Current issues of ACP Journal Club are published in Annals of Internal Medicine


Therapeutics

Omeprazole for prevention of duodenal ulcer relapse

ACP J Club. 1991 Nov-Dec;115:71. doi:10.7326/ACPJC-1991-115-3-071


Source Citation

Lauritsen K, Andersen BN, Laursen LS, et al. Omeprazole mg three days a week and 10 mg daily in prevention of duodenal ulcer relapse. Double-blind comparative trial. Gastroenterology. 1991 Mar;100:663-9.


Abstract

Objective

To determine the long-term effectiveness of omeprazole in preventing relapse of duodenal ulcer disease.

Design

Randomized, double-blind, placebo-controlled trial.

Setting

Outpatient clinics in 2 tertiary care centers, Denmark.

Patients

Patients from a duodenal ulcer healing trial were eligible to participate in this trial if they had obtained pain relief and healing of ≥ 1 endoscopically documented duodenal ulcer > 5 mm in diameter, were within 3 days of finishing their healing course, and were between 18 and 80 years of age. Exclusion criteria included treatment with H2-receptor antagonists or nonsteroidal anti-inflammatory drugs, ulcer bleeding or pyloric stenosis requiring surgery, previous gastric surgery, concomitant gastric or prepyloric ulcer or other disease, pregnancy or lactation, or abnormal laboratory results in predrug screening.

Intervention

Patients were randomly allocated to receive treatment for 6 months, or until time of relapse, with omeprazole, either 20 mg 3 times/wk (Friday, Saturday, and Sunday mornings) or 10 mg every morning, or placebo. Levels of pain were self-reported using diary cards. Patients were allowed antacids for pain relief. Clinical assessments, including endoscopy and biopsy, were done at 3 and 6 months.

Main outcome measure

Relapse, defined as recurrence of ulcerlike pain for ≥ 3 days or recurrence of ulcer verified by endoscopy.

Main results

180 (92%) compliant patients completed the study. Fewer patients on placebo were in remission after 3 and 6 months than in either of the omeprazole groups (P< 0.001). At 3 months there were 11 ulcer relapses (17%) in the 20-mg omeprazole group, 15 (23%) in the 10-mg omeprazole group, and 40 (61%) in the placebo group. {95% CIs for the difference between 20-mg omeprazole and placebo were 29% to 59%, and between 10-mg omeprazole and placebo, 22% to 53%.} Between 3 and 6 months the number of relapses occurring with omeprazole, 20 mg, 10 mg, and placebo were 5 (8%),4 (6%) and 12 (18%), respectively. (Cls for the difference between 20-mg omeprazole and placebo were 1 % to 22%; and 1 % to 23% for 10-mg omeprazole and placebo.) The rates of relapse in the 2 omeprazole groups did not differ. Side effects were few and minor.

Conclusion

Treatment with omeprazole, 20 mg 3 days/ wk or 10 mg daily, appears to be safe and effective in preventing relapse of duodenal ulcer.

Source of funding: In part, A.B. Hässle.

Address for article reprint: Dr. K. Lauritsen, Department of Medical Gastroenterology, Odense University Hospital, DK-5000 Odense C, Denmark.


Commentary

Omeprazole may emerge as the drug of choice for the management of peptic ulcer disease, but its rank among currently available therapies has not yet been established. This is a thorough study addressing drug safety and efficacy in the prophylaxis of duodenal ulcers. The authors also introduce the concept of pulse (3 consecutive days/ wk) therapy for ulcer prophylaxis.

Because omeprazole, a parietal-cell proton-pump inhibitor, is such an effective acid inhibitor, concerns about systemic and gastric side effects remain. These authors closely monitored the morphologic changes in the gastric mucosa of all patients as well as serum gastrin levels and did not detect any statistically significant changes over the 6-month study period. Such findings are reassuring.

The study population was unique in certain characteristics. The mean duration of ulcer history ranged from 7 to 10 years in the 3 study groups; 79% of patients smoked at entry; and all patients favorably responded to higher-dose omeprazole for their active ulcer disease. As a result, the success reported may apply only to patients with chronic, recurrent documented duodenal ulcers.

Dyspeptic complaints are common among the patients of all clinicians. The role of omeprazole in the treatment of symptomatic patients without demonstrated pathologic changes remains to be established. This treatment is expensive (average wholesale price = $3.32 /20-mg tablet). Lower dosage requirements, pulse therapy, or higher response rates may make omeprazole the right choice for various acid-related upper gastrointestinal complaints. Currently, however, this drug's role is limited to a few clinical situations in which other agents, such as H2-antagonists, have proved ineffective.

John D. Goodson, MD
Massachusetts General Hospital Boston, Massachusetts