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.     

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.     

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.     

Diflunisal in the management of sprains

Summary

A double-blind randomized trial was carried out in 31 patients suffering from acute, minor ligamentous injuries to compare the efficacy of diflunisal in the relief of pain with that of oxyphenbutazone. Patients received either 500?mg diflunisal twice daily or 200?mg oxyphenbutazone 3-times daily for 3 days. The results of subjective assessments showed that by Day 3 spontaneous pain had either completely resolved or markedly improved in all patients, and that diflunisal was significantly better than oxyphenbutazone on Days 1 and 3 in relieving pain on movement of the joint.     

Diflunisal compared with naproxen in the treatment of osteoarthrosis of hip or knee: a double-blind trial

Summary

A randomized double-blind trial was carried out in 20 patients with osteoarthrosis of the hip or knee to compare the efficacy and tolerance of treatment with diflunisal or naproxen. During the first 4 weeks, patients received either 250?mg diflunisal or 250?mg naproxen twice daily and this was increased by 250?mg daily in 5 patients on diflunisal and in 3 on naproxen for the second 4 weeks of the trial. The results of subjective assessments made before and at the end of Week 8 showed a trend in favour of diflunisal for improvement of symptoms, except for weight-bearing pain which was improved in only 1 patient in each group. More of the patients receiving diflunisal than naproxen considered treatment to have been satisfactory, and rated their response as equally as good as or better than previous medication. Diflunisal produced significantly fewer side-effects than naproxen, the use of which was associated with a relatively high incidence of gastro-intestinal upsets, leading to the withdrawal of 2 patients at Week 4.     

A double-blind comparison of diflunisal and aspirin in the treatment of post-operative pain after episiotomy

Summary

A double-blind randomized trial was carried out in 161 primiparous women suffering from moderate to severe post-episiotomy pain to compare the analgesic efficacy of single doses of diflunisal (125?mg, 250?mg, or 500?mg), aspirin (600?mg), and placebo. The results of pain rating assessments made before and at hourly intervals after drug administration showed that both the active drugs were more effective than placebo and produced similar pain relief over the first 4 hours. The analgesic efficacy of aspirin tailed off after 4 hours but pain relief with 500?mg diflunisal was still evident after 8 hours. Over 65% of patients in the diflunisal group had effective relief of pain at 8 hours whereas there was no significant difference between the aspirin and placebo-treated groups by the seventh and eighth hour.     

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.     

The analgesic and anti- inflammatory efficacy of diflunisal and Codeine after removal of impacted third molars

Summary

A double-blind, randomized trial was carried out in 90 patients to compare the analgesic and anti-inflammatory efficacy of 500?mg diflunisal twice daily with that of 25?mg codeine phosphate 4-times daily and of placebo in relieving pain and swelling after surgical removal of impacted third molars. Diflunisal was found to be superior to codeine and placebo on the first post-operative day, but the difference in efficacy of the drugs had diminished by the third post-operative day. In the diflunisal group of 30 patients, 10 (33%) developed ‘dry socket’ or alveolitis sicca dolorosa. Only 2 patients in the codeine group and 1 patient in the placebo group developed this very painful condition. The possible explanation of ‘dry socket’ is discussed.     

A multiple-dose comparison of ketorolac tromethamine with diflunisal and placebo in postmeniscectomy pain

The efficacy of oral ketorolac 5 mg and 10 mg taken qid was compared in a randomized double-blind study with that of oral diflunisal 500 mg bid (interleaved with placebo twice daily) and of placebo, in 120 patients suffering at least moderate pain following meniscectomy. The trial comprised two phases: (1) an acute phase (the first postoperative day) and (2) a chronic phase (days 2-5 postoperatively). Acutely, pain was assessed before drug administration, and then 0.5, 1.0, 2.0, 3.0, 4.0, 6.0, 8.0, and 9.0 hours after the first dose. The second of the four daily doses was administered at four hours after the first dose. During the chronic phase, pain was assessed using visual analogue scales at 8 AM and 4 PM daily. The acute phase results show that all the active treatments were statistically significantly superior to placebo but were not distinguished from each other. Over the chronic phase, ketorolac 5 mg and placebo showed similar results, with diflunisal showing the least pain relief and ketorolac 10 mg the most. All the active treatments showed a low incidence of side effects and, in an overall evaluation, no one treatment was distinguishable. Ketorolac would seem to be an acceptable therapy for acute postoperative pain.     

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.     

Diflunisal in osteoarthrosis of the hip and knee

Summary

A double-blind randomized trial was carried out in 60 patients with osteoarthrosis of the hip or knee to assess the relative efficacy and tolerance of treatment with diflunisal twice daily (maximum 750?mg per day) or with aspirin given 4-times daily (maximum 3 g per day) over a period of 12 weeks. Clinical assessments were made on entry and at regular intervals of weight-bearing pain, night pain, specific function pain, inactivity stiffness, and range of joint movement. A considerable proportion of patients in both groups showed improvement in all parameters except for limitation of movement. The difference in response between the two groups was not statistically significant, neither was the patients' overall opinion of response to or clinician's assessment of therapeutic efficacy of either drug treatment at the end of the trial. Ten of the 29 patients in the aspirin group had to withdraw because of adverse reactions, mainly gastro-intestinal, compared with 4 of the 31 patients in the diflunisal group. The overall incidence of side-effects in all patients was lower in the diflunisal group, and those that were reported were less disturbing. At the end of the double-blind study, patients were given the option to continue with the particular drug treatment for a further two 13-week periods. More patients chose to remain on diflunisal than on aspirin at the end of each of the three periods and the difference was statistically significant.     

