisal in patients with arthrosis

Summary

A double-blind, crossover study was carried out in 44 patients with osteoarthrosis of the hip or knee to compare the efficacy and tolerability of treatment with a new slow-release formulation of indomethacin (50?mg) with that of diflunisal (250?mg). After a 1-week wash-out period, patients were allocated at random to receive 2 tablets daily of one or other preparation for 6 weeks before being crossed over to the alternative drug for a further 6 weeks. Aspirin was allowed as a rescue analgesic throughout the study. Subjective assessments of pain and objective assessments of joint mobility were made before the start of treatment and at the end of each period, and details were recorded of rescue analgesic usage and any side-effects. Analysis of the results from 42 patients showed that whilst both treatments helped to alleviate pain, patients' overall evaluation of efficacy at the end of the study indicated that indomethacin was slightly more effective than dif lunisal and there was a significant preference for indomethacin. Both drugs were well tolerated and none of the side-effects, reported in about 15% of patients on each drug, resulted in any withdrawals.     

Diflunisal in the treatment of osteoarthrosis: a double-blind study comparing diflunisal with ibuprofen

Summary

A double-blind trial was carried out in 37 patients with osteoarthrosis to compare the efficacy and tolerance of 250?mg diflunisal twice daily with that of 400?mg ibuprofen 3-times daily over an 8-week period. Rating scale assessments were made, at the end of a preceding 1-week wash-out period on placebo and at regular fixed intervals, of weight-bearing pain, night pain, a specific functional activity, and of the duration of inactivity stiffness. Patients' and physician's overall evaluations of response, taking side-effects into account, were made on completion of the study. The data collected indicated that in 30 patients completing the trial both treatments produced similar overall results and, with the exception of weight-bearing pain which appeared to be improved more in the ibuprofen group, diflunisal provided equal therapeutic benefit with fewer side-effects.     

Open-label study of the safety and effectiveness of long-term therapy with extended-release tramadol in the management of chronic nonmalignant pain

ABSTRACT

Background: Tramadol ER is a once-daily oral analgesic for management of moderate-to-moderately severe chronic pain in adults who require around-the-clock treatment of pain. This study evaluated long-term safety of tramadol ER and effectiveness outcomes in the management of chronic, nonmalignant pain.

Methods: Patients enrolled directly for approximately 1 year of open-label tramadol ER treatment if they had chronic, nonmalignant pain (n = 919), or ‘rolled over’ for 38 weeks of open-label tramadol ER treatment if they completed either of two 12-week, placebo-controlled studies of tramadol ER for low back pain (n = 72) or osteoarthritis (n = 61). Tramadol ER was titrated to a dose of 300?mg once daily (patients ≥?75 years) or 300–400?mg once daily (patients <?75 years).

Results: A total of 257 (24%) patients completed the study. Common adverse events, regardless of treatment relationship, were nausea, dizziness (excluding vertigo), and constipation. Mean scores for current pain intensity (from 0 = no pain to 100 = extreme pain) and least, worst, and average pain intensity over the past week improved at every post-baseline visit. At each post-baseline visit, >?50% of patients provided a global assessment rating of good, very good, or excellent. Study limitations were mandatory titration to 400?mg in some patients, concomitant analgesic therapy as a confounding variable, and lack of a placebo comparator.

Conclusions: Individualized dose titration and limiting once-daily therapy with tramadol ER to the maximum recommended daily dose of 300?mg may balance tolerability and analgesic effects of tramadol ER in patients with chronic, nonmalignant pain.     

The analgesic effect of etoricoxib relative to that of two opioid-acetaminophen analgesics: a randomized,controlled single-dose study in acute dental impaction pain

ABSTRACT

Background: To compare the analgesic effect of single doses of etoricoxib 120?mg, oxycodone/acetaminophen 10?mg/650?mg and codeine/acetaminophen 60?mg/600?mg in acute pain using the dental impaction model.

Methods: In this randomized, double-blind, placebo-controlled, parallel-group study, patients reported pain intensity and pain relief (16 times) and global scores (twice) during a 24-h period. The primary endpoint was the overall analgesic effect, total pain relief over 6?h (TOPAR6). Other endpoints were patient global evaluation, time to onset (2-stopwatch method), duration of analgesic effect (median time to and amount of rescue medication use). Tolerability was evaluated by overall and opioid-related (nausea and vomiting) adverse experiences.

