The aim of this study is to compare the efficacy of a proton pump inhibitor (lansoprazole) and a histamine-2 receptor antagonist (famotidine) in preventing recurrent ulcer bleeding in patients with a history of H. pylori-negative idiopathic peptic ulcers.

Peptic ulcer disease used to be caused by a bacterial infection (Helicobacter pylori) in the stomach or the use of certain painkillers (nonsteroidal anti-inflammatory drugs or NSAIDs). However, there has been an increasing trend of peptic ulcer disease with unknown cause (idiopathic ulcer) worldwide since the last decade. Studies in North America found that idiopathic ulcers accounted for 11% and 44% of all peptic ulcers. A meta-analysis of 7 US trials found that 20% of patients with H. pylori-associated ulcers had recurrent ulcers within 6 months, despite successful cure of H. pylori infection and no reported use of NSAIDs. In a pooled analysis of 6 clinical trials with a total of 2900 patients, 27% of duodenal ulcers were not associated with NSAID use or H. pylori infection. The emerging problem of H. pylori-negative idiopathic peptic ulcers is not only limited to western countries. Previously, H. pylori-negative idiopathic peptic ulcers accounted for less than 5% of peptic ulcers in Asia. A recent Korean study reported that the proportion of peptic ulcers not associated with H. pylori infection or NSAID use was over 20%.

Inclusion Criteria:

1. A history of H. pylori-negative idiopathic peptic ulcers, defined as

   1. No exposure to aspirin, NSAIDs or drugs of unknown nature including traditional Chinese medicine within the 4 weeks before hospitalization;
   2. Biopsies taken during endoscopy must be negative for both the urease test and histology for H. pylori in the absence of acid suppressive therapy; and
   3. No other causes of ulceration identified.

2. Endoscopically confirmed ulcer healing

3. Age >18 years old

4. Informed consent

Exclusion Criteria:

1. Concomitant steroid or anticoagulant
2. Concomitant use of NSAIDs, aspirin or COX2 inhibitors
3. Previous gastric surgery
4. Requirement of maintenance PPI (e.g. reflux oesophagitis)
5. Advanced comorbidity (defined as ASA 4 or above) or active malignancy
6. Subjects who are pregnant or lactating, or is intending to become pregnant before, during, or within 1 month after participating in this study
7. Subjects who have known hypersensitivity or allergies to any component of lansoprazole or famotidine.
8. Subject who has current or historical evidence of Zollinger-Ellison syndrome or other hypersecretory condition