fficacy, Safety, and Tolerability of Dihydroergotamine Nasal Spray as Monotherapy in the Treatment of Acute Migraine

Recently, a new nasal spray formulation of dihydroergotamine was developed which facilitates at-home treatment of migraine. We studied the efficacy, safety, and tolerability of dihydroergotamine nasal spray as monotherapy in the acute treatment of classic and common migraine in two, identical, double-blind, randomized, placebo-controlled trials. Of the 229 patients enrolled, 206 (102 dihydroergotamine nasal spray, 104 placebo) were included in the intent-to-treat analyses; 182 treated two headaches and 24 treated one headache. Based on both the patients' and physicians' ratings, dihydroergotamine nasal spray was significantly superior to placebo for reducing the severity of headache pain in both studies, and in relieving nausea in Study 2. The onset of significant efficacy with dihydroergotamine nasal spray compared to that with placebo for both severity of headache pain and relief of nausea occurred at I hour in Study 2 and at 3 hours in Study 1. Dihydroergotamine nasal spray was also significantly superior to placebo for the relief of headache pain in both studies. Based on the physicians' global evaluations of treatment efficacy for headache pain, 71% of the dihydroergotamine-treated patients in Study 2 and 59% of their counterparts in Study 1 were considered to be responders. The dihydroergotamine-treated patients had less newly-occurring vomiting than the placebo-treated patients. The majority of adverse events reported by the dihydroergotamine-treated patients were nasopharyngeal. The results demonstrate the efficacy, safety, and tolerability of dihydroergotamine nasal spray as monotherapy in the treatment of acute migraine attacks.     

Analgesic effects of intranasal butorphanol tartrate administered via a unit-dose device in the dental impaction pain model: a randomized, double-blind, placebo-controlled, parallel-group study

BACKGROUND: Butorphanol tartrate (BT) nasal spray is currently marketed as a multidose spray pump product. However, access to excessive amounts of drug in a single bottle (up to 15 doses) creates the potential for misuse, diversion, and abuse. OBJECTIVE: This study evaluated the efficacy and tolerability of a sterile, unpreserved BT nasal spray administered via a unit-dose device in the treatment of moderate to severe pain after dental impaction surgery. METHODS: This was a single-site, single-dose, randomized, double-blind, placebo-controlled, parallel-group pilot study of unit-dose BT nasal spray 1 and 2 mg compared with vehicle in patients who received standard anesthesia and underwent surgery to remove impacted third molars. When patients reported experiencing moderate or severe postoperative pain, they were assigned to receive the respective treatments in a 2:2:1 ratio. Patients rated pain intensity and pain relief and performed other assessments of analgesic efficacy before dosing and at 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 3, 4, and 6 hours after receipt of study medication. They could request rescue medication from 1 hour after the administration of nasal spray. The primary efficacy variables were summed pain intensity difference (SPID) at 2, 4, and 6 hours after administration of study medication and total pain relief at 6 hours (TOTPAR-6). Vital signs, pulse oximetry, and adverse events were monitored on the same schedule as pain assessments. RESULTS: Thirty men and 30 women were enrolled (mean [SD] age, 22.5 [3.8] years; mean body weight, 168 [41.3] lb) and completed the trial. Pain relief was recorded in most patients within 15 minutes of receiving active treatment. A dose response was observed in SPID scores, with the 2-mg dose of BT providing the greatest response compared with placebo (P < 0.05). Overall, 52 (86.7%) patients requested rescue medication: 22 of 24 (91.7%) in the 1-mg group, 19 of 24 (79.2%) in the 2-mg group, and 11 of 12 (91.7%) in the placebo group. The time to use of rescue medication occurred a median of 75 to 110 minutes after nasal spray dosing. The analysis of TOTPAR-6 showed no significant differences overall or in pairwise comparisons. On the global assessment, 58.3% of patients in each of the active-treatment groups and 83.3% of patients in the placebo group evaluated the study drug as "poor." The unit-dose BT nasal spray was well tolerated, with central nervous system adverse effects being most common in the active-treatment groups compared with placebo (P = 0.029). Dizziness occurred in 11 (45.8%) patients who received BT 1 mg, 14 (58.3%) who received BT 2 mg, and 4 (33.3%) who received placebo; for headache, the corresponding numbers were 11 (45.8%), 7 (29.2%), and 2 (16.7%). There were no significant changes from baseline in vital signs, pulse oximetry, reported nasal irritation, or pathology (eg, irritation, epistaxis, ulceration). CONCLUSIONS: In this small pilot study, sterile BT nasal spray administered via a unit-dose device provided effective postsurgical analgesia in approximately half of patients who had undergone surgery to remove impacted third molars. The results are similar to those of previous studies of BT nasal spray administered via multidose pump for postsurgical analgesia in the dental impaction pain model. The outcomes of this study are limited to the population studied.     

