Pantoprazole versus omeprazole in the treatment of acute gastric ulcers.

BACKGROUND: Pantoprazole is a new substituted benzimidazole which is a potent inhibitor of gastric acid secretion by its action upon H+,K(+)-ATPase. METHODS: The proton pump inhibitors pantoprazole and omeprazole were compared in a randomized, double-blind study in 219 patients with benign gastric ulcers. Patients received either pantoprazole 40 mg (n = 146) or omeprazole 20 mg (n = 73), once daily before breakfast for 4 weeks. Treatment was extended for a further 4 weeks if the ulcer had not healed. RESULTS: After 4 weeks, complete ulcer healing was seen in 88% of protocol-correct patients given pantoprazole and in 77% given omeprazole (between-group difference P < 0.05). At 8 weeks, the corresponding values were 97% and 96% (not significant). In the comparative intention-to-treat analysis there were no statistical differences between the treatment groups. Among the patients who had ulcer pain prior to treatment, 79% of the pantoprazole group and 68% of the omeprazole group were pain-free after 2 weeks, and after 4 weeks 88% and 81%, respectively (not significant). Pronounced improvement in the other gastrointestinal symptoms was seen in both groups. Only 10% of patients in each group reported adverse events. There were moderate increases in fasting serum gastrin levels with both treatments at 4 and 8 weeks. CONCLUSION: Pantoprazole, 40 mg once daily in the morning, is a highly effective, well tolerated treatment for acute, benign gastric ulcer. Pantoprazole and omeprazole were equally safe in the therapy of gastric ulcer.

Effect of cisapride on relapse of esophagitis. A multinational, placebo-controlled trial in patients healed with an antisecretory drug. The Italian Eurocis Trialists.

The effect of a prokinetic agent, cisapride, on the relapse of reflux esophagitis was investigated in a randomized, double-blind trial conducted in 443 patients whose esophagitis had previously been healed with an acid antisecretory drug. Patients received cisapride, 20 mg at night, cisapride 10 mg twice daily, or placebo for 12 months or until endoscopic relapse was confirmed endoscopically. In 88% of all patients (respectively 133, 132, and 124), endoscopic data were available at discontinuation of treatment. In comparison with placebo, the two cisapride regimens prolonged both the time to endoscopically confirmed relapse (Kaplan-Meier analysis; P = 0.001) and the time to symptomatic relapse (P = 0.012). The life-table endoscopic relapse rates at 12 months were 51% for placebo, 32% for cisapride 20 mg at night (P = 0.005), and 34% for cisapride 10 mg twice daily (P = 0.02). Patients with more severe esophagitis before healing relapsed more rapidly during maintenance therapy, regardless of the treatment regimen. Adverse events were infrequent in all three groups. These findings indicate that maintenance treatment with the prokinetic drug cisapride prevents the relapse of esophagitis after it has been healed by acid antisecretory therapy.

Prokinetic drug treatment (cisapride) is as effective as H2-blocking agent (ranitidine) in the treatment of gastric ulcer.

A double-blind, randomized, parallel-group multicenter study was conducted in 120 patients with gastric ulcer to compare cisapride, 10 mg t.i.d., and ranitidine, 150 mg b.i.d., administered over 8 weeks. No significant differences between the results of the two treatments were found in terms of ulcer healing or symptomatic relief. Endoscopy showed that the incidence of medium-sized or large ulcers was reduced from 85% at the start to 11% and 4%, respectively, after 4 and 8 weeks in the ranitidine group, and from 98% to 15% and 4%, respectively, in the cisapride group. By week 8, the ulcer was healed in 89% of the ranitidine patients, and in 86% of the cisapride patients. Moderate to severe diurnal epigastric pain--the predominant symptom--was reported by about 80% of the patients in week 8, and by less than 15% from week 4 on. The response to nocturnal epigastric pain, epigastric pressure, sensation of fullness and other symptoms was similar. Except for gastrointestinal symptoms in the cisapride patients--nearly always indicative of enhanced bowel contractions--the occurrence of adverse effects was similar in the two groups. The improvement in gastrointestinal motility under cisapride, would appear to be as effective as suppression of acid secretion in the treatment of gastric ulcer disease.

Sucralfate in the treatment and prevention of gastric ulcer: multicentre double blind placebo controlled study.

