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

When Should Low-dose Aspirin be Resumed After Peptic Ulcer Bleeding? A Randomized Controlled Trial

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.

Study Overview

• Status: Recruiting
• Conditions: Aspirin; GastroIntestinal Bleeding
• Intervention / Treatment: Other: Resume Aspirin within 12 hours; Other: Resume Aspirin 72 - 84 hours

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.

• Study Type: Interventional
• Enrollment (Anticipated): 436
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Ka Man Kee, MPH; Phone Number: 85235053855; Email: carmenkee@cuhk.edu.hk
• Study Contact Backup: Name: Jessica Ching, MPH; Phone Number: 85235053524; Email: jessicaching@cuhk.edu.hk

Study Locations

• Hong Kong
  • Hong Kong, Hong Kong
    • Recruiting
    • Prince of Wales Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Withold aspirin till after endoscopic haemostasis; Withhold the standard treatment of aspirin within 12 hours after endoscopic haemostasis.	Other: Resume Aspirin within 12 hours; Resume the standard treatment within 12 hours after endoscopic haemostasis
Active Comparator: Withold aspirin till 72 hours; Withhold the standard treatment of aspirin till 72 after endoscopic haemostasis.	Other: Resume Aspirin 72 - 84 hours; Resume the standard treatment between 72 and 84 hours after endoscopic haemostasis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recurrent peptic ulcer bleeding	Recurrent peptic ulcer bleeding within 30 days of endoscopic treatment	30 days after endoscopic treatment

Collaborators and Investigators

• Sponsor: Chinese University of Hong Kong
• Collaborators: National Taiwan University Hospital; Beijing Friendship Hospital
• Investigators: Principal Investigator: Siew C Ng, MD, Chinese University of Hong Kong

Study record dates

Study Major Dates

• Study Start (Actual): January 14, 2019
• Primary Completion (Anticipated): February 28, 2024
• Study Completion (Anticipated): February 28, 2024

Study Registration Dates

• First Submitted: December 20, 2018
• First Submitted That Met QC Criteria: December 20, 2018
• First Posted (Actual): December 24, 2018

Study Record Updates

• Last Update Posted (Actual): October 22, 2020
• Last Update Submitted That Met QC Criteria: October 20, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Stomach Diseases; Intestinal Diseases; Duodenal Diseases; Hemorrhage; Peptic Ulcer; Gastrointestinal Hemorrhage; Peptic Ulcer Hemorrhage; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Antipyretics; Aspirin
• Other Study ID Numbers: ReASA

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No