Global Evaluation Of Efficacy Research Articles

Canadian trial of sublingual swallow immunotherapy for ragweed rhinoconjunctivitis

Sublingual swallow immunotherapy has been increasingly recognized as a safe and efficacious alternative to parenteral specific immunotherapy. To determine the safety and efficacy of sublingual swallow immunotherapy ragweed allergen extract for rhinoconjunctivitis treatment starting just before and continuing through the ragweed pollen season. This randomized, double-blind, placebo-controlled study was performed in children and adults with a documented history of allergic rhinoconjunctivitis during ragweed season at 9 Canadian allergy centers. Active treatment was standardized extract of ragweed allergen administered as sublingual swallow drops at increasing doses starting shortly before the pollen season and maintenance doses continued daily during the season. Primary efficacy variables were symptom and medication scores, and secondary variables included global evaluation of efficacy and immunologic measurements. Eighty-three patients were included in the safety analysis; 76 patients were included in the intent-to-treat analysis. Nine placebo recipients and 1 treatment recipient withdrew for lack of efficacy (P = .004). Nine patients in the treatment group withdrew because of adverse events, none serious (P = .003). Investigator evaluation of efficacy showed that significantly more patients improved and fewer deteriorated in the treatment group vs the placebo group (P = .047). Ragweed IgE and IgG4 levels increased significantly in treatment recipients vs placebo users (P < .001). Sneezing and nasal pruritus approached significant improvement in the treatment group vs the placebo group (P = .09 and .06, respectively). Quebec City experienced low pollen counts. Excluding Quebec City, significant improvement was seen for these 2 symptoms (P = .04). Sublingual swallow immunotherapy seems to be safe and efficacious for ragweed rhinoconjunctivitis even when started immediately before the ragweed pollen season.

Topical treatment of chronic low back pain with a capsicum plaster

The efficacy and tolerance of a capsicum plaster in non-specific low back pain was investigated in a double-blind, randomised, placebo-controlled multicentre parallel group study. A total of 320 patients were randomly assigned to two groups of n=160 subjects treated by the active or the placebo plaster. The main outcome measures used were a compound pain subscore of the Arhus low back rating scale (continuous variable), and a response criterion of a reduction in pain subscore=30% from baseline to final assessment (secondary, non-continuous variable). In addition, the partial pain scores, disability and mobility restriction subscores, the total score of the Arhus low back rating scale, the global evaluation of efficacy by investigator and patient, adverse events, a patient questionnaire on use of the plaster, and an evaluation of tolerance by investigator and patient were obtained. After 3 weeks treatment with capsicum and placebo plaster respectively, the compound pain subscore was reduced by 42% (capsicum) and 31% (placebo) from values on entry. Responder rate was 67% versus 49% ( p=0.002). The investigators rated efficacy as “excellent” or “good” by 74% and 36%; the patient's efficacy rating “symptomfree” or “improved” reached 82% and 50%. Adverse local drug reactions were found in 12 patients (7.5%) on capsicum and 5 (3.1%) on placebo. No systemic side-effects were observed. The superiority of the treatment of chronic non-specific low back pain with capsicum plaster compared to placebo was clinically relevant and highly statistically significant. The capsicum plaster offers a genuine alternative in the treatment of non-specific low back pain.

Lowest Effective Single Dose of Diclofenac for Antipyretic and Analgesic Effects in Acute Febrile Sore Throat