A double-blind comparison of nefopam and placebo in post-operative pain

Summary

Nefopam (90?mg), an analgesic, was compared with placebo in a double-blind trial in patients who had undergone total abdominal hysterectomy operations. Analgesic activity was assessed by patients rating their pain before and 1 hour after administration of each treatment, by sequential analysis of patient and observer preference for treatment, and by calculation of the time interval between doses of the two treatments. Nefopam was found by observer preference to be significantly better than placebo in relieving post-operative pain. In patients with severe initial pain, the time between doses after nefopam was significantly longer than after placebo.     

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

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.     

A placebo-controlled comparative study of sustained-release brompheniramine maleate against clemastine fumarate in the treatment of chronic urticaria

Summary

A partially-blind, three-way crossover study was carried out in 24 patients suffering from chronic urticaria to compare the efficacy and tolerance of brompheniramine maleate with that of clemastine fumarate. Patients received 4-week courses of treatment with 1 tablet twice daily of either 12?mg brompheniramine, 1?mg clemastine or placebo, in random order. Assessments were made by the physician of the patients' condition on entry and of response to treatment at the end of each 2-week period throughout the 12-week study period. At the end of the trial, patients were asked to state their preference, if any, for the different treatments. The results showed that both antihistamines were significantly effective compared to placebo and that at the dosage used brompheniramine was considered significantly better than clemastine in long-term control. Drowsiness was experienced by 4 patients whilst taking brompheniramine compared to 3 patients whilst taking clemastine. One patient experienced anorexia and vomiting with brompheniramine and 4 patients developed gastro-intestinal upsets whilst taking the placebo.     

A controlled comparison of dipyrone and paracetamol in post-episiotomy pain

Summary

A double-blind, placebo-controlled trial was carried out in 299 patients suffering from post-episiotomy pain to compare the analgesic effectiveness and tolerance of single doses of 500?mg dipyrone and 500?mg paracetamol. Assessments of pain relief over a 6-hour period showed that dipyrone produced significantly better results than placebo within half an hour of intake mid maintained this superiority throughout the 6 hours. It also afforded consistently better pain relief than paracetamol and was significantly more effective at the 6-hour assessment. Side-effects were few and mild.     

Diflunisal compared with naproxen in the treatment of osteoarthrosis of hip or knee: a double-blind trial.

A randomized double-blind trial was carried out in 20 patients with osteoarthrosis of the hip or knee to compare the efficacy and tolerance of treatment with diflunisal or naproxen. During the first 4 weeks, patients received either 250 mg diflunisal or 250 mg naproxen twice daily and this was increased by 250 mg daily in 5 patients on diflunisal and in 3 on naproxen for the second 4 weeks of the trial. The results of subjective assessments made before and at the end of Week 8 showed a trend in favour of diflunisal for improvement of symptoms, except for weight-bearing pain which was improved in only 1 patient in each group. More of the patients receiving diflunisal than naproxen considered treatment to have been satisfactory, and rated their response as equally as good as or better than previous medication. Diflunisal produced significantly high incidence of gastro-intestinal upsets, leading to the withdrawal of 2 patients at Week 4.     

Efficacy and safety of mirogabalin for the treatment of fibromyalgia: results from three 13-week randomized,double-blind,placebo- and active-controlled,parallel-group studies and a 52-week open-label extension study

Objective: To investigate the efficacy and safety of mirogabalin, an α₂δ ligand, in patients with fibromyalgia (FM).

Methods: In three 13-week, multicenter, double-blind, phase 3 studies (studies A, B, and C), patients with FM (n?=?1293, 1270, and 1301, respectively) were randomized (1:1:1:1) to placebo, pregabalin 150?mg twice daily, mirogabalin 15?mg once daily or mirogabalin 15?mg twice daily. The primary endpoint was the change in weekly average daily worst pain score (ADPS) at week 13. Key secondary endpoints included Patient Global Impression of Change and change in the Fibromyalgia Impact Questionnaire total score. Long-term safety of mirogabalin was assessed in a 52-week extension study.

Results: Neither mirogabalin dose demonstrated a significant ADPS reduction from baseline vs. placebo at week 13 in any of the three studies. Pregabalin significantly reduced ADPS from baseline vs. placebo in studies B and C (p?=?.0008 and .0001, respectively). The effect of mirogabalin compared with placebo on key secondary endpoints was variable across the studies. Mirogabalin was well tolerated by most patients in the phase 3 studies; no unexpected adverse events occurring during the 52-week extension study.

Conclusion: While both mirogabalin doses were well tolerated by most patients and showed potential for reducing pain associated with FM, the primary endpoint of significant pain reduction in patients on mirogabalin compared with placebo was not achieved in any of the three randomized controlled studies.

Clinical trial registration: NCT02146430; NCT02187159; NCT02187471; and NCT02234583 (extension study).     

Platelet aggregation in patients treated with diflunisal

Summary

The effect of the non-steroidal analgesic diflunisal on platelet aggregation and clinical haemorrhage at a dosage 250?mg twice or 3-times daily, sufficient to relieve musculo-skeletal pain and other painful conditions, was studied in 15 patients and 5 normal subjects. Platelet aggregation was carried out with ADP and collagen before and during treatment with diflunisal. The results indicated that diflunisal is an effective analgesic with no significant adverse effect on platelet function or clinical bleeding.     

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.