Daily omeprazole surpasses intermittent dosing in preventing relapse of oesophagitis: a US multi-centre double-blind study.

INTRODUCTION: Relapse of erosive oesophagitis occurs in almost all patients if treatment is stopped after initial healing. AIM: To assess the potential of different therapeutic regimens of omeprazole to prevent relapse of erosive reflux oesophagitis after initial healing with omeprazole. PATIENTS AND METHODS: Patients whose active erosive reflux oesophagitis (grade > or = 2) had healed (grade 0 or 1) after 4-8 weeks of open-label omeprazole 40 mg daily (phase I) were eligible to join a multi-centre, 6-month double-blind, placebo-controlled maintenance study (phase II), which included endoscopy, symptom assessments, serum gastrin measurements, and gastric fundic biopsies. During phase I, endoscopy was performed at weeks 0, 4, and 8. At the end of phase I, 429 of 472 patients (91%) were healed, and there were significant reductions in heartburn, dysphagia and acid regurgitation. Of the 429 patients who healed, 406 joined phase II and were randomized to one of three groups: 20 mg omeprazole daily (n = 138), 20 mg omeprazole for 3 consecutive days each week (n = 137), or placebo (n = 131). During phase II, endoscopy was performed at months 1, 3, and 6 or at symptomatic relapse. RESULTS: The percentages of patients still in endoscopic remission at 6 months were 11% for placebo, 34% for omeprazole 3-days-a-week, and 70% for omeprazole daily. Both omeprazole regimens were superior to placebo in preventing recurrence of symptoms (P < 0.001); however, omeprazole 20 mg daily was superior to omeprazole 20 mg 3-days-a-week (P < 0.001). Compared to baseline, omeprazole therapy resulted in no significant differences among treatment groups in the distribution of gastric endocrine cells. CONCLUSIONS: These results show that after healing of erosive oesophagitis with 4-8 weeks of omeprazole, relapse of oesophagitis and recurrence of reflux symptoms can be prevented in 70% of patients with a maintenance regimen of 20 mg daily, but that intermittent dosing comprising 3 consecutive days each week significantly compromises efficacy.

Mesalamine capsules for treatment of active ulcerative colitis: results of a controlled trial. Pentasa Study Group.

The efficacy of a capsule formulation of mesalamine was assessed in 374 patients with mild to moderately active ulcerative colitis. Patients, stratified to pancolitis or left-sided disease, received either placebo or mesalamine at 1, 2, or 4 g daily for 8 wk. Efficacy was assessed using clinical improvement--physician global assessment, sigmoidoscopic index, biopsy score, trips to the toilet, and clinical symptoms (abdominal pain, urgency, stool consistency, and rectal bleeding)--and induction of remission (more stringent criteria for physician global assessment, sigmoidoscopic index, and biopsy score). For physician global assessment of treatment benefit, 79% and 84% of patients on the 2-g and 4-g doses of mesalamine, respectively, received treatment benefit, compared with 54% on placebo (p < or = 0.0002). For the physician global assessment of treatment success, both the 2-g and 4-g doses of mesalamine were superior to placebo (57% and 59% of patients, p = 0.0021 and 0.0012, respectively), compared with 36% on placebo. Both the 2-g and 4-g doses produced statistically significant macroscopic (endoscopic) improvement compared with placebo (p < 0.004). The 4-g dose also produced a statistically significant microscopic (histologic) improvement compared to placebo (p < 0.002). Significant improvement compared to placebo was also observed at 2 g and 4 g for the four clinical symptoms and trips to the toilet (p < or = 0.003). Oral mesalamine capsules were significantly superior to placebo for inducing remission, with 29% of patients at 2 g and 29% at 4 g achieving remission by physician global assessment, compared with 12% on placebo. Forty-four percent and 48% of patients receiving 2 g and 4 g of mesalamine, respectively, achieved remission by sigmoidoscopic index (p < 0.05), compared with 31% on placebo. Thirty-nine percent of patients at 4 g daily achieved microscopic remission, compared with 23% on placebo (p < 0.03). Treatment response was not affected by extent of disease or prior steroid or sulfasalazine therapy. These data suggest that controlled-release mesalamine capsules are a safe and effective monotherapy in doses of 2-4 g daily for treating mild to moderately active ulcerative colitis, as well as for inducing remission, regardless of prior oral steroid or sulfasalazine therapy or extent of disease.