To compare the antipyretic and analgesic effects of a single oral dose of diclofenac potassium 6.25, 12.5 or 25mg with paracetamol 1000mg and placebo in patients with fever resulting from acute febrile sore throat. This was a multicentre, double-blind, double-dummy, randomised, placebo-controlled, parallel group study conducted at 21 primary-care centres throughout France. In total, 343 adult patients with acute febrile sore throat (fever >/=38.0 degrees C) were randomised to the five treatment groups. Patients received one oral dose of medication. Fever, spontaneous throat pain and pain on swallowing were recorded over 6 hours. If acute symptoms persisted 2 hours after study drug administration, the patient was allowed to take rescue medication and discontinue the trial. The antipyretic effects of diclofenac potassium 6.25, 12.5 and 25mg and paracetamol 1000mg were significantly greater than placebo. The antipyretic effects of diclofenac potassium 12.5 and 25mg were numerically greater than paracetamol 1000mg, which was comparable to the effect of diclofenac potassium 6.25mg. The analgesic effects of the higher doses, diclofenac potassium 12.5 and 25mg, and of paracetamol 1000mg were significantly better than placebo. Summary efficacy measures over the first 4 hours post-dose showed a dose-response relationship among the diclofenac doses, with statistically significant differences on some outcomes between the 25mg and the 6.25mg doses. On the global efficacy evaluation for relief of fever and throat pain, patients rated both diclofenac potassium 12.5 and 25mg significantly higher than paracetamol 1000mg (p </= 0.01). In contrast, paracetamol 1000mg and diclofenac 6.25mg were not rated significantly higher than placebo. Diclofenac potassium was well tolerated, with a safety profile comparable to that of placebo, and slightly favourable compared with that of paracetamol. Diclofenac potassium administered as single doses of 12.5 and 25mg significantly reduced fever and throat pain in patients with acute febrile sore throat. The overall efficacy of these doses was rated significantly higher than that of paracetamol 1000mg or placebo. A dose-response relationship was seen between placebo and the three diclofenac doses. On most outcomes, paracetamol 1000mg was similar to or only slightly better than the diclofenac potassium 6.25mg dose. Diclofenac potassium 12.5mg is the lowest unit dose that could be recommended to provide reliable reduction of oral temperature and relief of throat pain.

Efficacy of a motilin receptor agonist (ABT‐229) for the treatment of gastro‐oesophageal reflux disease

ABT-229 is a potent motilin agonist without significant antibiotic activity. It has been shown to improve gastric emptying in humans and to increase lower oesophageal sphincter pressure in cats. To assess the efficacy of four different doses of ABT-229 (1.25 mg, 2.5 mg, 5 mg, 10 mg b.d.) compared to placebo in the treatment of gastro-oesophageal reflux disease, and to determine its safety in patients with gastro-oesophageal reflux disease. In a double-blind, multicentre study, 324 patients with heartburn were randomized to receive four different doses of ABT-229 or placebo for 8 weeks. The efficacy was evaluated by Patient Symptom Questionnaire, daily diary, endoscopy and global evaluation of efficacy. There were no statistically significant improvement scores for any of the ABT-229 treatment groups vs. the placebo group in any of the efficacy parameters. Reflux symptom scores were significantly worse after treatment in the dyspeptic group. ABT-229 appeared to be well tolerated and safe in total daily doses up to 20 mg. ABT-229 appears to have limited, if any, clinical utility in the treatment of gastro-oesophageal reflux disease.

Therapeutic drug monitoring of selective serotonin reuptake inhibitors influences clinical dosing strategies and reduces drug costs in depressed elderly patients.

This study was initiated in order to describe and evaluate the effects of a therapeutic drug monitoring (TDM) routine of selective serotonin reuptake inhibitors (SSRIs) on treatment strategies and drug costs in depressed elderly patients. Blood samples were drawn from elderly depressed patients and analysed for steady-state trough serum concentrations of citalopram (n = 48), paroxetine (n = 48) or sertraline (n = 39). A global efficacy evaluation was made at baseline and after 6-9 months. Antidepressant drug costs before and after TDM were estimated. Eight samples were excluded due to technical problems or noncompliance. In 65 of the 127 (51.2%) remaining cases, the treatment strategy was changed according to the TDM outcome, in most a reduction of the prescribed dose. Bioanalytical TDM costs included the antidepressant drug costs after TDM were reduced by 10.2%. The results support the utility of TDM in the search for the individual minimum effective SSRI dose in the elderly.

