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

This study has been completed.
Sponsor:
Information provided by:
Chinese University of Hong Kong
ClinicalTrials.gov Identifier:
NCT01274767
First received: January 11, 2011
Last updated: January 18, 2011
Last verified: January 2011
History of Changes
  Purpose

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
Ulcer Hemorrhage

Study Type: Observational
Study Design: 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)

Resource links provided by NLM:

MedlinePlus related topics: Bleeding
Drug Information available for: Aspirin
U.S. FDA Resources

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

Primary Outcome Measures:
  • Ulcer complications, defined as bleeding or perforation [ Time Frame: 10 years ] [ Designated as safety issue: No ]
Enrollment: 467
Study Start Date: January 1995
Study Completion Date: September 2010
Primary Completion Date: June 2010 (Final data collection date for primary outcome measure)
Groups/Cohorts
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

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.

References Weil J, Colin-Jones D, Langman M, et al. Prophylactic aspirin and risk of peptic ulcer bleeding. Br Med J 1005;310:827-30.

Lanas A, Bajador E, Serrano P, et al. Nitrovasodilators, low-dose aspirin, other nonsteroidal antiinflammatory drugs, and the risk of upper gastrointestinal bleeding. N Engl J Med 2000;343:834-9.

Chan FKL, Chung SCS, Suen BY, et al. Preventing recurrent upper gastrointestinal bleeding in patients with Helicobacter pylori infection who are taking low-dose aspirin or naproxen. N Engl J Med 2001;344:967-73.

  Eligibility
Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
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: NCT01274767

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

No publications provided

Responsible Party: Francis Ka Leung CHAN, Chinese University of Hong Kong
ClinicalTrials.gov Identifier: NCT01274767     History of Changes
Other Study ID Numbers: 3NANC
Study First Received: January 11, 2011
Last Updated: January 18, 2011
Health Authority: Department of Health,Hong Kong: China

ClinicalTrials.gov processed this record on March 01, 2015