Results: 302 patients (mean age 23; 63% women; 63 % White) were randomized to etoricoxib 120?mg, oxycodone/acetaminophen 10?mg/650?mg, codeine/acetaminophen 60?mg/600?mg, and placebo (2:2:1:1). Etoricoxib demonstrated significantly greater overall analgesic efficacy (TOPAR6) (13.2?units) versus oxycodone/acetaminophen (10.2?units); and codeine/acetaminophen (6.0?units); p < 0.001 for all. All active treatments were superior to placebo. Median time to onset was significantly (?p < 0.001) shorter for oxycodone/acetaminophen (20?min) and numerically but not significantly shorter (?p = 0.259) for codeine/acetaminophen (26?min) compared with etoricoxib (40?min). Etoricoxib (24?h) had a significantly longer lasting analgesic effect than oxycodone/acetaminophen (5.3?h), codeine/acetaminophen (2.7?h), and placebo (1.7?h) (?p < 0.001 for all). Etoricoxib patients experienced fewer clinical adverse experiences than patients on oxycodone/acetaminophen and codeine/acetaminophen, specifically, significantly (?p < 0.05) fewer episodes of nausea.

Conclusion: Etoricoxib 120?mg provided superior overall analgesic effect with a smaller percentage of patients experiencing nausea versus both oxycodone/acetaminophen 10?mg/650?mg and codeine/acetaminophen 60?mg/600?mg.     

Long-term use of azapropazone in rheumatoid conditions

Summary

In an open assessment of azapropazone, 51 patients with rheumatoid disorders, mainly rheumatoid arthritis, were treated continuously for periods up to 3 years (range 2 weeks to 38 months). Treatment was interrupted or discontinued in 9 patients for various reasons. Initial dosage was 1200?mg. daily, but this was usually reduced after a few months to a maintenance level of 900?mg. daily.

An overall assessment of patient response at the end of the study period indicated that only 4 (7.8 %) of the 51 patients failed to obtain satisfactory relief during treatment: 28 (54.6%) showed objective signs of improvement, such as reduced joint swelling and stiffness, as well as subjective evidence of symptom relief, and a further 19 patients (37.3 %) reported an equivocal analgesic effect with azapropazone.

Few side-effects were reported, mainly mild gastralgia and nausea, and routine laboratory investigations throughout the long-term study revealed no abnormalities in the blood picture, liver or renal function or coagulation factors. There was also no evidence of any interaction between azapropazone and other drugs used concomitantly.     

Cizolirtine Citrate (E-4018) in the Treatment of Chronic Neuropathic Pain

Summary

This study was performed to determine the efficacy and safety of oral cizolirtine citrate, a novel agent, in the treatment of chronic neuropathic pain. Cizolirtine was tested in a double-blind, placebo-controlled, two-way crossover study, having previously been shown to have significant analgesic and anti-hyperalgesic action in neuropathic pain models and preliminary human studies.

Twenty-five patients with neuropathic pain, which was persistent for at least three months, and scored >30?mm on a 100?mm visual analogue scale (VAS), were included. A subgroup of five patients had primary skin allodynia, i.e. pain evoked by non-noxious stimuli in the territory of the injured nerve. Cizolirtine 200?mg or placebo was administered twice daily for a treatment period of 21 days, each separated by a washout interval of 7 days. Assessments of skin allodynia were performed using the graded monofilaments (von Frey hairs) on days 1 (predose), 14 and 21 (90?min postdose). All patients were instructed to maintain a daily pain diary throughout the study. Results showed that the differences in VAS and allodynia scores between cizolirtine and placebo treatments were not significant in the overall analysis (p?>?0.05); cizolirtine was well tolerated. In a subgroup of five patients with primary allodynia, a 53% reduction in VAS score from baseline at rest (p?=?0.007) and 55% on movement (p?=?0.0002) at day 21 was observed with cizolirtine, as compared to 8% at rest (p?=?0.5215) and 13% on movement (p?=?0.4187) with placebo. Similarly, allodynia improved with cizolirtine (p?=?0.03) but not with placebo (p?=?0.9) in this subgroup. Cizolirtine may be effective in primary allodynia after peripheral nerve injury, and a further trial in a larger number of such subjects is warranted.     