Desmopressin/indomethacin combination efficacy and safety in renal colic pain management: A randomized placebo controlled trial

IntroductionRenal colic is a prevalent cause of abdominal pain in the emergency department. Although non-steroidal anti-inflammatory drugs and opioids are used for the treatment of renal colic, some adverse effects have been reported. Therefore, desmopressin -a synthetic analogue of vasopressin- has been proposed as another treatment choice. In the present study, indomethacin in combination with nasal desmopressin was compared with indomethacin alone in the management of renal colic.MethodsIncluded in the study were 124 patients with initial diagnosis of renal colic and randomized to receive indomethacin suppository (100 mg) with either desmopressin intranasal spray (4 puffs, total dose of 40 micrograms) and or placebo intranasal spray.ResultsAll the included patients were finally diagnosed with renal colic. There was no difference between the two groups in pain at the baseline (p = 0.4) and both treatments reduced pain successfully (p < 0.001). There was no significant difference between the two groups in pain reduction (p = 0.35).ConclusionsWhile there was significant pain reduction in both patients groups, pain reduction of NSAIDs (e.g. indomethacin) in renal colic, does not significantly improve when given in combination with desmopressin.     

Evaluation of the efficacy of intravenous acetaminophen in the treatment of acute migraine attacks: a double-blind, placebo-controlled parallel group multicenter study

The efficacy of intravenous acetaminophen (1000mg) in the treatment of acute migraine attacks as an alternative to parenteral application of lysine acetylsalicylate or triptans was investigated, using a multi-center, randomized, double-blind, placebo controlled study design. Migraine diagnosis was made according to the International Headache Society Classification. Sixty patients were included in three headache outpatient centers (Neurology Departments of the Universities of Regensburg, Münster and München). In the acute migraine attack patients were treated intravenously with either 1000mg paracetamol (acetaminophen) or placebo. The primary end point was pain-free after 2h. Secondary efficacy criteria were pain-free after 24h or pain relief after 2hours and after 24hours. With regard to the efficacy criteria, 37% of patients reported pain relief or painfree after two hours, 12 patients after treatment with acetaminophen and 10 patients after treatment with placebo. Out of these, 3 patients in the acetaminophen and 4 patients in the placebo group were painfree. After 24hours 86% of the patients reported pain relief: 24 treated with acetaminophen and 27 treated with placebo. The results indicate, that 1000mg intravenous acetaminophen is not superior to placebo in treating severe acute migraine attacks.     

10% Lidocaine spray as a local anesthetic in blood gas sampling: A randomized,double-blind,placebo-controlled study

AimRadial artery blood gas sampling is a very common procedure undertaken in the emergency department to evaluate respiratory and metabolic parameters. This intervention causes both anxiety and pain for the patient. Therefore, the current study aimed to examine the analgesic efficacy of lidocaine spray compared to a placebo during radial artery blood gas sampling.MethodsThis study was conducted in the emergency department of a tertiary hospital with a randomized, double-blind, placebo-controlled design. A total of 144 patients were randomly divided into two groups: One group (n = 72) received 10% lidocaine spray and the other (n = 72) was the placebo group. The analgesic efficacy of the 10% lidocaine spray was compared with the placebo group using the Visual Analog Scale (VAS).ResultsIn the evaluation of the analgesic efficacy of the 10% lidocaine spray, the VAS score was 1.5 [interquartile range (IQR): 2.0] for the lidocaine group and 5 (IQR: 2.0) for the placebo group. The role of lidocaine spray in reducing pain was statistically significant compared to the placebo (p = 0.000).ConclusionIn blood gas sampling, 10% lidocaine spray has analgesic efficacy. Therefore, we recommend the use of lidocaine spray while performing arterial blood gas sampling in emergency departments.     

