Clinical trial NCT01274767: Prevention of Recurrent Ulcer Bleeding in High-risk Aspirin Users Who Are Not Infected With Helicobacter Pylori
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 type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Ulcer Bleeding
Lead sponsor: Chinese University of Hong Kong
Sponsor class: OTHER
First posted: 2011-01-12
Enrollment: 467
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: High-risk patients were from our hospital while average-risk patients were from our out-patient clinics.

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.

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.

Eligibility 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

Primary outcomes:
measure: Ulcer complications
timeFrame: 10 years
Secondary outcomes:
Other outcomes:
Locations:
city: Hong Kong
country: China
facility: Prince of Wales Hospital
Study officials:
affiliation: Chinese University of Hong Kong
name: Francis KL CHAN, MD
role: PRINCIPAL_INVESTIGATOR
References: