Primary gastroduodenal prophylaxis with omeprazole for non-steroidal anti-inflammatory drug users.

AIM: To investigate the efficacy of omeprazole 20 mg o.m. as primary prophylaxis against non-steroidal anti-inflammatory drug (NSAID)-associated ulcer disease or dyspeptic symptoms. METHODS: A parallel group study compared patients randomized to receive omeprazole 20 mg o.m. or placebo as co-therapy with on-going NSAID treatment, over 6 months, in 19 specialist centres in Ireland, Hungary, France, the UK and the USA. One hundred and sixty-nine patients taking NSAIDs regularly, chronically and above defined minimum doses entered the trial. The main outcome measure was the development of gastric or duodenal ulcers detected endoscopically, the development of multiple erosions in the stomach or duodenum, or the onset of moderate or severe dyspeptic symptoms. RESULTS: The estimated probability of remaining free of these end-points for 6 months for patients taking omeprazole was 0.78 compared to 0.53 for placebo (P = 0.004). Fourteen patients receiving placebo (16.5%) developed 15 ulcers, comprising nine gastric and six duodenal ulcers, compared to three patients (3.6%) receiving omeprazole (all gastric ulcers). Logistic regression analysis showed that older patients were less likely, whilst those with rheumatoid arthritis were more likely, to remain free of NSAID-associated problems. CONCLUSIONS: Omeprazole is an effective agent for gastroduodenal prophylaxis in patients taking NSAIDs. Its main effect is to reduce the rate of development of gastric and duodenal ulcers.

Lansoprazole heals erosive reflux esophagitis resistant to histamine H2-receptor antagonist therapy.

PURPOSE: We conducted a randomized, double-blind, multicenter clinical trial to determine whether lansoprazole was superior to continued therapy with histamine H2-receptor antagonist therapy in healing erosive reflux esophagitis. METHODS: Investigators from nine medical centers enrolled 159 patients with endoscopically documented esophageal erosions and/or ulcers that had failed to heal with 12 or more wk of at least standard dosages of histamine H2-receptor antagonist therapy. Patients received ranitidine 150 mg b.i.d. for 8 wk or lansoprazole 30 mg for 4 wk followed by either lansoprazole 30 mg or lansoprazole 60 mg for another 4 wk of treatment. Patients underwent endoscopy at screening and at weeks 2, 4, and 8. RESULTS: At 2, 4, and 8 wk of therapy, healing rates were significantly higher in the lansoprazole group compared with the ranitidine group (p < 0.001). By 8 wk, 84% of the lansoprazole group were healed as opposed to only 32% of the ranitidine group. Lansoprazole was superior to ranitidine in providing relief of upper abdominal burning and daytime heartburn (p < 0.001) and reducing the need for antacids (p < 0.001). Lansoprazole patients had less interference with sleep and less day time drowsiness than ranitidine patients (p = 0.05). The percentages of patients with adverse events were similar in both groups. Fasting serum gastrin levels at weeks 4 and 8 were significantly higher in the lansoprazole group compared with the ranitidine group. CONCLUSION: Eight weeks of lansoprazole therapy is safe, superior to continued ranitidine therapy, and effective in healing more than 80% of patients with erosive reflux esophagitis previously resistant to histamine H2-receptor antagonist therapy.

Comparison of once-daily doses of omeprazole (40 and 20 mg) and placebo in the treatment of benign gastric ulcer: a multicenter, randomized, double-blind study.

OBJECTIVE: The purpose of this multicenter, randomized, double-blind study, conducted in 520 patients, was to compare the efficacy and safety of omeprazole (40 and 20 mg once daily) with placebo in the treatment of benign gastric ulcer. METHODS: Treatment with omeprazole or placebo lasted 4 wk; those whose ulcers remained unhealed continued the same treatment regimen for an additional 4 wk. The effects of therapy were determined by endoscopy and assessment of GI symptoms. Safety and tolerability were evaluated through reported adverse events, physical examinations, and laboratory tests. RESULTS: At weeks 4 and 8, the proportion of patients with healed ulcers was significantly greater in the omeprazole 40- and 20-mg groups than in the placebo group (p < 0.01). At week 8, the healing rate was significantly greater in the 40-mg group than in the 20-mg group (82.7 vs 74.8%, p < 0.05). In patients with large ulcers (>1 cm), the 40-mg regimen was associated with a significantly higher healing rate (78.9%) than both the 20-mg regimen (61.4%) and placebo (34.6%) at week 8 (p < 0.05 vs omeprazole 20 mg; p < 0.01 vs placebo). Healing rates in patients with small ulcers were similar for the 40- and 20-mg groups. Omeprazole was well tolerated, with no significant differences versus placebo in the overall incidence of clinical or laboratory adverse events. CONCLUSIONS: Omeprazole 40 and 20 mg, administered once daily, healed a significantly greater proportion of patients than did placebo. The 40-mg regimen offered significant advantages over the 20-mg regimen in patients with large ulcers.

Omeprazole versus ranitidine or ranitidine/metoclopramide in poorly responsive symptomatic gastroesophageal reflux disease.

OBJECTIVES: To evaluate complete symptom resolution, mucosal healing, and tolerability of omeprazole, ranitidine, or ranitidine/metoclopramide in patients with poorly responsive, symptomatic gastroesophageal reflux disease (GERD). METHODS: Adults with persistent symptomatic GERD after ranitidine treatment were stratified by esophagitis grade and randomized to omeprazole 20 mg once daily, ranitidine HCI 150 mg twice daily, or ranitidine HCI 150 mg twice daily plus metoclopramide HCI 10 mg four times daily. Endoscopies were conducted at baseline and at wk 4 and 8. Patients assessed overall symptom improvement at wk 4 and 8 and evaluated daytime and nighttime heartburn, dysphagia, and acid regurgitation daily. RESULTS: After 1 wk, 13% of patients receiving omeprazole (N = 100) had complete resolution of all GERD symptoms versus 1% and 3% of patients receiving ranitidine (N = 97) or ranitidine/metoclopramide (N = 93), respectively (p < 0.001). More patients receiving omeprazole had complete symptom resolution at wk 4 (33%) and at the end of the study (64%; both p < 0.001) than patients receiving ranitidine (8% and 28%, respectively) or ranitidine/metoclopramide (7% and 29%, respectively). Regardless of baseline esophagitis grade, more patients receiving omeprazole had complete symptom resolution. At wk 8, more than 91% of patients with grade 0 or 1 esophagitis at baseline were still healed irrespective of treatment. At wk 8, 80% of patients with esophagitis grade 2 or higher at entry were healed with omeprazole (p < 0.001 vs ranitidine [40%] and ranitidine/metoclopramide [46%]). Thirty-four percent of patients reported an adverse event. Significantly more patients receiving combination treatment reported an adverse event than patients treated with single agents. CONCLUSIONS: In patients with persistent GERD symptoms after ranitidine, omeprazole (20 mg daily for up to 8 wk) provides faster and more complete resolution of common GERD symptoms than continued ranitidine (300 mg daily) alone or in combination with metoclopramide (40 mg daily). Omeprazole provides significantly higher rates of endoscopic healing than ranitidine alone or with metoclopramide. Omeprazole and ranitidine are generally well tolerated. The addition of metoclopramide to ranitidine significantly increases adverse events.

Lansoprazole prevents recurrence of erosive reflux esophagitis previously resistant to H2-RA therapy. The Lansoprazole Maintenance Study Group.

