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

• ClinicalTrials.gov Identifier: NCT01180179
• Recruitment Status: Completed
• First Posted: August 12, 2010
• Last Update Posted: August 1, 2019
• Sponsor: Chinese University of Hong Kong
• Information provided by (Responsible Party): Francis KL Chan, Chinese University of Hong Kong

Tracking Information

• First Submitted Date: August 3, 2010
• First Posted Date: August 12, 2010
• Last Update Posted Date: August 1, 2019
• Actual Study Start Date: June 2010
• Actual Primary Completion Date: May 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 15, 2017)

Recurrent ulcer bleeding [ Time Frame: 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.

Original Primary Outcome Measures (submitted: August 11, 2010)

Recurrent ulcer bleeding [ Time Frame: 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.

Current Secondary Outcome Measures (submitted: August 24, 2012)

Recurrent ulcer detected by endoscopy at 24-month [ Time Frame: at the 24th month of follow-up ]

Recurrent ulcer detected by endoscopy at 24-month, with or without clinical symptoms.

Original Secondary Outcome Measures (submitted: August 11, 2010)

Recurrent ulcer detected by end-of-study endoscopy [ Time Frame: at the 24th month of follow-up ]

Recurrent ulcer detected by end-of-study endoscopy, with or without clinical symptoms.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: PPI vs H2RA in Patients With Helicobacter Pylori-Negative Idiopathic Bleeding Ulcers
• Official Title: Prevention of Recurrent Idiopathic Gastroduodenal Ulcer Bleeding: a Double-blind Randomized Trial
• 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.
• 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 Type: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Prevention
• Condition: Peptic Ulcer

Intervention

• Drug: Lansoprazole
  30mg once daily
• Drug: Famotidine
  40mg once daily

Study Arms

• Active Comparator: Lansoprazole 30mg once daily
  Lansoprazole 30mg once daily
  Intervention: Drug: Lansoprazole
• Active Comparator: Famotidine 40mg once daily
  Famotidine 40mg once daily
  Intervention: Drug: Famotidine

• Publications *: Wong GLH, Lau LHS, Ching JYL, Tse YK, Ling RHY, Wong VWS, Chiu PWY, Lau JYW, Chan FKL. Prevention of recurrent idiopathic gastroduodenal ulcer bleeding: a double-blind, randomised trial. Gut. 2020 Apr;69(4):652-657. doi: 10.1136/gutjnl-2019-318715. Epub 2019 Jun 22.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: February 28, 2013): 228
• Original Estimated Enrollment (submitted: August 11, 2010): 170
• Actual Study Completion Date: May 2019
• Actual Primary Completion Date: May 2019 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: China

Administrative Information

• NCT Number: NCT01180179
• Other Study ID Numbers: NNH_RCT
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: Francis KL Chan, Chinese University of Hong Kong
• Study Sponsor: Chinese University of Hong Kong
• Collaborators: Not Provided

Investigators

• Principal Investigator: Grace L Wong, MD; Chinese University of Hong Kong

• PRS Account: Chinese University of Hong Kong
• Verification Date: July 2019