Omeprazole is superior to ranitidine plus metoclopramide in the short-term treatment of erosive oesophagitis.

Histamine H2-receptor antagonists are moderately effective in symptomatic treatment and healing of erosive oesophagitis, but they are not as effective as the proton pump inhibitor omeprazole. In some studies prokinetic agents seem to increase the effectiveness of H2-antagonists, but no study comparing the efficacy of omeprazole to H2-antagonists plus prokinetic agents has been performed. The purpose of this study was to compare the efficacy and tolerability of 20 mg omeprazole daily with 150 mg ranitidine b.d.s. plus the prokinetic agent 10 mg metoclopramide q.d.s. in patients with erosive oesophagitis. After both 4 and 8 weeks of treatment, omeprazole healed the mucosa in significantly more patients than did ranitidine plus metoclopramide. Omeprazole also provided significantly greater relief from daytime heartburn, nighttime heartburn, and acid regurgitation, and was associated with decreased concomitant antacid use. Although the overall incidence of adverse events was similar in the two treatment groups, a significantly higher number of treatment-related adverse events and more treatment-related withdrawals from the study occurred in the ranitidine plus metoclopramide treatment group. Omeprazole is more effective and better tolerated than the combination of standard dose ranitidine plus metoclopramide for patients with erosive oesophagitis.

Ranitidine for erosive oesophagitis: a double-blind, placebo-controlled study. Glaxo Erosive Esophagitis Study Group.

A multicentre, randomized, double-blind, placebo-controlled study was conducted to evaluate the efficacy and safety of ranitidine 150 mg and 300 mg in 342 patients with erosive oesophagitis. Treatment was given four times daily, and continued for 12 weeks or until healing (that is, normal or only erythematous mucosa). Erosive oesophagitis healing rates, as determined by endoscopy, were significantly greater in ranitidine-treated patients by 4 weeks compared with those of placebo-treated patients. By 12 weeks, erosive oesophagitis healing rates were 83 and 81% for ranitidine-treated patients (150 and 300 mg, respectively) and 58% for placebo-treated patients (P less than or equal to 0.001, ranitidine vs. placebo). Symptomatic relief was achieved within 24 hours after starting either dosage of ranitidine. Heartburn frequency (P less than 0.001) and severity (P less than 0.001), as well as antacid consumed per week (P less than 0.001), were reduced in both ranitidine groups in comparison with placebo. Healing rates and symptom relief were similar in the two ranitidine groups. Both dosages of ranitidine were well tolerated. Ranitidine (150 mg) given four times daily appears to be as effective as 300 mg ranitidine given four times daily in patients with moderate to severe oesophageal erosions.

Omeprazole versus placebo in duodenal ulcer healing. The United States experience.

The study objective was to study the ulcer healing effects and safety of the proton pump inhibitor, omeprazole, given in a dose of 20 mg once daily before breakfast. The study design was a randomized, double-blind, multicenter comparison of omeprazole and placebo using endoscopy to assess ulcer healing after two or four weeks of therapy. One hundred fifty-three patients with endoscopically documented active duodenal ulcer were studied. One hundred two patients received omeprazole and 51 received placebo. Patients in both groups were similar with regard to age, sex, duration of disease, initial ulcer size, smoking history, and alcohol use. A "per protocol" analysis of healing rates showed a significant advantage for omeprazole (P less than 0.01) at both week 2 (41% vs 13%) and week 4 (75% vs 27%). Concomitant factors (including smoking and ulcer size) did not alter the significance of the differences in healing rates between omeprazole and placebo. Complete relief of day and night pain was more often achieved (P less than 0.01) in the omeprazole group. "All-patients treated" analyses for healing and pain relief gave results similar to the respective "per protocol" analyses. Omeprazole was well tolerated; fewer patients had clinical and laboratory adverse experiences in the omeprazole group than in the placebo group. Fasting serum gastrin levels increased with omeprazole therapy (mean 34.9 to 73.5 pg/ml) but exceeded the normal range (greater than 150 pg/ml) in only 12.3% of patients. Two weeks after therapy was stopped, serum gastrin levels showed a decrease toward baseline but had not yet completely returned to pretreatment levels (mean 49.7 pg/ml).(ABSTRACT TRUNCATED AT 250 WORDS)

