Study of the Risk Factors and Outcomes After Gastrointestinal Bleeding

Study of Risk Factors for Gastrointestinal Bleeding and of the Determinants of Non-fatal and Fatal Cardiovascular Events After Gastrointestinal Bleeding in Patients Receiving Antithrombotic Therapy for Cardiovascular Prevention

The purpose of this multicenter, two component observational and standardized case-control study is to evaluate risk factors of gastrointestinal (GI) bleeding with a prospective 3-month and 12-month follow-up to examine outcomes and their possible causes.

Study Overview

• Status: Completed
• Conditions: Cardiovascular Diseases; Gastrointestinal Hemorrhage

Detailed Description

Antithrombotic therapies are effective for prevention of cardiovascular (CV) events but cause bleeding. Emerging evidence indicates that extra-cranial bleeding is just as important as myocardial infarction as a marker of risk for subsequent non-fatal and fatal CV events, but this issue has not been prospectively studied. If the association between bleeding and CV events is causal, prevention of bleeding, by targeting the risk factors, and prevention of the complications of bleeding, by targeting the causal pathways, could substantially reduce the burden of bleeding-related CV events. Progress in developing these approaches has been limited by a knowledge gap. Known risk factors do not fully explain bleeding risk and the investigators do not understand the mechanisms linking bleeding with adverse outcome and whether the association is causal.

One-half of bleeds that lead to CV events in patients receiving antithrombotic therapy arise in the GI tract. INTERBLEED plans to explore risk factors for GI bleeding, and outcomes after GI bleeding, in this well-circumscribed and important group using a case-control design with prospective 3 month and 12 month follow-up.

Specific objectives are to: (1) identify risk factors for GI bleeding and estimate their population attributable risk; (2) determine the risk of non-fatal and fatal CV events and functional outcomes after GI bleeding; and (3) explore the possible mechanisms linking GI bleeding with CV outcome.

INTERBLEED will recruit 2500 case-control pairs from centres in Argentina, Belgium, Brazil, China, Ireland and the Netherlands. Data will be collected on patient characteristics, medical history and, in cases, the work-up, management and outcomes after bleeding. The INTERBLEED results will help to develop new approaches to reducing the burden of bleeding-related CV events.

• Study Type: Observational
• Enrollment (Actual): 4745

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Hamilton, Ontario, Canada
      • Hamilton Health Sciences, PHRI

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

The community, inpatient/outpatient clinics (endoscopy clinics, stroke prevention clinics, cardiac/vascular clinics), emergency rooms

Description

Inclusion Criteria:

Cases

• Age ≥ 18 years at enrollment
• Written informed consent
• Confirmed cardiovascular disease
• Present to the hospital with GI tract bleed or develop GI tract bleed in hospital

Controls

• Age ≥ 18 years at enrollment
• Written informed consent
• Confirmed cardiovascular disease

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Myocardial infarction, stroke or death	Up to one year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in functional status from baseline to 3 months	Functional status measured by SAGE questionnaire	3 months
Change in functional status from baseline to 12 months	Functional status measured by SAGE questionnaire	12 months

Collaborators and Investigators

• Sponsor: Population Health Research Institute
• Collaborators: Bristol-Myers Squibb; Heart and Stroke Foundation of Ontario; Daiichi Sankyo
• Investigators: Principal Investigator: John Eikelboom, MD, Population Health Research Institute, McMaster University

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2015
• Primary Completion (Actual): December 15, 2023
• Study Completion (Actual): December 1, 2024

Study Registration Dates

• First Submitted: July 29, 2015
• First Submitted That Met QC Criteria: July 31, 2015
• First Posted (Estimated): August 3, 2015

Study Record Updates

• Last Update Posted (Actual): July 31, 2025
• Last Update Submitted That Met QC Criteria: July 28, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Digestive System Diseases; Gastrointestinal Diseases; Cardiovascular Diseases; Hemorrhage; Gastrointestinal Hemorrhage
• Other Study ID Numbers: INTERBLEED