When Should Low-dose Aspirin be Resumed After Peptic Ulcer Bleeding?

NCT ID: NCT03785015

Last Updated: 2020-10-22

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 436 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-01-14
• Study Completion Date: 2024-02-28

Brief Summary

Acute upper gastrointestinal (GI) bleeding associated with the use of low-dose aspirin (ASA) is a major cause of peptic ulcer bleeding worldwide. Among survivors of acute myocardial infarction, a study of over 14,000 patients reported that the risk of life-threatening GI bleeding in the first two months is 7 times higher than that in the subsequent months. After endoscopic control of ulcer bleeding, most patients with cardiovascular (CV) diseases will need to resume ASA. However, the investigator found that immediate resumption of ASA saves life but at the expense of higher risk of recurrent bleeding. Peptic ulcer bleeding associated with ASA is a major cause of hospitalization in Hong Kong. Currently, ASA use has contributed to about one-third of the bleeding ulcers admitted to our hospital that serves a local population of 1.5 million. Accordingly, current international guidelines recommend early resumption of ASA but the optimal timing is unknown. Clinicians often face the dilemma: when should ASA be resumed? Furthermore, patients who suffer from acute peptic ulcer bleeding are often elderly patients with significant co-morbidities. Mortality in these patients remains high. Clinicians are facing an increasing number of patients who are on antiplatelet drugs or anticoagulants. The investigator proposes a open-label randomized-controlled trial to evaluate the optimal timing of resuming ASA in patients with CV diseases complicated by peptic ulcer bleeding. Patients will be randomized to resume the standard treatment within first few hours or only to resume the standard treatment 72 hours after endoscopic haemostasis.

Detailed Description

Acute upper gastrointestinal (GI) bleeding associated with the use of low-dose aspirin (ASA) is a major cause of peptic ulcer bleeding worldwide. Among survivors of acute myocardial infarction, a study of over 14,000 patients reported that the risk of life-threatening GI bleeding in the first two months is 7 times higher than that in the subsequent months (1). After endoscopic control of ulcer bleeding, most patients with cardiovascular (CV) diseases will need to resume ASA. Clinicians often face the dilemma: when should ASA be resumed? Furthermore, patients who suffer from acute peptic ulcer bleeding are often elderly patients with significant co-morbidities. Mortality in these patients remains high. Clinicians are facing an increasing number of patients who are on antiplatelet drugs or anticoagulants.

However, there are very limited data to guide the best timing for resumption of ASA in these high risk patients. To date, our group has conducted the only randomized controlled trial in the literature that has partially addressed this issue. Importantly, the investigator found that immediate resumption of ASA saves life but at the expense of higher risk of recurrent bleeding (2). Accordingly, current international guidelines recommend early resumption of ASA but the optimal timing is unknown.

In the setting of acute GI bleeding, it is often a dilemma whether to stop or to restart these drugs. The balance between bleeding and thrombotic risks is difficult and treatment is often empirical and not evidence-based.

The investigator aims to test the hypothesis that in ASA users complicated by peptic ulcer bleeding, withholding ASA till day 3 reduces the risk of recurrent bleeding compared to immediate resumption of ASA without a significant increase in mortality.

References

1. Moukarbel GV, Signorovitch JE, Pfeffer MA et al. Gastrointestinal bleeding in high risk survivors of myocardial infarction: the VALIANT Trial. Eur Heart J 2009;30(18):2226-32.

2. Sung JJ, Lau JY, Ching JY et al. Continuation of low-dose aspirin therapy in peptic ulcer bleeding: a randomized trial. Ann Intern Med 2010;152(1):1-9.

Conditions

Aspirin; GastroIntestinal Bleeding

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Withold aspirin till after endoscopic haemostasis

Withhold the standard treatment of aspirin within 12 hours after endoscopic haemostasis.

Group Type: EXPERIMENTAL

Resume Aspirin within 12 hours

Intervention Type: OTHER

Resume the standard treatment within 12 hours after endoscopic haemostasis

Withold aspirin till 72 hours

Withhold the standard treatment of aspirin till 72 after endoscopic haemostasis.

Group Type: ACTIVE_COMPARATOR

Resume Aspirin 72 - 84 hours

Intervention Type: OTHER

Resume the standard treatment between 72 and 84 hours after endoscopic haemostasis

Interventions

Resume Aspirin within 12 hours

Resume the standard treatment within 12 hours after endoscopic haemostasis

Intervention Type: OTHER

Resume Aspirin 72 - 84 hours

Resume the standard treatment between 72 and 84 hours after endoscopic haemostasis

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

1. Age >18

2. Patients with actively bleeding gastroduodenal lesions (peptic ulcer, bleeding erosions, or Dieulafoy's lesion) or ulcers showing other high risk stigmata (visible blood vessels or adherent clots) treated by endoscopic therapy

3. Subjects continue to require regular ASA or dual anti-platelet therapy for treatment of CV or cerebrovascular diseases after this bleeding episode

Exclusion Criteria

1. Patients who received ASA for primary prophylaxis

2. Unsuccessful endoscopic hemostasis of bleeding ulcers or ulcer perforation

3. Gastric outlet obstruction

4. Known sensitivity to PPIs

5. Previous partial gastrectomy or vagotomy

6. Patients need concomitant anticoagulant

7. Pregnant unless sterilization, menopause or last menstrual period within 7 days

8. Other co-morbidities or advanced age that will hinder the drug compliance or follow up

9. Malignancy on active treatment

10. Unable to give consent

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Beijing Friendship Hospital

OTHER

Sponsor Role: collaborator

National Taiwan University Hospital

OTHER

Sponsor Role: collaborator

Chinese University of Hong Kong

OTHER

Sponsor Role: lead

Responsible Party

Siew Chien NG

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Siew C Ng, MD

Role: PRINCIPAL_INVESTIGATOR

Chinese University of Hong Kong

Locations

Prince of Wales Hospital

Hong Kong, , Hong Kong

Site Status: RECRUITING

Countries

Hong Kong

Central Contacts

Ka Man Kee, MPH

Role: CONTACT

carmenkee@cuhk.edu.hk

85235053855

Jessica Ching, MPH

Role: CONTACT

jessicaching@cuhk.edu.hk

85235053524

Facility Contacts

Siew Chien Ng, PhD

Role: primary

siewchienng@cuhk.edu.hk

35053996

Other Identifiers

ReASA

Identifier Type: -

Identifier Source: org_study_id