Zolmitriptan 5 mg nasal spray: efficacy and onset of action in the acute treatment of migraine--results from phase 1 of the REALIZE Study

OBJECTIVES: The objective of phase 1 (reported here) of this two-phase study was to assess the efficacy of zolmitriptan 5 mg nasal spray, in terms of ability to provide relief from all migraine symptoms, in a controlled setting, designed to replicate clinical practice. BACKGROUND: Zolmitriptan nasal spray has been shown to be fast acting and highly effective in the treatment of migraine, as assessed using standard endpoints, such as headache response and pain-free rates. METHODS: In the double-blind first phase of the study, patients with migraine were randomized to receive zolmitriptan 5 mg nasal spray or placebo to treat a single migraine attack. Attacks were treated according to patients' normal patterns of use, in order to closely reflect clinical practice; that is, no specific regimen was dictated in terms of time to treatment or at what level of pain intensity the headache should be treated. Patients could take a second dose of study medication or an agreed escape medication if adequate pain relief had not been achieved 2 hours after the first dose. The primary efficacy endpoint was total symptom relief (freedom from pain, nausea, photophobia, and phonophobia) 1 hour after the first dose. Secondary efficacy endpoints included headache response, pain-free status and sustained pain-free status, and ability to perform normal activities. RESULTS: The intention-to-treat population comprised 461 zolmitriptan nasal spray recipients and 451 placebo recipients. The total symptom relief rate 1 hour post-dose was significantly higher in the zolmitriptan 5 mg nasal spray group than in the placebo group (14.5% vs. 5.1%; P < .0001); the difference between the groups was significant from 30 minutes post-dose. Treatment with zolmitriptan nasal spray, compared with placebo, also produced a higher headache response rate from 10 minutes post-dose (15.1% vs. 9.1%; P = .0079) and a higher pain-free rate from 30 minutes post-dose (7.7% vs. 3.2%; P = .0039). Zolmitriptan nasal spray was also significantly superior to placebo in terms of sustained pain-free status and patients' ability to perform normal activities. Zolmitriptan nasal spray was well tolerated. CONCLUSIONS: These findings confirm the efficacy demonstrated by zolmitriptan nasal spray in previous clinical trials.     

Primary dysmenorrhea treated with indomethacin.

Primary dysmenorrhea is a difficult entity to treat, and therapy is usually directed at relieving symptoms. There is some indication that this disorder is caused by an increase in prostaglandin F2alpha. Therefore, logically the treatment may include antiprostaglandin agents. We have studied 32 women with the diagnosis of primary dysmenorrhea in a randomized double-blind fashion using a placebo and indomethacin. Both agents were taken three times a day over four cycles, and therapy was begun two days before the usual onset of pelvic pain. Only two of 16 patients in the placebo group were significantly improved in the four-month treatment cycles while all 16 in the treatment group showed some improvement, 11 having cessation of pain. In the six months following the study period, all patients were given indomethacin. The original treatment group did not change significantly. However, all in the placebo group when switched to indomethacin had some relief, 12 of the 16 showing complete cessation of pain. Gastric irritation was the main side effect and was present in 18% of the treatment group and 12% in the placebo group. Indomethacin appears to effectively relieve primary dysmenorrhea and does not appear to be associated with a high incidence of side effects.     

Is gabapentin an effective treatment choice for hemicrania continua?

The objective of this study is to examine the efficacy of gabapentin for the treatment of hemicrania continua (HC) in cases where patients had difficulty tolerating indomethacin due to adverse effects. A retrospective chart review of nine patients with HC between October 2006 and February 2008. Inclusion criteria included men and women age 18 or above presenting to the headache center with a headache that meets International Headache Society criteria for HC including a response to indomethacin, but were not able to continue on indomethacin secondary to adverse effects. Four patients report being pain free, three patients report a 50–80% reduction of pain, one patient reports a 10% reduction of pain, and one patient reports no change in pain. Seven out of nine patients demonstrated at least a 50% reduction of pain on gabapentin, four patients becoming completely pain free.     

