PPI vs H2RA in Patients With Helicobacter Pylori-Negative Idiopathic Bleeding Ulcers

Sponsor

Chinese University of Hong Kong (Other)

Overall Status

Completed

CT.gov ID

NCT01180179

Collaborator

(none)

228

Enrollment

Location

Arms

107

Actual Duration (Months)

2.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Peptic Ulcer	Drug: Lansoprazole Drug: Famotidine	Phase 4

Detailed Description

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%.

Study Design

Study Type:

Interventional

Actual Enrollment :

228 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Prevention

Official Title:

Prevention of Recurrent Idiopathic Gastroduodenal Ulcer Bleeding: a Double-blind Randomized Trial

Actual Study Start Date :

Jun 1, 2010

Actual Primary Completion Date :

May 1, 2019

Actual Study Completion Date :

May 1, 2019

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Lansoprazole 30mg once daily Lansoprazole 30mg once daily	Drug: Lansoprazole 30mg once daily
Active Comparator: Famotidine 40mg once daily Famotidine 40mg once daily	Drug: Famotidine 40mg once daily

Arm

Intervention/Treatment

Active Comparator: Lansoprazole 30mg once daily

Lansoprazole 30mg once daily

Drug: Lansoprazole

30mg once daily

Active Comparator: Famotidine 40mg once daily

Famotidine 40mg once daily

Drug: Famotidine

40mg once daily

Outcome Measures

Primary Outcome Measures

Recurrent ulcer bleeding [24 months]
According to prespecified criteria - hematemesis or melena documented by the admitting physician, or a decrease in the hemoglobin level of at least 2 g/dL, with ulcers or bleeding erosions confirmed on endoscopy. A prespecified interim-analysis is performed on the primary endpoint when all patients have been randomised and have completed the 12 months follow-up. The interim-analysis is performed by an independent statistician, blinded for the treatment allocation. The statistician will report to the independent data and safety monitoring committee (DSMC). The DSMC will have unblinded access to all data and will discuss the results of the interim-analysis with the steering committee in a joint meeting. The steering committee decides on the continuation of the trial and will report to the central ethics committee. The Peto approach is used: the trial will be ended using symmetric stopping boundaries at P < 0.001.

Secondary Outcome Measures

Recurrent ulcer detected by endoscopy at 24-month [at the 24th month of follow-up]
Recurrent ulcer detected by endoscopy at 24-month, with or without clinical symptoms.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

A history of H. pylori-negative idiopathic peptic ulcers, defined as
No exposure to aspirin, NSAIDs or drugs of unknown nature including traditional Chinese medicine within the 4 weeks before hospitalization;
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
No other causes of ulceration identified.
Endoscopically confirmed ulcer healing
Age >18 years old
Informed consent

Exclusion Criteria:

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