A COMPARISON OF NIMESULIDE BETA CYCLODEXTRIN AND NIMESULIDE IN POSTOPERATIVE DENTAL PAIN

SUMMARYThe aim of this study was to assess the efficacy and tolerability of single doses of nimesulide beta cyclodextrin compared with nimesulide in patients with dental pain following surgical procedures. This was a randomised, double‐blind, between‐patient, multicentre study involving 148 outpatients suffering from moderate to severe pain, who received single doses of either 400 mg nimesulide beta cyclodextrin or 100 mg nimesulide. The principal criterion for efficacy was pain intensity assessed on a visual analogue scale (VAS) 15 minutes after drug intake. Pain intensity was further evaluated 30, 45, 90, 120, 180, 240 and 360 minutes after dosing. Pain relief was evaluated at the same time points by means of a categorical scale. The time point of first pain relief, the use of rescue medication and the global evaluation of efficacy were also recorded. The reduction in pain intensity was significantly more pronounced in the nimesulide beta cyclodextrin group at 15, 30, 45 and 60 minutes (p&lt;0.01). Pain relief was significantly greater (p&lt;0.05) and more rapid with nimesulide beta cyclodextrin. In the patient overall assessment of efficacy, nimesulide beta cyclodextrin and nimesulide were rated excellent or good by 95% and 92% respectively; only one patient in the nimesulide beta cyclodextrin group needed rescue medication. Both study drugs were effective and well tolerated in the treatment of acute dental pain, with nimesulide beta cyclodextrin showing a faster onset of analgesic action.

Nimesulide versus diclofenac in the treatment of osteoarthritis of the hip or knee: An active controlled equivalence study

The objective of this study was to compare the efficacy and tolerability of nimesulide with those of diclofenac in patients suffering from osteoarthritis of the hip or knee and with moderate-to-severe pain. In this multicenter, double-masked, parallel-group study, 279 outpatients were randomly allocated to receive nimesulide 100 mg twice daily or diclofenac 50 mg three times daily over a 24-week period. The main efficacy assessment was a combined analysis of 7 individual criteria: patient's global evaluation of efficacy, the Lequesne functional index, global pain, nocturnal pain, morning stiffness, inactivity stiffness, and the Doyle articular index. Nimesulide was shown to be as effective as diclofenac in the treatment of osteoarthritis of the hip or knee. No between-group differences were reported for either efficacy or overall tolerability. The percentage of patients reporting gastrointestinal adverse events regardless of causality or patient age was significantly lower ( P = 0.042) with nimesulide (36.3%) compared with diclofenac (47.2%). Results of this study suggest that nimesulide is as effective as diclofenac in the long-term treatment of osteoarthritis; however, nimesulide demonstrated a slightly superior gastric safety profile. This finding may be particularly beneficial to the elderly, who are most at risk for these side effects.

Comparative Efficacy and Safety of Calcium Carbasalate plus Metoclopramide versus Ergotamine Tartrate plus Caffeine in the Treatment of Acute Migraine Attacks

This randomized, double-blind, double-dummy, multicenter, parallel-group study aimed at comparing the efficacy and safety of calcium carbasalate (equivalent to 900 mg aspirin) plus metoclopramide 10 mg (CM) with ergotamine tartrate 1 mg plus caffeine 100 mg (EC) administered in the treatment of 2 acute migraine attacks. A total of 296 patients fulfilling the International Headache Society diagnostic criteria for migraine were enrolled. In total, one or two migraine attacks were treated in 268 and 235 patients, respectively. The primary endpoint for the first treated attack was headache relief, with intensity decreasing from moderate or severe to mild or absent 2 h after drug intake. Usual secondary efficacy endpoints were assessed. A superiority of CM over EC was observed for both treated attacks for the main endpoint: success in 54 versus 36%, p = 0.003 for the first attack and 60 versus 44%, p = 0.02 for the second attack. CM was also significantly superior to EC during the first attack for complete headache relief (20 vs. 8%, p = 0.006), nausea (42 vs. 63%, p = 0.007) and willingness to take the drug again (90 vs. 80%, p = 0.043). The global efficacy evaluation, rated by the investigators, was significantly more favorable to CM for both attacks (p = 0.001 for the first attack and p = 0.02 for the second). The patients’ evaluation was significant for the first attack (p = 0.002). The global incidence of adverse events was 45% higher with EC, though not significant (32 vs. 22%, p = 0.075). They were most often unspecific and mild to moderate in intensity. Gastrointestinal side effects were significantly less frequent with CM than EC (7 vs. 21%, p = 0.001). Thus, CM is more effective and has a better gastrointestinal safety than EC in the acute treatment of migraine attacks.