Eletriptan in the early treatment of acute migraine: influence of pain intensity and time of dosing

This double-blind, placebo-controlled study was designed to evaluate the efficacy and tolerability of early treatment of a single migraine attack, when headache pain was mild, with two doses (20 mg and 40 mg) of eletriptan. Patients (N = 613; female 79%; mean age 39 years) meeting International Headache Society criteria for migraine were encouraged, but not required, to utilize early treatment, thus providing an opportunity to assess the relative contribution to efficacy of pain severity and timing of dose. For the total patient sample (mild-to-severe headaches), 2-h pain-free rates were significantly higher than placebo (22%) on both eletriptan 20 mg (35%; P < 0.01) and eletriptan 40 mg (47%; P < 0.0001). For the cohort of patients who treated their headache when the pain intensity was mild, the 2-h pain-free rate on eletriptan 40 mg was 68% compared with 25% on placebo (P < 0.0001). Pain intensity at the time of taking eletriptan appeared to influence outcome more than the timing of the dose relative to headache onset. Eletriptan was well-tolerated, with adverse event rates similar to placebo when mild headaches were treated.     

Consistent efficacy and tolerability of almotriptan in the acute treatment of multiple migraine attacks: results of a large, randomized, double-blind, placebo-controlled study

In this double-blind study, the efficacy and tolerability of a single dose of almotriptan (6.25 or 12.5 mg) was compared with placebo in the treatment of three consecutive migraine attacks of moderate or severe intensity. Of 1013 randomized patients, 722 evaluable patients completed the study. The total number of attacks relieved (severe or moderate pain reduced to mild or no pain) at 2 h post-dose was significantly higher (P < 0.001) after treatment with almotriptan 6.25 or 12.5 mg compared with placebo (60% and 70% vs. 38%, respectively). Moreover, a consistent response was achieved across and within patients for almotriptan 6.25 or 12.5 mg compared with placebo (pain relief in at least two out of three attacks within 2 h for 64% and 75% vs. 36%, respectively) and less than one-third of the patients relapsed within 24 h. Almotriptan was well tolerated with no significant differences between the almotriptan and placebo treatment groups in the percentage of patients reporting adverse events. Overall, the 12.5-mg dose was associated with the most favourable efficacy/tolerability ratio and is, therefore, the recommended dose.     

Efficacy and tolerability of intranasal fentanyl spray 50 to 200 μg for breakthrough pain in patients with cancer: A phase III,multinational, randomized,double-blind,placebo-controlled,crossover trial with a 10-month,open-label extension treatment period

Objective: This trial investigated the efficacy and long-term tolerability of intranasal fentanyl spray (INFS) 50 to 200 μg in the treatment of breakthrough pain in opioid-tolerant patients with cancer.Methods: This Phase III, double-blind, randomized, placebo-controlled, crossover trial was conducted at pain centers, anesthesiology departments, palliative care units, and oncology clinics in Austria, Denmark, France, Germany, and Poland. Eligible patients were adults with cancer receiving a stable dose of long-term opioid treatment for the control of background pain. Patients were treated at home with their effective dose of INFS (50, 100, or 200 μg) or inactive spray (placebo) in a randomized sequence for 3 weeks, followed by a 10-month, open-label tolerability phase during which they received their effective dose of INFS. Throughout the study, patients were allowed to use their usual rescue medication, which was recorded in patient diaries. The primary efficacy end point was the pain intensity difference at 10 minutes after study drug administration (PID₁₀), as assessed using an 11-point numeric rating scale (0 = no pain to 10 = worst pain imaginable). An effect size of 0.5 for PID was considered clinically relevant. The rate of response, defined as PID₁₀ >2, was also assessed. Adverse events (AEs) were recorded in patient diaries during the efficacy period and reported in monthly clinic visits and follow-up weekly telephone contacts during the extension period.Results: In all, 120 patients were enrolled and achieved an effective dose; 113 were randomized and 111 were included in the intent-to-treat analysis set (56 men, 55 women; mean [SD] age, 60.6 [9.45] years; mean weight, 70.3 kg [men] and 65.3 kg [women]; white race, 107 [96.4%]; INFS 50 μg, 18; INFS 100 μg, 48; INFS 200 μg, 45; placebo, 110). PID₁₀ with INFS was 2-fold that with placebo (adjusted means, 2.36 vs 1.10; adjusted difference, 1.26 [greater than the clinically relevant difference of 0.5]; P < 0.001). Additional analysis revealed that the mean response rate with all 3 doses of INFS was 51.1% versus 20.9% with placebo. The prevalence of AEs was 22/111 (19.8%) during the efficacy period, during which the most frequently reported AEs were nausea (5 [4.5%]) and vertigo (2 [1.8%]). No serious AEs were considered related to the study drugs. In all, 108 patients entered the extension period, with a mean duration of exposure to INFS of 134.9 days. Progression of underlying malignant disease was the most common AE reported during this period (55 [50.9%]); this event was not considered treatment related.Conclusions: In these opioid-tolerant patients with cancer, INFS at doses of 50, 100, and 200 μg was associated with an onset of activity at 10 minutes and effective treatment of breakthrough pain compared with placebo. All doses were generally well tolerated and clinically efficacious.     

