Otilonium bromide in irritable bowel syndrome: a double-blind, placebo-controlled, 15-week study.

AIM: To evaluate the efficacy of otilonium bromide, a spasmolytic agent, in the treatment of irritable bowel syndrome using modern and validated diagnostic criteria. METHODS: Three hundred and seventy-eight patients with irritable bowel syndrome were enrolled in the study. At entry, endoscopy/barium enema, clinical examination and laboratory tests were used to rule out organic diseases. After a 2-week placebo run-in, 325 patients were randomly assigned to receive either otilonium bromide 40 mg t.d.s. or placebo for 15 weeks. Abdominal pain, abdominal distension and disturbed defecation were scored at the beginning of the study and every 5 weeks. A global determination of well-being by visual analogue scale and the tenderness of the sigmoid colon were also scored. RESULTS: The reduction in the number of abdominal pain episodes was significantly higher (P < 0.01) in otilonium bromide patients (55.3%) than in those taking placebo (39.9%) as was the severity of abdominal distension (42.0%, vs. 30.2%; P < 0.05). Bowel disturbance improved in both groups. but without any statistically significant difference. The visual analogue scale of well-being revealed a significant improvement (P < 0.05) in patients taking otilonium bromide. The investigators' global positive assessment was in favour of otilonium bromide (65.2%) compared with placebo (49.6%) (P < 0.01). CONCLUSIONS: Otilonium bromide may represent an effective treatment for irritable bowel syndrome because it reduces its predominant symptom (abdominal pain/ discomfort) more than placebo does.

Fenoverine: smooth muscle synchronizer for the management of gastro-intestinal conditions. II. A trimebutine-controlled, double-blind, crossover clinical evaluation.

A double-blind, crossover trial was carried out in 40 in-patients with gastro-intestinal spasmodic syndromes to compare the effectiveness and tolerance of fenoverine and trimebutine. Patients were allocated at random to receive either 100 mg fenoverine or 150 mg trimebutine 3-times daily for 20 days and were then crossed over, without a wash-out period, to the alternative medication for a further 20 days. After the first dose, pain severity was monitored over 4 hours and changes in intensity compared between groups. During the two 20-day periods, the proportion of patients in complete or almost complete remission was monitored at 10-day intervals, and the pooled data similarly compared. At the end of the 40-day trial period, patients stated their preference for one or other treatment, and the relevant data were processed by sequential analysis. Subjective signs of adverse effects were monitored by questioning every 10 days, and haematology and haematochemistry before and after each phase of the study. The results showed that fenoverine produced significantly greater pain relief after a single dose in comparison with trimebutine over the 4 hours of observation. Similarly, it gave significantly more favourable clinical results after both the 10th and 20th day of treatment. Finally, according to the patients' preference, fenoverine was significantly preferred (p less than 0.05) in comparison with trimebutine. Neither treatment was associated with the onset of signs of possible adverse reactions, either subjective or objective.

Double-blind preference and compliance multicentre study in osteoarthritis: once-a-day treatment.

Two-hundred-and-three female patients (mean age: 58 yrs; SD: 8.2 yrs) suffering from osteoarthritis entered this late phase IV multicentre, stratified according to previous therapy (e.g. ketoprofen, naproxen, aspirin, indomethacin or indoprofen), randomized, double-blind, between within-patient trial of 2-week duration. Each patient received either diclofenac SR 100 mg/day (D), piroxicam 20 mg/day (P), or placebo (P1 by oral route. Clinical evaluation (functional class; pain assessment; osteoarthritic condition; joint motility and stiffness) was performed at entry, as well as after the first and the second week. Patient compliance and reported signs and symptoms were recorded after the first week and at the end of the trial. Patient preference, as regards previous therapy, and global evaluation (both by the physicians and the patients) were checked at the end of the trial. The clinical evaluation showed a superiority of D and P over P1. No difference was seen between the two active drugs. Placebo effect was very strong. Global evaluation was significantly in favour of D and P. Patient compliance was extremely good (greater than or equal to 95%). Diclofenac was preferred to naproxen, aspirin and indomethacin, while piroxicam and placebo were preferred only to aspirin. The tolerability of the two active drugs was good and comparable. A significantly lower number of patients complaining of unwanted effects (u.e.) was detected in the placebo group. The number of patients withdrawn for u.e. was similar in the three trial groups.

