## Protocol Section
### Identification Module
**NCT ID:** NCT01180179

**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

#### Organization Study ID Info
**ID:** NNH_RCT
#### Organization
**Class:** OTHER
**Full Name:** Chinese University of Hong Kong
### Status Module
#### Completion Date
**Date:** 2019-05

**Type:** ACTUAL

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2019-08-01

**Type:** ACTUAL

**Last Update Submit Date:** 2019-07-31

**Overall Status:** COMPLETED

#### Primary Completion Date
**Date:** 2019-05

**Type:** ACTUAL

#### Start Date
**Date:** 2010-06

**Type:** ACTUAL

**Status Verified Date:** 2019-07

#### Study First Post Date
**Date:** 2010-08-12
**Type:** ESTIMATED
**Study First Submit Date:** 2010-08-03
**Study First Submit QC Date:** 2010-08-11
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** Chinese University of Hong Kong

#### Responsible Party

**Investigator Affiliation:** Chinese University of Hong Kong

**Investigator Full Name:** Francis KL Chan

**Investigator Title:** Professor

**Type:** PRINCIPAL_INVESTIGATOR

### Oversight Module

**Oversight Has DMC:** True

### Description Module

**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%.

### Conditions Module

**Conditions:**

- Peptic Ulcer

**Keywords:**

- H. pylori-negative idiopathic peptic ulcers

- Recurrent ulcer bleeding

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** PARALLEL

##### Masking Info

**Masking:** QUADRUPLE

**Who Masked:**

- PARTICIPANT

- CARE_PROVIDER

- INVESTIGATOR

- OUTCOMES_ASSESSOR

**Primary Purpose:** PREVENTION

#### Enrollment Info

**Count:** 228

**Type:** ACTUAL

**Phases:**

- PHASE4

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Lansoprazole 30mg once daily

**Intervention Names:**

- Drug: Lansoprazole

**Label:** Lansoprazole 30mg once daily

**Type:** ACTIVE_COMPARATOR

#### Arm Group 2

**Description:** Famotidine 40mg once daily

**Intervention Names:**

- Drug: Famotidine

**Label:** Famotidine 40mg once daily

**Type:** ACTIVE_COMPARATOR

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Lansoprazole 30mg once daily

**Description:** 30mg once daily

**Name:** Lansoprazole

**Type:** DRUG

#### Intervention 2

**Arm Group Labels:**

- Famotidine 40mg once daily

**Description:** 40mg once daily

**Name:** Famotidine

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Description:** 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.

**Measure:** Recurrent ulcer bleeding

**Time Frame:** 24 months

#### Secondary Outcomes

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

**Measure:** Recurrent ulcer detected by endoscopy at 24-month

**Time Frame:** at the 24th month of follow-up

### Eligibility Module

**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

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Locations

**Location 1:**

**City:** Hong Kong

**Country:** China

**Facility:** Endoscopy Center, Prince of Wales Hospital, Shatin

#### Overall Officials

**Official 1:**

**Affiliation:** Chinese University of Hong Kong

**Name:** Grace L Wong, MD

**Role:** PRINCIPAL_INVESTIGATOR

### IPD Sharing Statement Module

**IPD Sharing:** NO

### References Module

#### References

**Citation:** 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.

**PMID:** 31229990

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000010335

- Term: Pathologic Processes

- ID: D000004378

- Term: Duodenal Diseases

- ID: D000007410

- Term: Intestinal Diseases

- ID: D000005767

- Term: Gastrointestinal Diseases

- ID: D000004066

- Term: Digestive System Diseases

- ID: D000013272

- Term: Stomach Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: All

- Name: All Conditions

- Abbrev: BC06

- Name: Digestive System Diseases

### Condition Browse Module - Browse Leaves

- ID: M9556

- Name: Hemorrhage

- Relevance: HIGH

- As Found: Bleeding

- ID: M17206

- Name: Ulcer

- Relevance: HIGH

- As Found: Ulcer

- ID: M14850

- Name: Recurrence

- Relevance: LOW

- As Found: Unknown

- ID: M13348

- Name: Peptic Ulcer

- Relevance: HIGH

- As Found: Peptic Ulcer

- ID: M7552

- Name: Duodenal Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M10444

- Name: Intestinal Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M7255

- Name: Digestive System Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M8883

- Name: Gastrointestinal Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M16062

- Name: Stomach Diseases

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000010437

- Term: Peptic Ulcer

- ID: D000014456

- Term: Ulcer

- ID: D000006470

- Term: Hemorrhage

### Intervention Browse Module - Ancestors

- ID: D000000897

- Term: Anti-Ulcer Agents

- ID: D000005765

- Term: Gastrointestinal Agents

- ID: D000054328

- Term: Proton Pump Inhibitors

- ID: D000004791

- Term: Enzyme Inhibitors

- ID: D000045504

- Term: Molecular Mechanisms of Pharmacological Action

- ID: D000006635

- Term: Histamine H2 Antagonists

- ID: D000006633

- Term: Histamine Antagonists

- ID: D000018494

- Term: Histamine Agents

- ID: D000018377

- Term: Neurotransmitter Agents

- ID: D000045505

- Term: Physiological Effects of Drugs

### Intervention Browse Module - Browse Branches

- Abbrev: Gast

- Name: Gastrointestinal Agents

- Abbrev: All

- Name: All Drugs and Chemicals

### Intervention Browse Module - Browse Leaves

- ID: M18303

- Name: Famotidine

- Relevance: HIGH

- As Found: Mobile Health

- ID: M30379

- Name: Lansoprazole

- Relevance: HIGH

- As Found: Marginal

- ID: M30380

- Name: Dexlansoprazole

- Relevance: HIGH

- As Found: Marginal

- ID: M4188

- Name: Antacids

- Relevance: LOW

- As Found: Unknown

- ID: M4219

- Name: Anti-Ulcer Agents

- Relevance: LOW

- As Found: Unknown

- ID: M8881

- Name: Gastrointestinal Agents

- Relevance: LOW

- As Found: Unknown

- ID: M27630

- Name: Proton Pump Inhibitors

- Relevance: LOW

- As Found: Unknown

- ID: M7951

- Name: Enzyme Inhibitors

- Relevance: LOW

- As Found: Unknown

- ID: M9708

- Name: Histamine

- Relevance: LOW

- As Found: Unknown

- ID: M9711

- Name: Histamine H2 Antagonists

- Relevance: LOW

- As Found: Unknown

- ID: M212144

- Name: Histamine phosphate

- Relevance: LOW

- As Found: Unknown

- ID: M9709

- Name: Histamine Antagonists

- Relevance: LOW

- As Found: Unknown

- ID: M20504

- Name: Neurotransmitter Agents

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Meshes

- ID: D000064747

- Term: Lansoprazole

- ID: D000064748

- Term: Dexlansoprazole

- ID: D000015738

- Term: Famotidine

### Misc Info Module

- Version Holder: 2024-05-24