Randomized controlled trial of the combined monoaminergic and opioid investigational compound GRT9906 in painful polyneuropathy

GRT9906 is an investigational novel compound with μ‐opioid receptor agonism and inhibition of noradrenalin/serotonin re‐uptake. In this randomized, double‐blind, placebo‐controlled, three‐way cross‐over trial in painful polyneuropathy, the efficacy and safety of GRT9906 was assessed and compared with tramadol. During 4‐week treatment periods, daily oral doses of either GRT9906 120–240 mg, or placebo, or tramadol 200–400 mg were given. These were separated by 1‐week washout periods. The primary endpoint was the average pain intensity (average of daily current pain intensity over the last 3 days of each treatment period rated on a 0 to 10‐point numeric rating scale). One hundred seventeen patients were enrolled and 64 were randomized to one of six treatment sequences. Forty‐seven patients qualified for the per protocol analysis. GRT9906 reduced average pain intensity by 2.1 points compared with a reduction of 0.6 points on placebo (p < 0.0001) and 2.4 points on tramadol. GRT9906 also improved scores on the sleep problem scale and the neuropathic pain symptom inventory and scored better than placebo on the patient global impression of change. Numbers needed to treat to obtain one patient with more than 50% pain relief was 3.9 (95% CI 2.4–11.5) for both GRT9906 and tramadol. The most frequently reported adverse events were nausea, fatigue, constipation and sleep disorder for GRT9906 and tramadol. Four patients dropped out due to adverse events during both GRT9906 and tramadol treatment and two dropped out during placebo treatment. In conclusion, in painful polyneuropathy, GRT9906 demonstrated analgesic efficacy with a magnitude of effect comparable with tramadol and was well tolerated.     

A Pilot Study of Potassium Supplementation in the Treatment of Hypokalemic Patients With Rheumatoid Arthritis: A Randomized, Double-Blinded, Placebo-Controlled Trial

Patients with rheumatoid arthritis (RA) have been described as having significantly low serum potassium concentrations than that in healthy subjects. We assessed the therapeutic efficacy and tolerability of oral potassium supplement dissolved in grape juice in female hypokalemic patients with active RA. Thirty-two hypokalemic patients with active RA were investigated in a parallel, randomized design. In addition to their usual medication, the control group received placebo and the intervention group received 6000 mg chloride potassium dissolved in grape juice on 28 consecutive days. The primary outcome parameter was the change of pain on a visual analog scale (VAS). The American College of Rheumatology (ACR) percent response criteria and Disease Activity Score 28 (DAS28, 28-joint count) and the European League Against Rheumatism (EULAR) moderate response were assessed. Mean age was 48.6 ± 6 years. In the potassium group, 43.75% (7/16) of the patients met the criteria of 33% lower pain intensity compared with 6.25% (1/16) in the placebo group (P < .02) at day 28. Also, 31.25% (5/16) of the patients in the intervention group achieved moderate responses, according to the EULAR criteria. The corresponding percentage for patients receiving placebo was 6.25% (1/16) (P < .05). Potassium supplements appeared to decrease pain intensity.

Perspective

This article reports a trial evaluating the effect of potassium supplementation in the treatment of pain in hypokalemic patients with rheumatoid arthritis. The elevated serum cortisol and potassium values in the treatment group correlate negatively with patient's assessment of pain intensity, reflecting an anti-pain effect for potassium supplementation.     