A randomised controlled multicentre trial was performed in 160 patients with gastric ulcer, proved by endoscopy and biopsy, to compare ulcer healing with sucralfate and ranitidine (double blind double dummy design) and to assess the effect of maintenance treatment with sucralfate on ulcer recurrence (double blind placebo controlled design). The healing rates were similar with 4 g sucralfate suspension per day and 300 mg ranitidine per day (82% and 88% after 12 weeks, respectively). Of the 109 patients with healed ulcers, 92 were entered into the maintenance trial and treated with sucralfate tablets (2 g per day) or placebo tablets. Maintenance treatment with sucralfate delayed symptoms of gastric ulcer recurrence. Lifetable analysis showed significant differences between sucralfate and placebo, both after six months (p = 0.018) and after 12 months (p = 0.044). The rates of symptom recurrences were 13% and 34% after six months and 34% and 55% after 12 months for sucralfate and placebo, respectively. The rate of asymptomatic recurrences after 12 months was similar in the two groups (9% and 10%, respectively). The recurrence rate was higher in patients who had never taken non-steroidal anti-inflammatory drugs than in those who had but had stopped on admission to the study. It was also higher in patients with recurrent ulcer and in those with scarring deformation and narrowing of the pylorus. Maintenance treatment with sucralfate slowed the appearance of symptom recurrences of gastric ulcer.

[Dose finding study of telenzepine (1.5 vs. 3 vs 5 mg once daily) in acute treatment of duodenal ulcer. A double-blind, randomized, multicenter parallel group comparison]. / Dosisfindungsstudie von Telenzepin (1.5 vs. 3 vs. 5 mg, einmal täglich) in der Akuttherapie des Ulcus duodeni. Ein doppelblinder, randomisierter, multizentrischer Parallelgruppenvergleich.

Three different doses of the M1-selective antimuscarinic compound telenzepine were investigated in the treatment of acute duodenal ulcer in a randomized, double-blind dose-range finding study. In four investigating centers, 120 patients with endoscopically proven, florid duodenal ulcer were treated with either 1.5 mg, 3 mg or 5 mg telenzepine once daily at bedtime (40 patients per dose group). After two weeks of treatment differences in the healing rates were statistically not significant. After four weeks the ulcers of 26 (65%) patients in the 1.5 mg group and 34 (85%) and 31 (78%) in the 3 mg and 5 mg groups, respectively, were completely healed. Only the difference in the healing rates between the 1.5 and 3 mg groups was significant at p less than 0.05. Mean reductions in ulcer area were 90% (1.5 mg), 97% (3 mg) and 93% (5 mg) after four weeks; 1.5 vs. 3 mg, p less than 0.025. These results show that telenzepine dose-dependently accelerates ulcer healing and that maximal effect is obtained with the 3-mg dose. The ulcer symptoms were dose-dependently alleviated. Dry mouth of moderate or severe intensity was stated more frequently under 5 mg telenzepine (by 14% of patients) than under 1.5 and 3 mg (5% each). The antimuscarinic side effect "disturbed accommodation" was rarely found. It is concluded that once daily administration of 3 mg in the evening must be regarded as the optimal dosage regimen of telenzepine.

Cisapride versus ranitidine in the treatment of reflux esophagitis.

The healing effect of the prokinetic drug cisapride (10 mg q.i.d.) on esophageal lesions, and its therapeutic control of gastroesophageal reflux symptoms were compared with the effects of the H2-antagonist ranitidine (150 mg b.i.d. + placebo b.i.d.) in a double-blind trial. In each group, 28 patients with Savary-Miller Grade I or II esophagitis were treated for 6 or 12 weeks. At the end of treatment, follow-up endoscopy showed that mucosal lesions were absent in 89% of the cisapride patients and in 79% of the ranitidine patients. In addition, 86% and 82% of the patients in the cisapride and the ranitidine group, respectively, had no, or only mild, reflux symptoms. Minor side effects were experienced in both groups. From these data, cisapride appears to be as effective as ranitidine in controlling reflux symptoms and in promoting the healing of mucosal lesions in milder forms of reflux esophagitis.

Early evening ranitidine administration promotes faster duodenal ulcer healing.

In a prospective double-blind clinical trial, 141 patients with endoscopically diagnosed duodenal ulcer were randomly assigned to treatment with ranitidine 300 mg, taken either at 6 PM or at 10 PM. After 2 wk of treatment, 52 of 70 patients (74%) in the 6 PM treatment group had healed, compared with 32 of 64 patients (50%) taking ranitidine at 10 PM (p less than 0.01). After 4 wk, the cumulative healing rates were 100% and 94%, respectively, for the 6 PM and 10 PM treatment regimens. These results suggest that ranitidine, taken as a single daily 300-mg dose at 6 PM after dinner, provides more rapid duodenal ulcer healing than the same dose of the drug taken at 10 PM.

A comparison of roxatidine acetate and ranitidine in duodenal ulcer healing.

