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H2RA VS PPI for the Prevention of Ulcer Bleeding Associated With Low-dose Aspirin in Patients With Very High Ulcer Risk

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by Chinese University of Hong Kong
Sponsor:
Information provided by (Responsible Party):
Francis KL Chan, Chinese University of Hong Kong
ClinicalTrials.gov Identifier:
NCT01408186
First received: August 2, 2011
Last updated: February 19, 2014
Last verified: February 2014
  Purpose

Peptic ulcer bleeding associated with ASA or NSAIDs is a major cause of hospitalization in Hong Kong. The investigators previously showed that ASA or NSAIDs accounted for about half of all cases of hospitalizations for peptic ulcer bleeding. Currently, ASA use has contributed to about one-third of the bleeding ulcers admitted to the investigators hospital that serves a local population of 1.5 million.

In patients with acute coronary syndrome or acute ischemic stroke who develop ASA-induced bleeding peptic ulcers, whether ASA should be discontinued before ulcers have healed is a major dilemma. In another double-blind randomized trial, the investigators have shown that discontinuation of ASA after endoscopic treatment of bleeding ulcers was associated with a significantly increased in mortality within 8 weeks.

In the absence of safer aspirins, co-therapy with a gastroprotective drug remains the dominant preventive strategy. Given the vast number of people taking ASA, however, it is only cost-effective to identify and treat those who are at high risk of ulcer bleeding and who have a strong indication for ASA use. Data from observational studies and randomized trials have consistently shown that PPIs are effective in reducing the risk of ulcer bleeding associated with ASA. Other potential preventive strategies include eradication of H. pylori infection, substitution of ASA for other non-aspirin anti-platelet drugs, and co-therapy with misoprostol or H2RAs.


Condition Intervention Phase
Peptic Ulcer Bleeding
Drug: Rabeprazole
Drug: Famotidine
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Histamine-2 Receptor Antagonist Versus Proton-Pump Inhibitor for the Prevention of Ulcer Bleeding Associated With Low-dose Aspirin in Patients With Very High Ulcer Risk (ASP (PPI_H2RA) Study)

Resource links provided by NLM:


Further study details as provided by Chinese University of Hong Kong:

Primary Outcome Measures:
  • Recurrent ulcer bleeding [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Hematemesis or melena with ulcers or bleeding erosions confirmed by endoscopy, or a decrease in hemoglobin of at least 2 g/dL in the presence of endoscopically proven ulcers or multiple erosions. Bleeding erosions are defined as flat mucosal breaks of any size in the presence of blood/coffee ground in patients with hematemesis or melena, or >=10 erosions in patients with >=2 g/dL decrease in hemoglobin.


Secondary Outcome Measures:
  • Lower GI bleeding [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Lower gastrointestinal bleeding is defined by either melena or rectal bleeding causing hospital admission or transfusion, with negative results on upper endoscopy, or by a decrease in hemoglobin of at least 2 g/dL in association with negative results on upper endoscopy and no other explanations for the anemia.

  • serious cardiothrombotic events [ Time Frame: 12 Months ] [ Designated as safety issue: No ]
    Serious cardiothrombotic events


Estimated Enrollment: 332
Study Start Date: January 2011
Estimated Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Rabeprazole
Tablet 20mg daily for 12 months
Drug: Rabeprazole
Rabeprazole 20 mg daily
Other Name: Pariet
Active Comparator: Famotidine
Tablet 40mg daily for 12 months
Drug: Famotidine
Famotidine 40mg daily
Other Name: Pepcidine

Detailed Description:

No dose of "low-dose" aspirin (ASA) is safe in terms of the risk if ulcer bleeding. Even at a dose as low as 75 mg daily, ASA doubles the risk of ulcer bleeding when compared to the risk in non-users. This rise in the incidence was associated with a 44% increase in usage of ASA. In Hong Kong, ASA is also a major cause of peptic ulcer complications.