Gabapentin in traumatic nerve injury pain: a randomized, double-blind, placebo-controlled, cross-over, multi-center study

A double-blind, randomized, placebo-controlled cross-over multi-center study was conducted to evaluate the efficacy and safety of gabapentin in the treatment of neuropathic pain caused by traumatic or postsurgical peripheral nerve injury, using doses up to 2400 mg/day. The study comprised a run-in period of two weeks, two treatment periods of five weeks separated by a three weeks’ washout period. The primary efficacy variable was the change in the mean pain intensity score from baseline to the last week of treatment. Other variables included pain relief, health related quality of life (SF-36), interference of sleep by pain, Clinician and Patient Global Impression of Change, and adverse effects. Nine centers randomized a total of 120 patients, 22 of whom withdrew. There was no statistically significant difference between the treatments for the primary outcome efficacy variable. However, gabapentin provided significantly better pain relief (p = 0.015) compared with placebo. More patients had at least a 30% pain reduction with gabapentin compared with placebo (p = 0.040) and pain interfered significantly less with sleep during gabapentin treatment compared with placebo (p = 0.0016). Both the Patient (p = 0.023) and Clinician (p = 0.037) Global Impression of Change indicated a better response with gabapentin compared with placebo. Gabapentin was well tolerated. The most common adverse effects were dizziness and tiredness.     

Zolmitriptan nasal spray exhibits good long-term safety and tolerability in migraine: results of the INDEX trial

BACKGROUND: Previous studies have shown that zolmitriptan 5 mg nasal spray has a fast onset of action, high efficacy, and good tolerability in the acute treatment of migraine. Objective.-This open-label, noncomparative, multicenter, multinational phase III study was designed to further evaluate the long-term safety and tolerability of zolmitriptan 5 mg nasal spray in a population of migraineurs largely naive to triptan nasal sprays who treated multiple migraine attacks over a 1-year period. METHODS: Patients were required to have an established diagnosis of migraine with or without aura (based on International Headache Society criteria), a high frequency of migraine attacks, and were allowed to treat migraine with any baseline headache intensity. A secondary objective of the study was to assess the long-term efficacy of zolmitriptan nasal spray. A subgroup analysis aimed to determine whether rhinitis had any influence on outcomes of treatment. RESULTS: The safety population consisted of 538 patients who treated 20,717 migraine attacks with zolmitriptan 5 mg nasal spray. Overall, adverse events occurred in 32.8% of attacks, and led to treatment withdrawal in 4.5% of patients. The most common adverse events were unusual taste (19.0%) and paresthesia (6.8%). Adverse events were generally of mild intensity, transient, and well tolerated, showing a decline in incidence over time. Serious adverse events were rare. The presence of rhinitis and use of a second dose of trial medication had no effect on the incidence of adverse events. At 2 hours, 53.8% of attacks treated with zolmitriptan nasal spray 5 mg were rendered pain free. The highest 2-hour pain free rates were seen for headaches of mild baseline intensity (83.3%), followed by headaches of moderate (56.5%), and severe (32.2%) baseline intensity. The 2-hour pain-free rate remained consistent throughout the study period. The presence of rhinitis had no effect on efficacy. CONCLUSIONS: Zolmitriptan 5 mg nasal spray demonstrated a well-tolerated and efficacious profile in the acute treatment of multiple migraine attacks over a 1-year period.     

A randomized, double-masked, clinical study of the efficacy of four nonsteroidal anti-inflammatory drugs in pain control after excimer laser photorefractive keratectomy