Double-blind, parallel, randomized pilot study comparing the efficacy and tolerance of cetirizine 10 mg, mequitazine 2 � 5 mg and placebo in the treatment of patients suffering from chronic urticaria: Comparison of suppressive effects on histamine-induced weals and flares

In a double-blind, randomized, parallel-group study, 29 adult patients suffering from chronic urticaria were treated with either cetirizine 10 mg od (n = 10), mequitazine 5 mg bid (n = 10), or placebo (n = 9) for 3 weeks. Three symptoms (weals, erythema, pruritus) were rated according to severity (none, mild, moderate, severe) by the investigator at each of the four visits (days 1, 3, 14, 21). At each visit the investigator and patients also assessed the patients' general condition using a 5-point scoring system (very bad, bad, moderate, good, very good). On day 21 the global evaluation of efficacy and tolerance was assessed by the investigator and patients on a 4-point scale (excellent, good, moderate, bad). Also, a histamine skin-prick test was performed on days 3, 14, and 21. Evaluation of safety was based on the frequency of patients reporting adverse events as well as the clinical laboratory results. The cetirizine, mequitazine, and placebo groups of patients were comparable at inclusion. Overall compliance with the trial schedule was excellent for all groups. After 3 days of treatment a significant improvement in control of all urticaria symptoms was observed in the cetirizine group. Cetirizine elicited a statistically significant better control of pruritus (P = 0.006) and erythema (P = 0.018) than mequitazine on day 21. A trend in favor of cetirizine vs. mequitazine was also observed regarding control of weals (P = 0.114). Cetirizine clearly and rapidly improved the general condition of the patient as evaluated by both patients and investigator compared to the baseline results. The differences vs. mequitazine as well as vs. placebo were statistically significant on every visit, starting from day 3. After three weeks of treatment, the clinical efficacy results in the cetirizine group were rated by both patients and investigator as excellent or good, which was statistically significantly better than the results obtained in the mequitazine and placebo group (P > 0.05). The histamine skin-prick test results revealed a marked difference for the group treated with cetirizine compared to the two other groups in favor of CTZ. On day 3, cetirizine produced a statistically significant suppression of the weals (98%) and flares (74%), compared to 24% and 3%, respectively, by mequitazine. With respect to the tolerance results, no statistically significant differences were observed between the three groups. The safety profile was similar for all groups. No serious adverse event has been reported during the present study, nor did the treatments induce any clinically significant abnormal changes in the laboratory tests. It can be concluded from the present study that the effect of cetirizine was statistically and clinically significantly superior to that of mequitazine. On the other hand, of all parameters studied there were no marked differences between the patients of the mequitazine group and the patients of the placebo group. Drug Dev. Res. 43:185–192, 1998. © 1998 Wiley-Liss, Inc.

Double‐blind, parallel, randomized pilot study comparing the efficacy and tolerance of cetirizine 10 mg, mequitazine 2 × 5 mg and placebo in the treatment of patients suffering from chronic urticaria: Comparison of suppressive effects on histamine‐induced weals and flares

In a double-blind, randomized, parallel-group study, 29 adult patients suffering from chronic urticaria were treated with either cetirizine 10 mg od (n = 10), mequitazine 5 mg bid (n = 10), or placebo (n = 9) for 3 weeks. Three symptoms (weals, erythema, pruritus) were rated according to severity (none, mild, moderate, severe) by the investigator at each of the four visits (days 1, 3, 14, 21). At each visit the investigator and patients also assessed the patients' general condition using a 5-point scoring system (very bad, bad, moderate, good, very good). On day 21 the global evaluation of efficacy and tolerance was assessed by the investigator and patients on a 4-point scale (excellent, good, moderate, bad). Also, a histamine skin-prick test was performed on days 3, 14, and 21. Evaluation of safety was based on the frequency of patients reporting adverse events as well as the clinical laboratory results. The cetirizine, mequitazine, and placebo groups of patients were comparable at inclusion. Overall compliance with the trial schedule was excellent for all groups. After 3 days of treatment a significant improvement in control of all urticaria symptoms was observed in the cetirizine group. Cetirizine elicited a statistically significant better control of pruritus (P = 0.006) and erythema (P = 0.018) than mequitazine on day 21. A trend in favor of cetirizine vs. mequitazine was also observed regarding control of weals (P = 0.114). Cetirizine clearly and rapidly improved the general condition of the patient as evaluated by both patients and investigator compared to the baseline results. The differences vs. mequitazine as well as vs. placebo were statistically significant on every visit, starting from day 3. After three weeks of treatment, the clinical efficacy results in the cetirizine group were rated by both patients and investigator as excellent or good, which was statistically significantly better than the results obtained in the mequitazine and placebo group (P > 0.05). The histamine skin-prick test results revealed a marked difference for the group treated with cetirizine compared to the two other groups in favor of CTZ. On day 3, cetirizine produced a statistically significant suppression of the weals (98%) and flares (74%), compared to 24% and 3%, respectively, by mequitazine. With respect to the tolerance results, no statistically significant differences were observed between the three groups. The safety profile was similar for all groups. No serious adverse event has been reported during the present study, nor did the treatments induce any clinically significant abnormal changes in the laboratory tests. It can be concluded from the present study that the effect of cetirizine was statistically and clinically significantly superior to that of mequitazine. On the other hand, of all parameters studied there were no marked differences between the patients of the mequitazine group and the patients of the placebo group. Drug Dev. Res. 43:185–192, 1998. © 1998 Wiley-Liss, Inc.