A randomised double-blind study was conducted to compare the efficacy of roxatidine acetate 75 mg twice daily with ranitidine 150 mg twice daily in 308 patients with endoscopically confirmed uncomplicated duodenal ulcers. After 6 weeks of treatment ulcer healing was found in 93.5% of the roxatidine acetate group and 89.2% of the ranitidine group, with no significant differences between treatment groups. The relief of day and night-time epigastric pain assessed at clinic visits or on diary cards by patients was comparable for both treatment groups, as was the consumption of antacid tablets for relief of symptoms of dyspepsia. There were no significant differences in the healing rates of smokers and non-smokers for either roxatidine acetate or ranitidine treatment, and no clinically significant alterations in laboratory values. Eight patients in the roxatidine acetate group and 1 in the ranitidine group complained of mild side effects, which included diarrhoea, constipation and headache. One patient on roxatidine acetate withdrew from treatment because of a mild skin rash. The results confirm that roxatidine acetate is a safe and effective treatment for duodenal ulcer disease.

[Therapy of stomach ulcer with sucralfate and ranitidine. A multicenter double-blind study]. / Therapie des Ulcus ventriculi mit Sucralfat und Ranitidin. Eine multizentrische Doppelblindstudie.

134 outpatients with acute benign gastric ulcer confirmed by endoscopic biopsy received either 1 g sucralfate suspension four times daily or one 150 mg ranitidine tablet twice daily for six to 12 weeks in a multicentre therapy study (double-blind study according to the double-dummy technique). After six to 12 weeks, respectively, 56% and 82% of the ulcers had healed in the sucralfate group. The rates of healing in the ranitidine group were 72% and 88%, respectively. The differences in the rates of healing between sucralfate and ranitidine were not statistically significant. Ranitidine was superior to the sucralfate suspension in corpus ulcer. In the distally located ulcers, the two kinds of treatment were equivalent. There were no appreciable differences between the medications with regard to antacid consumption and compliance. Gastric pain was influenced better by ranitidine than by sucralfate.

Comparative clinical trial of enprostil and ranitidine in the treatment of gastric ulcer.

In a randomized, double-bind, parallel, multi-clinic study, the safety and efficacy of enprostil (35 micrograms twice daily) and ranitidine (150 mg twice daily) were compared in the treatment of active gastric ulcer in 93 outpatients (47 enprostil-treated patients and 46 ranitidine). The two treatment groups were well matched for demographic characteristics. The healing rates in the enprostil group were 22, 58, 80, and 86 percent at two, four, six, and eight weeks, respectively. The corresponding rates in the ranitidine group were 22, 66, 84, and 89 percent. None of these differences was statistically significant. The area of the ulcer at baseline and smoking status did not appear to influence healing rates. There were no significant differences between treatment groups in time to relief of ulcer symptoms, frequency of daytime or nighttime ulcer pain, or antacid use. Side effects attributable to enprostil treatment were diarrhea (10 percent versus 6 percent with ranitidine), gastrointestinal pain, and vomiting. These side effects, however, did not influence the patients' assessments of their overall response to enprostil and ranitidine therapy. Six enprostil-treated patients and one ranitidine-treated patient withdrew from the trial prematurely because of adverse experiences. Monitoring of clinical laboratory test results showed no significant changes in the two treatment groups. This study demonstrates that a prostaglandin E2 analogue, enprostil, in a dose of 35 micrograms twice daily, is similarly safe and effective as ranitidine in the treatment of active gastric ulcer.

[Stomach ulcer healing with enprostil, an orally effective prostaglandin E2 analog: direct comparative study with ranitidine]. / Ulcus-ventriculi-Abheilung unter Enprostil, einem oral wirksamen Prostaglandin-E2-Analog: Eine direkte Vergleichsstudie mit Ranitidin.

In a randomized, endoscopically controlled double-blind trial the effectiveness of a twice daily dose of the prostaglandin E2-analogue enprostil was compared with ranitidine given to 93 ambulatory patients with benign gastric ulcers. Under 35 micrograms b.i.d. enprostil the ulcer healing rates after 2, 4, 6 and 8 weeks averaged 22% (10/46), 58% (26/45), 80% (35/44) and 86% (37/43). The corresponding values for ranitidine 150 mg b.i.d. were 22% (10/46), 66% (29/44), 84% (38/45) and 89% (41/46). The differences were not statistically significant. Both drugs had a similar influence on the ulcer symptoms and were well tolerated. The findings suggest that enprostil can be given in a twice daily dosage in the treatment of benign gastric ulcers.

20 versus 30 mg omeprazole once daily: effect on healing rates in 115 duodenal ulcer patients.