OBJECTIVE: This study assessed the efficacy of 4 nonsteroidal anti-inflammatory drugs (NSAIDs) after excimer laser photorefractive keratectomy (PRK). BACKGROUND: Inadequate control of pain after PRK surgery can be a severe source of distress to patients and can interfere with their willingness to undergo a second PRK procedure. METHODS: This randomized, double-masked, placebo-controlled clinical study was conducted in 125 patients. Four NSAIDs (diclofenac, flurbiprofen, ketorolac, and indomethacin) were tested against a placebo group (artificial tears). Pain levels after PRK were quantified using Present Pain Intensity (PPI) and Pain Rating Indices based on rank values (PRI[R]) scores, both of which were calculated using patient responses to a modified McGill Pain Questionnaire. The PRI(R) consisted of 4 subscales-sensory (S), affective (A), evaluative (E), and miscellaneous (M)-as well as a total score (T). RESULTS: Three hours after PRK, no differences in PPI scores were found between the ketorolac, diclofenac, and indomethacin groups, whereas placebo was significantly less effective than the NSAIDs. Patients who received flurbiprofen reported PPI scores that were significantly lower (P < 0.001) than those of patients who received diclofenac and indomethacin, but PPI scores in the flurbiprofen and the ketorolac groups did not differ significantly. Twenty-four hours after surgery, patients treated with flurbiprofen, ketorolac, and diclofenac reported the lowest PPI scores compared with those treated with indomethacin and placebo (P < 0.001). Moreover, flurbiprofen-treated patients also had the lowest PRI(R)T scores (P < 0.001). When the pain rating index was examined by subclass, a significantly lower PRI(R)S score was detected in the flurbiprofen group at 24 hours (P < 0.001). The PRI(R)A score was significantly higher in the placebo and indomethacin groups compared with the other groups (P < 0.001). At the 48- and 72-hour time points, flurbiprofen-treated patients again reported significantly lower PPI and PRI(R)T scores (P < 0.001 for both) in pair-wise comparisons with the other treatment groups. The number of patients who self-administered additional oral analgesics did not differ significantly between the groups. However, the mean number of analgesic tablets used was significantly higher in the placebo group than in any NSAID group (P < 0.001). The ketorolac group had the largest number of patients complaining of itching (P < 0.043). No other subjective symptoms were significantly different across groups. Finally, all NSAIDs, except flurbiprofen, prolonged the mean reepithelialization period slightly (P < 0.001). CONCLUSIONS: Flurbiprofen appeared to be the most effective NSAID for the treatment of pain, even at 24 hours after surgery when pain was at a maximum.     

Efficacy and safety of intravenous acetylsalicylic acid lysinate compared to subcutaneous sumatriptan and parenteral placebo in the acute treatment of migraine. A double-blind, double-dummy, randomized, multicenter, parallel group study

Two-hundred-and-seventy-eight patients with acute migraine attacks with or without aura were treated in 17 centers with 1.8 g lysine acetylsalicylate i.v. (Aspisol®;=1 g acetylsalicylic acid), 6 mg sumatriptan s.c. or placebo using a double-blind, double-dummy, randomized, multicenter parallel group study design. Two-hundred-and-seventy-five of them fulfilled the criteria for efficacy analysis, corresponding to 119 patients treated with lysine acetylsalicylate (L-ASA), 114 with sumatriptan and 42 with placebo injections. Both treatments were highly effective compared to placebo ( p <0.0001) in decreasing headache from severe or moderate to mild or none (verbal rating scale, VRS, placebo=23.8%). Sumatriptan showed a significantly ( p =0.001) better response (91.2%) compared to L-ASA (response 73.9%). Of the patients in the L-ASA-group, 43.7% were pain-free after 2 h; 76.3% after sumatriptan and 14.3%, after placebo. It took patients on average 12.6 (L-ASA), 8.2 (sumatriptan), and 19.4 h (placebo) to be able to work again. There was no significant difference between treatment groups in recurrence of headache in responders within 24 h (18.2% L-ASA, 23.1%, sumatriptan, 20% placebo). Accompanying symptoms (nausea, vomiting, photophobia, phonophohia, and visual disturbances) improved with both verum treatments to a similar extent. L-ASA was significantly better tolerated than sumatriptan (adverse events L-ASA 7.6%, sumatriptan 37.8%). In conclusion, subcutaneous sumatriptan and lysine acetvlsalicylate i.v. are effective treatments for patients suffering from migraine attacks. Sumatriptan is more effective, but resulted in more adverse events.     

Double-blind parallel study of piroxicam versus indomethacin in the treatment of low back pain

Twenty-eight outpatients with chronic severe lumbar pain participated in a double-blind comparative trial on the clinical efficacy of orally administered piroxicam and indomethacin. Half of the patients received indomethacin, 25 mg t.i.d.; the other half received piroxicam 20 mg in the morning and a placebo at lunchtime and before dinner for six weeks. The patients were examined four times at two-week intervals for their capability to do daily tasks and for total lumbar mobility, forward bending, raising of both legs straight and the subjective assessment of pain. Side effects were recorded on a questionnaire and with laboratory tests. The overall results of both groups were similar. Thus, piroxicam, 20 mg daily, matches indomethacin, 25 mg t.i.d., in the treatment of low back pain. The side effects were slight. Treatment with indomethacin was stopped in one case (erythema and conjunctivitis). In the piroxicam group diarrhea, constipation, and pain in the tongue were reported, whereas in the indomethacin group gastrointestinal irritation and tiredness were typical symptoms.     