Comparative clinical efficacy of shampoos containing ciclopirox olamine (1.5%) or ketoconazole (2%; Nizoral®) for the control of dandruff/seborrhoeic dermatitis

The efficacy and acceptability of ciclopirox olamine (1.5%) and ketoconazole (2%; Nizoral®) shampoos were compared in ‘half-head’ (30 subjects with mild dandruff) and in controlled ‘whole-head’ (163 subjects with moderate to severe dandruff and/or seborrhoeic dermatitis) studies. Shampooing was twice weekly. In both studies, an unmedicated shampoo was used during a 2-3 week run-in period, followed by a 4-week double-blind, randomized treatment period. There was a 2-week unmedicated shampoo follow-up period in the whole-head study. A technician assessed the extent and severity of dandruff, the degree of redness and of scaling due to seborrhoeic dermatitis and the area affected, and made a global efficacy evaluation. Subjects self-assessed dandruff, overall scalp itching, itching of the area affected with seborrhoeic dermatitis and dryness/greasiness of their hair, and gave an overall opinion of treatment. The half-head study showed that both medicated shampoos significantly reduced dandruff and scalp itching at 4 weeks with no differences between treatments. The wholehead study showed that ciclopirox olamine, ketoconazole and the control (unmedicated shampoo base) each improved dandruff and/or seborrhoeic dermatitis significantly with both medicated shampoos being equally effective and also superior to the control shampoo at 4 weeks. Between baseline and day 43, the decrease in dandruff score was significantly greater for ketoconazole than for ciclopirox olamine with the difference between treatments being significant. In both studies, ciclopirox olamine (1.5%) was effective in the treatment of scalp disorders and was as well tolerated as ketoconazole.

Sustained-Release Isosorbide-5-Mononitrate Supports Captopril Treatment of Heart Failure Due to Coronary Artery Disease

A pilot placebo-controlled, double-blind, randomised trial was carried out to ascertain whether patients with cardiac failure due to coronary artery disease would benefit further from an additional application of isosorbide-5-mononitrate (IS-5-MN) along with basic Captopril treatment. 21 patients were randomised in this study. Complete haemodynamic data sets of 11 patients in the placebo group and 7 patients in the IS-5-MN group were available for efficacy evaluation. The main target parameter was the mean pulmonary artery pressure (MPAP) during ergometric exercise. After 28 days of treatment with either IS-5-MN or placebo, patients’ MPAP decreased from 43.3 to 35.6mm Hg with IS-5-MN and from 44.2 to 43.8mm Hg in the placebo group under comparable load. Under resting conditions, there was a similar decrease from 27.4 to 22.4mm Hg in the IS-5-MN group and from 26.4 to 25.3mm Hg in the placebo group. The global evaluation of efficacy was judged by the physician as being good in 7 cases in the IS-5-MN group compared with only 1 patient in the placebo group. Two patients in the IS-5-MN group dropped out because of continuous, nonsevere headaches, which were attributed to the use of the test drug.