In the absence of safer aspirins, co-therapy with a gastroprotective drug remains the dominant preventive strategy. Given the vast number of people taking ASA, however, it is only cost-effective to identify and treat those who are at high risk of ulcer bleeding and who have a strong indication for ASA use. Data from observational studies and randomized trials have consistently shown that PPIs are effective in reducing the risk of ulcer bleeding associated with ASA. Other potential preventive strategies include eradication of H. pylori infection, substitution of ASA for other non-aspirin anti-platelet drugs, and co-therapy with misoprostol or H2RAs. Among these preventive strategies, co-therapy with a PPI for prevention of ulcer bleeding in high-risk ASA users remains the most studied and best proven strategy.

H2-receptor antagonists (H2RAs) are relatively weak acid suppressing drugs when compared to PPIs. Very few studies have evaluated the efficacy of H2RAs in the prevention of peptic ulcer bleeding with ASA. Two case-control studies yielded conflicting results with regard to the efficacy of H2RAs in reducing the risk of hospitalizations for ulcer bleeding with ASA. There is a limited data on the efficacy of H2RAs, however, our local health authority has endorsed the use of H2RA as a co-therapy in high-risk ASA users since 2001.

On the other hand, H2RAs have two potential advantages over PPIs. First, generic H2RAs are much cheaper than generic PPIs in Hong Kong. Second, unlike the interaction between PPIs and clopidogrel, concomitant use of H2RAs and clopidogrel is not associated with an increased risk of recurrent myocardial infarction. Thus, H2RA might be a cheap and safe gastroprotective drug in patients requiring dual anti-platelet therapy (i.e., ASA and clopidogrel) who require coronary stents.

In patients with acute coronary syndrome or acute ischemic stroke who develop ASA-induced bleeding peptic ulcers, whether ASA should be discontinued before ulcers have healed is a major dilemma. In another double-blind randomized trial, we have shown that discontinuation of ASA after endoscopic treatment of bleeding ulcers was associated with a significantly increased in mortality within 8 weeks.

The investigators aim to test the hypothesis that PPI is superior to H2RA for the prevention of recurrent ulcer bleeding in ASA users with a history ulcer bleeding.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. A history of documented peptic ulcer bleeding (self-reported history without confirmation by the clinician is not acceptable)
  2. Negative tests for H. pylori or successful eradication of H. pylori based on urease test and histology
  3. Expected regular use of ASA for the duration of the trial
  4. Age ≥ 18
  5. Written informed consent obtained

Exclusion Criteria:

  1. A history of gastric or duodenal surgery other than patch repair
  2. Severe erosive esophagitis (LA grade C or D)
  3. Gastric outlet obstruction
  4. Terminal illness
  5. Active malignancies
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01408186

Contacts
Contact: Jessica YL Ching, MPH +852 2632 3524 jessicaching@cuhk.edu.hk

Locations
China
Prince of Wales Hospital Recruiting
Hong Kong, China
Principal Investigator: Francis KL CHAN, MD         
Sponsors and Collaborators
Chinese University of Hong Kong
Investigators
Principal Investigator: Francis KL Chan, MD Chinese University of Hong Kong
  More Information

No publications provided

Responsible Party: Francis KL Chan, Professor, Chinese University of Hong Kong
ClinicalTrials.gov Identifier: NCT01408186     History of Changes
Other Study ID Numbers: APH Study
Study First Received: August 2, 2011
Last Updated: February 19, 2014
Health Authority: Hong Kong: Department of Health

Additional relevant MeSH terms:
Hemorrhage
Peptic Ulcer
Peptic Ulcer Hemorrhage
Ulcer
Digestive System Diseases
Duodenal Diseases
Gastrointestinal Diseases
Gastrointestinal Hemorrhage
Intestinal Diseases
Pathologic Processes
Stomach Diseases
Famotidine
Histamine H2 Antagonists
Rabeprazole
Anti-Ulcer Agents
Enzyme Inhibitors
Gastrointestinal Agents
Histamine Agents
Histamine Antagonists
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Pharmacologic Actions
Physiological Effects of Drugs
Proton Pump Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on November 24, 2014