Suppression of nocturnal acid secretion with famotidine accelerates gastric ulcer healing.

Although nocturnal acid secretion has been emphasized in the pathophysiology and treatment of duodenal ulcer, its importance in gastric ulcer disease has been questioned. To explore this area, this multicenter U.S. trial compared the effect of a once-daily nighttime dose of H2-receptor antagonist with placebo on the healing of gastric ulcer and relief of associated symptoms. One hundred fifty-seven patients with endoscopically verified benign gastric ulcers were randomized in a double-blind fashion to either famotidine (40 mg at bedtime) or placebo. Antacid tablets were allowed as needed. The healing rates for famotidine were 45%, 66%, and 78% at weeks 4, 6, and 8, respectively. In comparison, placebo healing rates were 39%, 44%, and 64%. These differences were statistically significant in favor of famotidine at weeks 6 (p less than or equal to 0.01) and 8 (p less than or equal to 0.05), as well as in a life-table analysis (p less than or equal to 0.05). Nocturnal famotidine was also significantly better than placebo with respect to time to complete relief of pain and to the percentage of patients with complete relief of pain. No concomitant factor (including ulcer size, ulcer location, smoking history, or regular alcohol use) affected healing rates in this study. Famotidine was well-tolerated and no serious clinical or laboratory adverse effects were judged to be related to this dosing regimen of famotidine. In conclusion, suppression of nocturnal acid secretion with famotidine (40 mg at bedtime) was more effective than placebo in promoting the healing of acute benign gastric ulcer and its associated symptoms. The results of this study suggest that suppression of nocturnal acid secretion alone is as effective as "around the clock" acid suppression in the healing of benign gastric ulcer.

Multicenter trial of sucralfate suspension for the treatment of reflux esophagitis.

The efficacy of sucralfate suspension in the treatment of reflux esophagitis was assessed in a multicenter, randomized, double-blind, placebo-controlled trial. Sixty-eight patients with symptomatic and endoscopic esophagitis received either sucralfate suspension (n = 31) or liquid placebo (n = 37) for eight weeks. The two groups were comparable at entry with the exception that despite randomization, a disproportionately high number of patients with esophageal ulcers were assigned to receive sucralfate. After four and eight weeks of treatment, both groups had reduced heartburn frequency and severity, but there was no difference in improvement between sucralfate and placebo (p greater than 0.05). Endoscopic results after eight weeks of sucralfate treatment revealed complete healing in 36 percent (placebo, 35 percent) and improvement in an additional 45 percent (placebo, 24 percent). Although neither of these differences was significant, the percent of patients in whom healing or improvement occurred with sucralfate (81 percent) was greater than with placebo (59 percent) (p = 0.07). These data fail to establish that eight weeks of treatment with sucralfate suspension improves symptoms or heals lesions in reflux esophagitis at a rate significantly greater than placebo. However, the unequal distribution of patients with ulcers and the trend toward endoscopic improvement indicate that a potential beneficial effect of sucralfate suspension for the treatment of reflux esophagitis cannot be excluded.

Efficacy of sucralfate in the prevention of recurrence of duodenal ulcers.