Oral Diclofenac Dispersible Provides a Faster Onset of Analgesia than Intramuscular Ketorolac in the Treatment of Postoperative Pain

The objective of this study was to compare the efficacy and tolerability of single doses of a new oral formulation, diclofenac dispersible, with parenteral ketorolac in patients with postoperative pain following orthopaedic surgery. In this double-blind, double-dummy, between-patient study, 55 adult inpatients experiencing moderate-to-severe pain within 2 hours after surgery were randomly allocated to receive diclofenac dispersible 50mg orally or ketorolac 30mg intramuscularly. The primary efficacy variable was pain intensity at 15 minutes. Secondary efficacy variables included pain relief and global evaluation of efficacy by patient and investigator. Diclofenac dispersible was significantly superior to ketorolac with respect to the primary efficacy variable (p = 0.012). The area under the pain intensity-time curve from zero to 6 hours (AUC0–6) for reduction in pain intensity and the peak intensity difference values were also superior for diclofenac, although the differences just failed to reach statistical significance (p = 0.06). Pain relief scores were clinically and numerically superior in diclofenac recipients compared with ketorolac recipients over the 6-hour observation period. AUC0–6 for pain relief was significantly higher for the diclofenac-treated group compared with ketorolac-treated patients (p = 0.0002). Both treatments were well tolerated.

Large scale safety study of ketoprofen 25 mg (Toprec) in febrile and painful conditions.

To assess the safety, tolerability and efficacy of low-dose ketoprofen (75-150 mg daily for 5 to 15 days) in a general practice setting. Open label, non-controlled study of ketoprofen 25 mg tablets in the treatment of pain in ENT diseases, dysmenorrhoea, and musculoskeletal disorders. General practice, 600 investigators Four thousand and sixty-eight patients, aged 13-93 years, mean 42.3 years, 1009 with ENT diseases (mean age 38.8 (13-83) years, 53% female), 978 with dysmenorrhoea (mean age 30.3 (13-60) years, 100% female), 2081 with musculoskeletal disorders (mean age 49.6 (16-93) years, 54% female). Occurrence of adverse events, on patient and physician evaluation; dose and duration of treatment prescribed/taken (diary); global evaluation of efficacy by patient and physician. Twenty-two patients were lost to follow-up (<1%); dose effectively taken was lower than prescribed (3.3 versus 3.6 tablets/day); treatment was stopped prematurely in 3.3% of patients because of adverse events, in 17.1% because of early success of therapy. Gastrointestinal adverse events (AE) were the most frequent (76%) of AE), occurring in 10% of patients. They were more frequent in patients with musculoskeletal pain, who were older and had more associated diseases. Five patients were hospitalized, two for preplanned hospitalizations, the others for one asthma attack, one worsening of low back pain, and one angina attack, none attributed to treatment by the GP. None of the AE was life-threatening. Identified risk factors for AE were age and previous medical history, especially of gastrointestinal disorders. Good quality large scale studies with little or no loss to follow-up can be done in a general practice setting. At the dose used, ketoprofen was generally well tolerated, and used at a lower dose than prescribed, it was not associated with severe or new side-effects. The results of this study could justify its use in self-medication in these indications.

Large Scale Safety Study of Ketoprofen 25 mg (Toprec) in Febrile and Painful Conditions

Objective—To assess the safety, tolerability and efficacy of low-dose ketoprofen (75–150 mg daily for 5 to 15 days) in a general practice setting. Design—Open label, non-controlled study of ketoprofen 25 mg tablets in the treatment of pain in ENT diseases, dysmenorrhoea, and musculoskeletal disorders. Setting—General practice, 600 investigators Subjects—Four thousand and sixty-eight patients, aged 13–93 years, mean 42.3 years, 1009 with ENT diseases (mean age 38.8 (13–83) years, 53% female), 978 with dysmenorrhoea (mean age 30.3 (13–60) years, 100% female), 2081 with musculoskeletal disorders (mean age 49.6 (16–93) years, 54% female). Main outcome measures—Occurrence of adverse events, on patient and physician evaluation; dose and duration of treatment prescribed/taken (diary); global evaluation of efficacy by patient and physician. Result—Twenty-two patients were lost to follow-up (<1%); dose effectively taken was lower than prescribed (3.3 versus 3.6 tablets/day); treatment was stopped prematurely in 3.3% of patients because of adverse events, in 17.1% because of early success of therapy. Gastrointestinal adverse events (AE) were the most frequent (76%) of AE), occurring in 10% of patients. They were more frequent in patients with musculoskeletal pain, who were older and had more associated diseases. Five patients were hospitalized, two for preplanned hospitalizations, the others for one asthma attack, one worsening of low back pain, and one angina attack, none attributed to treatment by the GP. None of the AE was life-threatening. Identified risk factors for AE were age and previous medical history, especially of gastrointestinal disorders. Conclusions—Good quality large scale studies with little or no loss to follow-up can be done in a general practice setting. At the dose used, ketoprofen was generally well tolerated, and used at a lower dose than prescribed, it was not associated with severe or new side-effects. The results of this study could justify its use in self-medication in these indications.