Placebo-controlled comparison of effervescent acetylsalicylic acid, sumatriptan and ibuprofen in the treatment of migraine attacks

Acetylsalicylic acid (ASA) in combination with metoclopramide has been frequently used in clinical trials in the acute treatment of migraine attacks. Recently the efficacy of a new high buffered formulation of 1000 mg effervescent ASA without metoclopramide compared to placebo has been shown. To further confirm the efficacy of this new formulation in comparison with a triptan and a nonsteroidal anti-inflammatory drug (ibuprofen) a three-fold crossover, double-blind, randomized trial with 312 patients was conducted in Germany, Italy and Spain. Effervescent ASA (1000 mg) was compared to encapsulated sumatriptan (50 mg), ibuprofen (400 mg) and placebo. The percentage of patients with reduction in headache severity from moderate or severe to mild or no pain (primary endpoint) was 52.5% for ASA, 60.2% for ibuprofen, 55.8% for sumatriptan and 30.6% for placebo. All active treatments were superior to placebo (P < 0.0001), whereas active treatments were not statistically different. The number of patients who were pain-free at 2 h was 27.1%, 33.2%, 37.1% and 12.6% for those treated with ASA, ibuprofen, sumatriptan or placebo, respectively. The difference between ASA and sumatriptan was statistically significant (P = 0.025). With respect to other secondary efficacy criteria and accompanying symptoms no statistically significant differences between ASA and ibuprofen or sumatriptan were found. Drug-related adverse events were reported in 4.1%, 5.7%, 6.6% and 4.5% of patients treated with ASA, ibuprofen sumatriptan or placebo. This study showed that 1000 mg effervescent ASA is as effective as 50 mg sumatriptan and 400 mg ibuprofen in the treatment of migraine attacks regarding headache relief from moderate/severe to mild/no pain at 2 h. Regarding pain-free at 2 h sumatriptan was most effective.     

Flurbiprofen in the symptomatic management of rheumatoid arthritis: a valuable alternative

BACKGROUND: The withdrawal of certain cyclooxygenase-2 selective drugs and the availability of over-the-counter non-steroidal anti-inflammatory drugs (NSAIDs) have increased the pressure for researching and prescribing conventional NSAIDs with a favourable efficacy/tolerance ratio in inflammatory diseases, particularly rheumatoid arthritis. The aim of this comprehensive meta-analysis was to evaluate the absolute and relative efficacy and safety of flurbiprofen in the management of rheumatoid arthritis. METHODS: A systematic and exhaustive bibliographic research of published literature has been performed. The inclusion criteria are summarised as follows: randomised trial and rheumatoid arthritis and flurbiprofen and oral administration and anti-inflammatory doses from 100 to 300 mg and (placebo or aspirin or indomethacin or naproxen or ibuprofen or ketoprofen) and (articular pain or stiffness or swelling or mobility or patient/physician reported efficacy or tolerance or gastrointestinal (GI) tolerance). Studies were conducted from January 1975 to January 2006. Analyses have been stratified by comparisons and outcomes. Publication bias and robustness have been extensively investigated. RESULTS: Fourteen studies, accounting for 1103 patient-years, have been included in the quantitative review. The mean daily doses administrated were 200 mg flurbiprofen, 4000 mg aspirin, 150 indomethacin, 750 mg naproxen and 1800 mg ibuprofen. Flurbiprofen was superior to placebo for all outcomes, and superior to three of four other NSAIDs in terms of formal symptomatic measures (pain, stiffness and swelling). Several patients or physicians reported the efficacy of flurbiprofen as superior to indomethacin and naproxen, while its safety, and particularly its GI tolerance were better compared with aspirin and indomethacin. Sensitivity analyses have reported a sufficient robustness against systematic publication bias assumptions. CONCLUSION: This meta-analysis has shown that flurbiprofen is an interesting alternative to commonly prescribed NSAIDs in the symptomatic management of rheumatoid arthritis, especially given its favourable efficacy/tolerance ratio.