Eighty-four patients who were endoscopically confirmed to have healed duodenal ulcers were entered into this 1-year, double-blind, placebo-controlled trial of sucralfate, 1g twice daily, in the prevention of duodenal ulcer recurrence. Patients remained in the study until recurrence of ulceration was endoscopically confirmed. Sixty-one patients could be evaluated for efficacy of treatment. Within 6 months, 23 of 31 placebo patients (74%) and 6 of 30 sucralfate patients (20%) had ulcer recurrence. At 12 months, 25 of 31 placebo patients (80%) and 8 of 30 receiving sucralfate (27%) had ulcer recurrence. The lower rate of ulcer recurrence in patients receiving sucralfate was significant (p = 0.0001). Survival curves also showed that sucralfate was significantly more effective in preventing relapse (p = 0.0001). Three patients were judged as experiencing drug-related side effects, two of which were in the placebo group. The results indicate that sucralfate is significantly more effective than placebo in the prevention of recurrence of duodenal ulcer disease.

Efficacy of misoprostol (twice daily dosage) in acute healing of duodenal ulcer. A multicenter double-blind controlled trial.

This study was undertaken to evaluate the efficacy of misoprostol taken twice daily for the healing of duodenal ulcer. Three hundred thirty patients with endoscopically proven duodenal ulcer participated in a multicenter, double-blind, controlled trial comparing placebo with misoprostol 200 micrograms and 400 micrograms twice daily for up to four weeks. Patient characteristics were similar in all three treatment groups. Ulcers were between 0.3 cm and 2.0 cm in length. Healing was determined by endoscopy at two weeks; if ulcers were not healed, endoscopy was repeated at four weeks. All patients were given Al(OH)3 antacid (up to 54 meq a day) to be used as needed for pain. Healing rates at four weeks for a total of 280 evaluable patients in the three treatment groups were as follows: misoprostol 400 micrograms bid, 65.4%; misoprostol 200 micrograms bid, 52.9%; and placebo, 42.2%. Misoprostol 400 micrograms bid was superior to placebo (P = 0.002) in healing ulcers. However, the healing rate for misoprostol 200 micrograms bid did not differ significantly from placebo. The percentage of nonsmokers who healed at four weeks was higher than that of smokers in both misoprostol-treatment groups, although the difference was not analyzed for statistical significance. There were no differences in antacid consumption or pain relief among the three experimental groups during the study. Diarrhea was the most common side effect but was mild and self-limiting, occurring in 8.9%, 5.9%, and 1.8% of the misoprostol 400 micrograms, 200 micrograms, and placebo groups, respectively. These results indicate that misoprostol 400 micrograms taken twice daily for four weeks is effective and safe for the treatment of duodenal ulcers.

Misoprostol, a synthetic PGE1 analog, in the treatment of duodenal ulcers. A multicenter double-blind study.

Misoprostol, a synthetic analog of prostaglandin E1, inhibits gastric acid production and is cytoprotective at doses well tolerated by patients in preliminary trials. This multicenter double-blind study was performed in out-patients with endoscopically demonstrated duodenal ulcers, to compare the efficacy in ulcer healing and the safety of two dosages of misoprostol and placebo. Up to six antacid tablets daily were permitted for pain. 308 patients enrolled and were randomized to three treatment groups: placebo, misoprostol 50 micrograms and misoprostol 200 micrograms. After two weeks of treatment, the three groups had similar percentages of patients with complete ulcer healing. However, after four weeks, 76.6% of patients taking misoprostol 200 micrograms q.i.d. had complete healing, compared with 42.6% on misoprostol 50 micrograms q.i.d. and 51% on placebo (P less than 0.001, 200 micrograms versus placebo). Patients taking misoprostol 200 micrograms used less antacid than the others. Diarrhea, mild and self-limiting, was present in 13% of the 200 micrograms group versus 5% on placebo. We conclude that misoprostol 200 micrograms q.i.d. is effective, safe and well tolerated in the treatment of duodenal ulcers.

Medical management of patients with reflux esophagitis.

Medical management of reflux esophagitis includes physical manipulations, antacids, and antireflux medications (bethanechol and alginic acid). Their combined usage in the continuous dyspeptic and the problem case help "break the cycle," providing relief for long periods of time. Identification of possible inciting factors in cases of recurrence should be pointed out to the patient so that he will develop an instinctive antireflux behavior. The effect of this combined therapy on the pathophysiology and natural history of the disease remains to be determined.