OBJECTIVE: This randomized, double-blind study was designed to determine whether the proton pump inhibitor lansoprazole could prevent relapse among patients with healed erosive reflux esophagitis that had been resistant to healing with at least 3 months of H2-receptor antagonist therapy. RESULTS: By the end of the year, 13% of placebo patients remained healed compared with 67% of lansoprazole 15 mg and 55% of lansoprazole 30 mg patients (p < 0.001 for time to first relapse). All placebo patients were symptomatic by the end of the study whereas only one-third of the lansoprazole patients was symptomatic at the end of the 12-month study period. The two lansoprazole doses were comparably effective in maintaining healing and in symptom control and were well tolerated. Fasting serum gastrin values increased significantly to about 1.5-2 times the baseline values over the first 2 months of lansoprazole treatment; no further increase was noted. CONCLUSION: Erosive relapse can be prevented in most patients for up to 1 yr with lansoprazole 15 mg or 30 mg once daily.

Efficacy of once-daily cimetidine in preventing recurrence of duodenal ulcer.

In a prospective multicenter trial, 88 patients with acute duodenal ulcers that were healed with ranitidine were randomly assigned to receive maintenance treatment with either cimetidine 400 mg (n = 45) or placebo (n = 43) at bedtime for six months. Ten percent of the patients experienced moderate or severe pain both during the day and at night while on placebo during the maintenance phase. The average proportion of cimetidine patients experiencing moderate or severe pain during the day or night was 50% and 80% lower than placebo, respectively. Ulcer-like symptoms prompted endoscopy in 44% (19 of 43) of the placebo patients compared with 18% (eight of 45) of patients receiving cimetidine (P = 0.009). At the completion of the maintenance study, cumulative symptomatic ulcer recurrence rates were 28% (12 of 43) for those on placebo compared with 13% (six of 45) for cimetidine patients. The adverse drug effects noted were similar between treatment groups, with no unexpected reactions reported. A low dose of cimetidine (400 mg) at bedtime effectively reduced the incidence of gastrointestinal symptoms that were severe enough to prompt endoscopy as well as the actual recurrence of ulcers in those patients who had responded to initial therapy with ranitidine, but who continued to be at increased risk of reulceration.

The efficacy of cimetidine in the treatment of "resistant" duodenal ulcers.

In a prospective multicenter trial, 43 patients with acute duodenal ulcers unhealed after four weeks of treatment with an H2-receptor antagonist, ranitidine, were switched to treatment with another H2-receptor antagonist, cimetidine. Sixty-eight percent of the unhealed patients were successfully healed; of these patients, 81% were free of daytime pain and 89% were free of nighttime pain. Of those with residual pain, 71% and 50% showed improvement in daytime and nighttime pain severity, respectively. There were no unexpected adverse reactions reported or clinically significant changes in laboratory values measured during the study. It is concluded that cimetidine is highly effective both in healing duodenal ulcers unresponsive to ranitidine therapy and in providing continued relief of daytime and nighttime pain.

Effect of ranitidine on gastroduodenal mucosal damage induced by nonsteroidal antiinflammatory drugs.

The effect of ranitidine in preventing mucosal damage caused by nonsteroidal antiinflammatory drugs (NSAIDs) was evaluated for eight weeks in a prospective study of 144 patients requiring NSAIDs. Patients with normal endoscopic findings were randomly assigned to receive either ranitidine 150 mg twice daily or placebo for eight weeks, along with either ibuprofen, indomethacin, naproxen, sulindac, or piroxicam. Duodenal damage was significantly less in the ranitidine group compared with the placebo group by weeks 4 and 8 (P less than or equal to 0.01). Duodenal ulcers did not develop in any patients on ranitidine (0/57) compared with 4/49 patients (8%) on placebo (P = 0.02). No significant difference was found between treatment groups with respect to gastric damage; 6/60 (10%) in the ranitidine group compared with 6/50 (12%) in the placebo group developed gastric ulcers. These findings suggest that acid suppression is of greater importance for mucosal protection in the duodenum than in the stomach, where other defense mechanisms may be operative. While ranitidine is an effective prophylaxis for NSAID-induced damage in the duodenum, further studies are needed to define specific risk groups and to assess the potential usefulness of more complete acid suppression in preventing gastric mucosal damage.