Dose Response and Safety of Cizolirtine Citrate (E-4018) in Patients with Pain Following Extraction of Third Molars

Summary

The objectives of this study were to determine the dose response and safety of the oral analgesic cizolirtine citrate (E-4018) in patients with postoperative pain after third molar extraction. This was a placebo-controlled, double-blind, randomised, parallelgroup study. Doses of E-4018 were 50 mg, 100 mg, or 150 mg. The primary outcome measure of efficacy was patient assessment of pain severity, determined from serial visual analogue scales (VAS) over a four-hour investigation period. Other efficacy measures included the number of patients taking escape analgesic and the time before it was taken, and an overall assessment of pain relief on a four-point categorical scale.

There was no significant difference between any of the E-4018 treatment groups and placebo in terms of the AUC for VAS pain scores over time. The percentages of patients who took paracetamol within five hours of their dose were 100%, 95%, 78% and 82% for the placebo, 50 mg, 100 mg and 150 mg E-4018 groups, respectively. The time to first use of paracetamol was significantly different for the 100 mg and 150 mg E-4018 groups compared to placebo. There were 17 adverse events, of which five were possibly related to the study medication (one in the placebo group and four in the 150 mg E-4018 group).

We conclude that there was a dose-related trend in the percentage of patients requiring paracetamol within five hours of their study medication, and in the percentage of patients that recorded the treatment as providing good or excellent treatment of pain. There was, however, no firm evidence of a dose-related analgesic effect over the dose range of Cizolirtine chosen for this study. E-4018 was well tolerated in all patients.     

Efficacy of a new once daily hydromorphone formulation in comparison with twice daily administration in chronic pain: a randomized,double-blind,cross-over study

Objective Efficacy and safety of a novel multiple-unit hydromorphone once daily (HOD) was compared to an established hydromorphone twice daily (HTD) regimen in patients with moderate-to-severe chronic pain.

Design and methods The results from a randomized, double-blind, multicenter, cross-over trial in patients (n?=?37) with chronic malignant or non-malignant pain are reported. The primary efficacy parameter was current pain on 0–100?mm VAS assessed four times daily and prior to intake of rescue medication (immediate-release hydromorphone) throughout the last 5 days with each treatment (after an 8?day build-up period to avoid carry-over effects). Total daily dose of hydromorphone (TDD: 8–32?mg/day) was kept stable during the double-blind treatment phase.

Results The difference observed in mean current pain (?0.92?mm VAS) over the 5?day assessment period between HOD and HTD (28.44?mm vs. 29.36?mm VAS) was found to lack clinical relevance, as the 95% CI (?4.10 to 2.28?mm VAS) did not exceed the prespecified limit for non-inferiority of 9?mm VAS. Results from the full analysis set were consistent with per protocol data confirming robustness, as did the data for 12?h recalled pain assessed at 08:00?h and 20:00?h, showing no significant differences between once and twice daily medication. Both treatments produced effective and stable pain control with only minor day-to-day and intra-day fluctuations. Switching between treatments was suitable, considering both efficacy and safety, as no relevant or significant differences in adverse events were seen (25.0% HOD, 24.3% HTD). Most frequently typical side-effects of opioid therapy were observed, such as nausea, vomiting and headache.

Conclusion Although this study was of short duration and included a limited number of patients, the results confirm that the new HOD is as effective and safe as the established HTD.     

Clinical investigation of the effects of pentoxifylline in patients with severe peripheral occlusive vascular disease

Summary

Pentoxifylline was used in the treatment of 90 patients with atherosclerosis-induced chronic peripheral arterial occlusive disease and diabetic vascular disorders in the lower extremities (clinical Fontaine Stages III and IV) for whom surgical reconstructive treatment was not indicated and who had shown inadequate response to previous therapy. In 20 initially hospitalized patients, treatment was started with pentoxifylline intravenous infusions for 1 week (increased gradually from 500?mg to 1000?mg per day) and afterwards continued for a further 8 weeks by oral administration of the drug (400?mg 3-times daily). In 70 patients, oral treatment (400?mg 2 to 3-times daily) was carried out from the beginning for 3 to 6 months or longer. The majority (74%) of the patients showed good or very good results in respect of the clinical parameters. Pentoxifylline abolished or decreased rest pain and consumption of analgesic drugs, accelerated healing of leg ulcers, produced a statistically significant increase in mean pain-free walking distance (approximately 500%) and reduced concomitant symptoms. Definite improvement was achieved in 16 patients with initial intravenous treatment and in 62 patients on oral therapy alone. Haemodynamic measurements, as well as whole blood viscosity assessment using a middle and high shear rate viscosimeter, revealed only small and insignificant improvements. No essential changes could be found in the chemical blood parameters studied.