Nizatidine in the short-term treatment of duodenal ulcer--an Italian Multicenter Study.

One hundred and seventy three patients suffering from duodenal ulcer, were selected for a double-blind, controlled and randomized parallel multicenter study, with interval endoscopic examinations. This study was undertaken to compare the efficacy and safety of nizatidine administered at a single dose (300 mg "nocte") versus ranitidine (300 mg "nocte") in the treatment of acute duodenal ulcer. One hundred and sixty five patients were found to meet every admission criterion and completed the study (86 on nizatidine and 79 on ranitidine). On admission to the study, both groups were seen to have been correctly selected and epidemiologically well-distributed as to history of duodenal ulcer, previous treatments and pre-study symptoms. The ulcer was considered healed when complete re-epithelialization had occurred in areas of ulcerated mucosa. Healing rates of duodenal ulcer proved to be globally similar in the two groups, both in the 4th week (nizatidine, 78%; ranitidine, 78%) and in the 8th week (nizatidine, 91%; ranitidine, 95%). After four weeks of treatment, 67% of the patients treated with nizatidine no longer had any symptoms, while 87% patients no longer suffered from day pain, and 91% had no nocturnal pain. As a result, intake of antacids quickly decreased during the first four weeks. A similar response was observed in the group receiving ranitidine. After administration at a single dose of 300 mg in the evening, nizatidine proved to be at least as effective and safe as 300 mg of ranitidine administered in the same way, with respect both to ulcer healing and symptom response.

Short-term treatment of reflux oesophagitis with ranitidine 300 mg nocte. Italian multicentre study.

A multicentre study involving 9 Italian institutions was carried out to compare the efficacy and safety of ranitidine 150 mg b.i.d. and ranitidine 300 mg nocte in the treatment of reflux oesophagitis. 117 patients with histologically proven oesophagitis were randomly allocated to two comparable treatment groups. Efficacy and reliability were evaluated by clinical and laboratory tests at the beginning of the study, and at 3 and 6 weeks; endoscopy and biopsies were performed at the beginning and at 6 weeks. Treatment with ranitidine for 6 weeks led to total disappearance of gastro-oesophageal reflux symptoms in 60% of patients, with percentages of partial improvement varying between 85% and 95% of cases. Improvement in the results of endoscopic examination was 85%, of which 55% were cured. Microscopic examination revealed an improvement of 36% and 44%, with a cure rate of 18% and 26% respectively. With regard neither to the regression of symptoms nor to the macroscopic and microscopic inflammation of the oesophageal mucosa did statistical examination show significant differences in the therapeutic efficacy of ranitidine 150 mg b.i.d. or 300 mg nocte for treatment of reflux oesophagitis.

Effects of a synthetic prostanoid, rosaprostol, on the changes of gastric acidity and digestive disorders induced by NSAID.

In 24 subjects without upper gastrointestinal lesions, gastric pH was measured from 30 min before until 90 min after the administration of diclofenac sodium (50 mg), piroxicam (20 mg), or 500 mg acetylsalicylic acid. In all these cases a drop of gastric pH was recorded, which started with all the drugs 15 min after their administration and lasted throughout the recording. Pre-treatment with rosaprostol (2 g given 30 min before the start of the trial) prevented the drop in pH. Twenty subjects with chronic joint diseases were divided into two groups in a cross-over double-blind randomized experimental design. One group received piroxicam (20 mg) + rosaprostol (2 g) daily; the other group was treated with piroxicam 20 mg + placebo. The patients were clinically reviewed every week in a month and questioned about their symptoms. Statistical analysis demonstrated that patients with articular diseases treated with NSAIDs + rosaprostol exhibited a frequency and severity of symptoms lower than those recorded in subjects receiving NSAIDs + placebo. Rosaprostol was found to be capable of antagonizing the variations of gastric acid output induced by the oral administration of NSAIDs, and to prevent and treat the occurrence of digestive disorders when given in combination with NSAIDs. These effects result from the action of rosaprostol on the mucosal barrier, and this cytoprotective action is confirmed by the present study with continuous measurements of gastric pH.