In a double-blind, dose comparison multicenter trial 115 patients with duodenal ulcer were treated with either 20 or 30 mg oral omeprazole once daily for 4 weeks. There was no difference in the healing rates for the two groups after 2 and 4 weeks. After 2 weeks with 20 and 30 mg healing frequencies were 79.0 and 72.7%, after 4 weeks 96.5 and 92.7%. No difference was observed between the groups in the number of pain episodes during day and night. No side effects to the drug occurred. A daily dose of 20 mg omeprazole may be effective in ulcer therapy.

Omeprazole heals duodenal, but not gastric ulcers more rapidly than ranitidine. Results of two German multicentre trials.

In two double-blind, randomized German multicentre trials the effects of omeprazole 20 mg mane and ranitidine 150 mg b.i.d. were compared for the first time in 334 outpatients with duodenal ulcer and 184 outpatients with gastric ulcer. In patients with duodenal ulcer endoscopically controlled healing rates after two weeks were 72% with omeprazole and 59% with ranitidine (p = 0.012); after 4 weeks 96 and 92%, resp. were healed (n.s.). In patients with gastric ulcer the healing rates after two, four, and eight weeks were 43, 81, and 95%, respectively, with omeprazole and 45, 80, and 90%, respectively, with ranitidine (n.s.). Smoking impaired healing in duodenal, but not in gastric ulcer. Symptom relief was comparable with both drugs. Serious side effects or clinically relevant changes in laboratory screening results were not detected. - Our results demonstrate for the first time that omeprazole 20 mg mane is superior to ranitidine 150 mg b.i.d. in the short-term treatment of duodenal, but not gastric ulcer.

[Healing rates following omeprazole and ranitidine treatment of gastric ulcer. Results of a German multicenter study]. / Abheilungsraten nach Omeprazol- und Ranitidin-Behandlung des Ulcus ventriculi. Ergebnisse einer deutschen Multizenterstudie.

The effectiveness of omeprazole (20 mg orally each morning) or ranitidine (150 mg orally twice daily) in the treatment of gastric ulcer was compared in 184 out-patient in a randomized, endoscopically controlled multi-centre double-blind ("double dummy") trial. Healing rates with omeprazole after two, four and eight weeks were 43, 81 and 95%, respectively, those with ranitidine were 45, 80 and 90%, a statistically not significant difference. Independently of medication, small ulcers (less than 8 mm diameter) healed more quickly than larger ones. Ulcers in the body of the stomach responded poorest to both drugs. Smoking had no statistically significant effect on healing rate. Omeprazole and ranitidine had similarly favourable effects on symptoms. Neither side effects nor changes in biochemical parameters could be ascribed to omeprazole. Both drugs had equivalent effects on the healing of gastric ulcers in the stated dosages.

[Short-term therapy of duodenal ulcer with omeprazole and ranitidine. Results of a German multicenter study]. / Kurzzeit-Therapie des Ulcus duodeni mit Omeprazol und Ranitidin. Ergebnisse einer deutschen Multizenterstudie.

In a randomized, endoscopically controlled double-blind trial the effectiveness of a single oral, morning dose of 40 mg omeprazole was compared with a twice daily oral dose of 150 mg ranitidine given to 334 ambulatory patients with duodenal ulcers. Under omeprazole 105 of 146 duodenal ulcers were demonstrated to have healed within 14 days (72%), compared with 95 of 160 (59%) on ranitidine. The difference is statistically significant (P = 0.0121). After 14 days smaller ulcers healed more quickly than large ones, regardless of the drug used: 80 of 110 with diameter 3-5 mm (73%); 48 of 90 with diameter more than 8 mm (53%). Smoking delayed healing [healing rate among non-smokers, 87 of 117 (74%); among smokers, 113 of 189 (60%)]. Healing rates among smokers receiving omeprazole and non-smokers receiving ranitidine were nearly identical. After 4 weeks, at 96 and 92% respectively, there was no difference in regard to healing rate. Both drugs had a similar influence on the symptoms. Thus, for the first time it has been demonstrated that omeprazole is superior to ranitidine after 14-day treatment of duodenal ulcer.

[Therapy of duodenal ulcer with H2-blockers. 2 x 150 mg ranitidine versus 2 x 400 mg cimetidine]. / Therapie des Ulcus duodeni mit H2-Blockern. 2 x 150 mg Ranitidin versus 2 x 400 mg Cimetidin.

60 out-patients with acute duodenal ulcers were treated in an open randomized trial with 2 x 150 mg ranitidine or 2 x 400 mg cimetidine, respectively. At endoscopy after 12 and 24 days there was evidence of complete healing in 63% and 93% in the ranitidine- and 57% and 83% in the cimetidine-treated group. Although the symptoms in both groups improved during treatment with H2-blockers, there was a more rapid relief in pain in the ranitidine-group (p less than 0.01). The more favorable results with ranitidine, 150 mg twice daily, warrant further clinical evaluation.