Prevention of Recurrent Ulcer Bleeding in High-risk Aspirin Users Who Are Not Infected With Helicobacter Pylori (3NANC)

Study Description

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Brief Summary:

Low-dose aspirin is the mainstay of treatment for patients with coronary heart disease and stroke. However, low-dose aspirin increases the risk of ulcer bleeding. Current evidence indicates that 80 - 100 mg of aspirin daily provides good protection against vascular events and the risk of ulcer bleeding is low (about 1% per year). Since the overall risk of bleeding is low, aspirin users who do not have previous ulcer disease do not require prophylaxis with anti-ulcer drugs. In contrast, aspirin users with a history of ulcer disease have a 2- to 4-fold increased risk of ulcer bleeding. The best strategy for reducing the risk of bleeding in high-risk aspirin users remains unclear. Current strategies for high-risk patients include the use of anti-ulcer drugs, elimination of risk factors (e.g. Helicobacter pylori), or the use of enteric-coated aspirin.

Although co-therapy of aspirin with an acid suppressant reduces the risk of ulcer bleeding, drug compliance may limit its clinical usefulness particularly in patients who are already receiving multiple drugs. The efficacy of enteric-coated aspirin in preventing ulcer complications showed conflicting results. One study found that enteric-coated aspirin increases the risk of ulcer bleeding. A recent study showed that enteric-coated aspirin causes minimal acute gastric injury.

The investigators postulated that among patients without H. pylori infection and a history of ulcer bleeding who continue to use low-dose aspirin, enteric-coated aspirin reduces the long-term risk of ulcer complications to a level that is comparable to that of average-risk aspirin users.

Condition or disease
Ulcer Bleeding

Detailed Description:

Low-dose aspirin is increasingly used for the prophylaxis against coronary heart disease and stroke. However, it is also an important cause of peptic ulcer bleeding worldwide. In England and Wales, low-dose aspirin is estimated to account for about 10% of ulcer bleeding in people aged 60 and over [Weil 1995]. The problem of aspirin-related ulcer disease is expanding with the increasing use of aspirin for cardiovascular prophylaxis.

No dose of aspirin is entirely free of risk. Using a daily dose of aspirin as low as 75 mg, the risk of ulcer bleeding doubles that of non-users [Weil 1995]. Previous ulcer disease and concurrent major medical illnesses are important risk factors for ulcer bleeding with low-dose aspirin. Among aspirin users, those with previous ulcer disease have a 5-fold increased risk of ulcer bleeding [Lanas 2000].

Various strategies have been used to prevent recurrent ulcer bleeding in high-risk aspirin users, such as eradication of Helicobacter pylori, the use of prophylactic anti-ulcer drugs or enteric-coated aspirin. Recently, the investigators have shown that the eradication of H. pylori is comparable to maintenance treatment with omeprazole, a potent acid suppressant, in preventing recurrent ulcer bleeding for high-risk aspirin users [Chan 2001]. However, about 50% of aspirin users are not infected with H. pylori.

The optimal strategy to prevent ulcer complications for high-risk aspirin users who are not infected with H. pylori remains undefined. Although co-therapy of aspirin with an acid suppressant reduces the risk of ulcer bleeding, drug compliance may limit its clinical usefulness particularly in patients who are already receiving multiple drugs.

Study Design

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Study Type :	Observational
Actual Enrollment :	467 participants
Observational Model:	Cohort
Time Perspective:	Prospective
Official Title:	Prevention of Recurrent Ulcer Bleeding in High-risk Aspirin Users Who Are Not Infected With Helicobacter Pylori: A Prospective Cohort Study (NSAID#3NANC Study)
Study Start Date :	January 1995
Actual Primary Completion Date :	June 2010
Actual Study Completion Date :	September 2010

Groups and Cohorts

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Group/Cohort
High risk cohort; Patients having history of endoscopically confirmed ulcer bleeding, need long-term aspirin for cardiovascular or cerebrovascular prophylaxis and have a negative test for H. pylori based on histology
Average risk cohort; Patients having no history of endoscopically confirmed ulcer bleeding, need long-term aspirin for cardiovascular or cerebrovascular prophylaxis and have H. pylori positive OR negative

Outcome Measures

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Primary Outcome Measures :

1. Ulcer complications [ Time Frame: 10 years ]
   defined as bleeding or perforation

Eligibility Criteria

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No
Sampling Method:	Non-Probability Sample

Study Population

High-risk patients were from our hospital while average-risk patients were from our out-patient clinics.

Criteria

High risk cohort:

Inclusion Criteria:

1. History of endoscopically confirmed ulcer bleeding
2. Need long-term aspirin for cardiovascular or cerebrovascular prophylaxis
3. A negative test for H. pylori based on histology

Exclusion Criteria:

1. Concomitant use of anti-ulcer drug, anticoagulant, non-aspirin NSAIDs or steroids
2. Current or past H. pylori infection
3. Previous acid-reduction gastric surgery
4. Gastric outlet obstruction, erosive esophagitis, gastroesophageal varices
5. Moribund or incurable cancers

Average-risk cohort

Inclusion criteria:

Patients must fulfill ALL of the following:

1. No history of ulcer bleeding
2. Need long-term aspirin for cardiovascular or cerebrovascular prophylaxis
3. H. pylori positive OR negative

Exclusion criteria:

1. Concomitant use of anti-ulcer drug, anticoagulant, non-aspirin NSAIDs or steroid
2. Previous acid-reduction gastric surgery
3. Moribund or incurable cancers
4. Previous attempts of H. pylori eradication

Contacts and Locations

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Locations

China
Prince of Wales Hospital
Hong Kong, China

Sponsors and Collaborators

Chinese University of Hong Kong

Investigators

Principal Investigator:	Francis KL CHAN, MD	Chinese University of Hong Kong

More Information

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party:	Francis KL Chan, Professor, Chinese University of Hong Kong
ClinicalTrials.gov Identifier:	NCT01274767 History of Changes
Other Study ID Numbers:	3NANC
First Posted:	January 12, 2011
Last Update Posted:	April 24, 2017
Last Verified:	April 2017

Additional relevant MeSH terms:

Ulcer; Hemorrhage; Pathologic Processes; Aspirin; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs	Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Molecular Mechanisms of Pharmacological Action; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Enzyme Inhibitors; Antipyretics