[Results and prospects of therapy of type IV dyslipidemia with chenic acid]. / Risultati e prospettive nella terapia della dislipidemia tipo IV con acido chenico.

Administration of 500 mg/day chenodeoxycholic acid for 60 days in a series of 44 patients with type IV dyslipidaemia led to gradual normalisation of triglycerides by the end of the treatment. Falls were greater in subjects with initially higher values, but were independent of age, sex, weight and type of diet. Further falls were obtained by repeating the treatment in some cases when prebetalipoproteins rose again. Decreases were already evident by the 5th day (about 24%) and could be obtained with only 4 mg/Kg/day. The rapid effect of the acid and its specific action on prebetalipoproteins were demonstrated by examination of lipid curves after a glyco-lipid load with and without pretreatment with chenic acid. Encouragement of the shunt of triacylglycerols towards the phosphoglycerides during hepatic synthesis of triglycerides is put forward as the most likely mechanism of action in endogenous hyper-triglyceridaemia. The chemical composition of bile is interfered with, which may explain why cholesterol lithiasis is significantly more common in type IV dyslipidaemia than in other forms and in controls, as shown by statistical analysis.

The association of ranitidine and sucralfate in the short-term treatment of duodenal ulcers, as compared to other forms of treatment.

Results of the treatment of duodenal ulcer with ranitidine (150 mg X 2/die) and sucralfate (1 gr X 2/die) have been compared with other common schemes of therapy. Administration of the drugs was carried out for 8 weeks, and the evolution of the ulcer lesion was followed with endoscopic controls at the beginning and end of the treatment. Ulcer healing occurred in 92% of 25 patients, as compared with 83,3% of 30 cases treated with ranitidine only; 80% of 30 cases with cimetidine 1 g/day; 80% of 20 cases with cimetidine 800 mg/b.i.d.; 75% of 20 cases with sucralfate 3 g/day; 73,3% of 30 patients with pirenzepine 150 mg/day; 60% of 20 cases with sulglycotide 0.5-1 g/day; and 50% of 40 ulcerous patients treated with placebo. From these results it is concluded that the association of sucralfate with an H2-antagonist improves the possibility of short-term healing of duodenal ulcer.

Comparison of once-daily bedtime administration of famotidine and ranitidine in the short-term treatment of duodenal ulcer. A multicenter, double-blind, controlled study.

A multicenter, double-blind, randomized, controlled study was conducted in 234 duodenal ulcer patients to compare the efficacy and safety of the H2-receptor antagonists famotidine and ranitidine in the treatment of duodenal ulcer. Patients received 40 mg famotidine (119 patients) or 300 mg ranitidine (115 patients) once daily at bedtime for 4 weeks. If ulcer lesions persisted, treatment was extended to 6 weeks. Efficacy was assessed by relief of symptoms and endoscopic findings of ulcer healing. Safety was determined on the basis of reports of side effects, results of laboratory tests, and, in selected patients, changes in plasma levels of hormones. The 4- and 6-week healing rates achieved with famotidine were 76% and 91%, respectively, and with ranitidine they were 76% and 87%, respectively; the differences in healing rates for the two drugs were not statistically significant. Similarly, both drugs provided satisfactory relief of pain and dyspeptic symptoms. However, famotidine produced significantly (P less than 0.05) greater relief of postprandial fullness and heartburn. The incidence of untoward effects was low in both treatment groups, and abnormal results in laboratory tests were observed in only one patient, a chronic alcoholic receiving famotidine, who withdrew from the study because of a slight elevation in serum transaminase levels. One patient in the ranitidine treatment group dropped out of the study because of a generalized urticarial rash; however, a causal relationship between drug and effect could not be established. The authors conclude that famotidine may be regarded as the best alternative to ranitidine in the treatment of duodenal ulcer.