Comparison of the Efficacy of Isosorbide Dinitrate Spray and Nitroglycerin Spray in the Regression of Symptoms of Exercise-Induced Moderate Angina Pectoris

This single-centre, controlled, randomised, double-blind, crossover trial was carried out to evaluate the time to recovery from angina pectoris after application of an isosorbide dinitrate (ISDN) spray formulation, which was developed a few years ago (Isoket® spray, Schwarz Pharma, Monheim, Germany), in comparison with that with nitroglycerin (NG) spray in patients with chronic stable angina with documented coronary artery disease. A secondary objective of this trial was to evaluate the safety and tolerability of ISDN spray. 65 patients were randomised to this study; 62 patients were evaluated for efficacy in the intent-to-treat analysis and 28 patients could be evaluated for the per-protocol analysis. Considering the pooled data of the intent-to-treat analysis, patients receiving ISDN spray (2 squirts of 1.25mg ISDN each) recovered after 67.16 seconds, compared with patients administered NG spray treatment (2 squirts of 0.4mg NG each) who recovered after 74.11 seconds (mean difference 6.95 seconds). The Moses 90% confidence interval clearly indicated that the two treatments were equivalent with regard to the clinically relevant difference of 30 seconds as defined in the protocol. In the per-protocol analysis, the pooled data demonstrated that the mean time to recovery from angina pectoris was 63.86 seconds in the ISDN spray-treated patients compared with 71.14 seconds in the NG spray-treated patients. This analysis also indicated that the treatments were equivalent with regard to the clinically relevant difference of 30 seconds as defined in the protocol (Moses 90% confidence interval). In the intent-to-treat analysis the global evaluation of efficacy showed that the investigator rated ISDN spray to be ‘very good’ or ‘good’ in 55 cases and NG spray to be ‘very good’ or ‘good’ in 54 cases. In 56 cases in the ISDN spray group and in 55 cases in the NG spray group treatment was classified as ‘very good’ or ‘good’ by the patients. Comparable results were obtained in the per-protocol analysis. Four adverse events were reported: 2 cases of orthostatic hypotension occurred during the nitrate response test, and 2 patients developed ventricular arrhythmia. In all cases the investigators denied any relationship to the study medication.

Placebo-controlled, double-blind study of the efficacy and safety of triamcinolone acetonide aerosol nasal inhaler in pediatric patients with seasonal allergic rhinitis

Triamcinolone acetonide (TAA) aerosol nasal inhaler has been shown to effectively relieve the symptoms of seasonal allergic rhinitis in adults and adolescents. We conducted a study to evaluate the efficacy and safety of once-daily administration of TAA aerosol nasal inhaler in pediatric patients aged 6 to 11 years with grass seasonal allergic rhinitis. This multicenter, randomized, double-blind, placebo-controlled, parallel-group study enrolled 116 children who were treated with either TAA aerosol nasal inhaler (220 μg/d) or placebo once daily for 2 weeks. Patients evaluated the severity of rhinitis symptoms (nasal stuffiness, discharge, sneezing, and itching) daily according to a four-point scale (0 = absent, 1 = mild, 2 = moderate, and 3 = severe). Patients' and physicians' global evaluations of overall treatment efficacy were assessed at the end of the 2-week treatment period. Patients treated with TAA aerosol nasal inhaler had significantly greater reductions in all nasal symptom scores overall and in virtually all symptoms at the end of week 1 and week 2 compared with those in the placebo group. Both patients' and physicians' global evaluations of efficacy favored TAA aerosol nasal inhaler over placebo. This study demonstrated that once-daily administration of 220 μg of TAA aerosol nasal inhaler was well tolerated and effectively reduced the symptoms of seasonal allergic rhinitis in pediatric patients.

Triamcinolone acetonide aqueous nasal spray in patients with seasonal ragweed allergic rhinitis: A placebo-controlled, double-blind study

Because some patients may prefer aqueous nasal sprays and once-daily dosing for relief of seasonal allergic rhinitis symptoms, a new aqueous formulation of triamcinolone acetonide (TAA Aqueous) was developed. We conducted a randomized, placebo-controlled, double-blind study to compare the efficacy and safety of once-daily administration of 220 μg/d of TAA Aqueous for 1 week, followed by either 220 μg/d or 110 μg/d for an additional 2 weeks, with that of placebo in 429 patients with seasonal allergic rhinitis. Patients recorded the severity of symptoms (nasal stuffiness, discharge, sneezing, nasal index [the sum of the first three variables], nasal itching, and eye symptoms) on daily diary cards. Patients' and physicians' global evaluations of efficacy were made at the end of the 3-week study period. Both regimens of TAA Aqueous significantly improved symptoms compared with placebo at most time points. Patients demonstrated significant improvements in nasal symptoms as early as the first day of treatment (within 12 to 16 hours based on treatment in the morning and symptom assessment at bedtime). Although TAA Aqueous 220 μg/d provided numerically greater reductions in nasal symptoms compared with 110 μg/d, these differences in efficacy over the last 2 weeks were not statistically significant. The incidence of adverse effects with both TAA Aqueous regimens was low and comparable to that of placebo. In summary, during the first week of therapy, TAA Aqueous 220 μg/d significantly reduced nasal symptoms. During the last 2 weeks of therapy, the 110 μg/d regimen of TAA Aqueous was effective as continued therapy for most patients. Both the 110 μg/d and 220 μg/d regimens of TAA Aqueous provided significantly better relief of nasal symptoms than did placebo.

Chronic Administration of Zopiclone and Nitrazepam in the Treatment of Insomnia

The hypnotic effects of 7.5 mg zopiclone, as well as its unwanted and residual effects, were compared with those of 5 mg nitrazepam in a double-blind, randomized, multicenter, parallel group study. After an initial, 7-day, placebo wash-out period, insomniac out-patients under the care of general practitioners received either 7.5 mg zopiclone or 5 mg nitrazepam for 6 weeks. Everyday, the patients filled in a diary (analogue scales for sleep parameters and condition during daytime); a sleep questionnaire was filled in at baseline and at the end of active treatment period; every 2 weeks, a somatic complaint check-list inventory and a mood rating scale were filled in and psychomotor tests performed; and at the end of the study, a global evaluation of efficacy and acceptability was given by the investigator. Clinical laboratory tests were performed before and after the active treatment period. From the diary, sleep onset latency, as well as sleep quality, were similarly improved by both drugs throughout the whole study. From the sleep questionnaire, all sleep parameters measured were improved at the end of the 6-week treatment period in both groups. No statistical differences in the various psychomotor tests were observed between the two treatment groups, and a significant improvement in the working ability of patients was noted with both drugs. Some significant differences were observed in the mood rating scale and the somatic complaint check list, probably related to differences in pharmacokinetics of the two drugs.

Comparative study of flurbiprofen and morphine for postsurgical gynecologic pain

This single-dose, double-blind, randomized, placebo-controlled study assessed the efficacy and safety of 50 mg of flurbiprofen (Ansaid, Upjohn) in the relief of postoperative pain following cesarean section, at well as vaginal or abdominal hysterectomies. Results show that both 50 mg of oral flurbiprofen and 10 mg of intramuscular morphine sulfate were Significantly superior to placebo in 161 patients with respect to pain intensity after medication, pain relief scores, need for additional analgesia, and overall clinical evaluation of pain relief. By two hours after treatment, there were no significant differences between morphine sulfate and flurbiprofen in terms of pain intensity or degree of pain relief. According to investigators' global evaluations of efficacy, both active treatments were statistically superior to placebo. The only adverse reaction occurred in the morphine treatment group. Flurbiprofen administered orally for the relief of moderate to severe pain following major gynecologic surgery appears to be equal to morphine sulfate and superior to placebo in efficacy arid safety. Unlike morphine, flurbiprofen is a non-parenteral, uncontrolled substance, and thus patient acceptance is improved while nursing time is decreased.