Non-warfarin Oral AntiCoagulant Resumption After Gastrointestinal Bleeding in Atrial Fibrillation Patients (NOAC-GAP)

Non-warfarin Oral AntiCoagulant Resumption After Gastrointestinal Bleeding in Atrial Fibrillation Patients (NOAC-GAP) - a Randomised Controlled Study

Current clinical society guidelines and statements are non-specific and relatively open-ended regarding the optimal timing to restart non-warfarin oral anticoagulant (NOAC) after gastrointestinal bleeding (GIB) in patients with atrial fibrillation (AF) who require the prophylactic medication for stroke prevention. These patients are at increased risk for devastating future thromboembolic events including stroke if NOAC is not resumed promptly, whilst premature resumption of anticoagulants can result in recurrent GIB, haemorrhage, anaemia, myocardial ischaemia and infarction in those with ischaemic heart disease, and even death. However, the question as to how early a NOAC can be safely restarted after acute GIB has not been previously answered, and there remains an important knowledge gap.

Study Overview

• Status: Recruiting
• Conditions: Upper Gastrointestinal Bleeding
• Intervention / Treatment: Other: restart NOAC very early; Other: restart NOAC early

Detailed Description

The effectiveness and relative safety of NOACs have been demonstrated in large international studies where reductions in the incidence of stroke in patients with AF have been reported. However, the benefits of an anticoagulant are offset by increased incident rates of bleeding including gastrointestinal bleeding (GIB) and, less commonly, intracranial bleeding, warranting careful anticoagulation management during periods when patients are susceptible to the risks for bleeding, stroke and thromboembolism.

The exact duration for withholding NOAC after acute GIB is unknown and in general, current clinical society guidelines and statements are non-specific and relatively open-ended regarding the optimal timing to restart non-warfarin oral anticoagulant (NOAC) after gastrointestinal bleeding (GIB) in patients with atrial fibrillation (AF) who require the prophylactic medication for stroke prevention. These patients are at increased risk for devastating future thromboembolic events including stroke if NOAC is not resumed, whilst premature resumption of anticoagulants can result in recurrent GIB, haemorrhage, anaemia, myocardial ischaemia and infarction in those with ischaemic heart disease, and even death.

The purpose of this study is to determine if restarting NOAC very early after endoscopic haemostasis of bleeding peptic ulcer lesions is equivalent to early resumption in AF patients in terms of safety and efficacy for prevention of recurrent bleeding freedom from GIB recurrence, while maintaining undiminished benefits in reducing incident rates of systemic thromboembolism.

• Study Type: Interventional
• Enrollment (Anticipated): 552
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Bing Yee SUEN, BSN; Phone Number: +852 3505 2640; Email: suenbingyee@cuhk.edu.hk
• Study Contact Backup: Name: Ming Yeung HO, BSc; Phone Number: +852 2637 1398; Email: andrewho@cuhk.edu.hk

Study Locations

• Australia
  • New South Wales
    • Blacktown, New South Wales, Australia
      • Recruiting
      • Blacktown Hospital
      • Contact: Raymond KWOK, MD
• Hong Kong
  • Hong Kong, Hong Kong
    • Recruiting
    • Endoscopy Center, Prince of Wales Hospital
    • Contact: Bing Yee SUEN, BSN; Phone Number: +852 3505 2640; Email: suenbingyee@cuhk.edu.hk
    • Contact: Joseph SUNG, MD; Phone Number: +852 3505 3132; Email: jjysung@cuhk.edu.hk
    • Principal Investigator: Joseph SUNG, MD
    • Principal Investigator: Erik FUNG, MD
• Singapore
  • Singapore, Singapore
    • Recruiting
    • National University Hospital
    • Contact: Jimmy SO

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age ≥18 years
• History of AF
• Taking any kind of NOAC at the time of index acute GIB
• Acute upper GIB (non-variceal bleeding lesions accounting for the GIB) with or without endoscopic treatment confirmed endoscopic haemostasis verified by GI specialist
• Patient or next-of-kin able to provide informed consent

Exclusion Criteria:

• Concomitant stroke (including TIA) at the time of index GIB
• Requiring bridging IV heparin therapy
• Portal hypertension
• Known bleeding diathesis

• Other conditions precluding use of NOAC at the time of randomisation

  • Pregnancy
  • Tumour bleeding
  • Antidote administration to reverse anticoagulation effect of NOACs

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: restart NOAC very early; restart NOAC within 24 hours	Other: restart NOAC very early; withhold NOAC less than 24 hours Post OGD
Active Comparator: restart NOAC early; restart NOAC at 72 - 84 hours	Other: restart NOAC early; withhold NOAC for 72 to 84 hours Post OGD

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
recurrent gastrointestinal bleeding	melaena and/or haematemesis with drop in Hb >2g/dL and confirmation of bleeding by endoscopy.	30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
recurrent gastrointestinal bleeding	melaena and/or haematemesis with drop in Hb >2g/dL and confirmation of bleeding by endoscopy.	90 days
Ischemic stroke or transient ischaemic attack	an acute episode of neurologic deficit of presumed vascular or cardioembolic origin; its presence will be confirmed by a member of the neurology service	30 days
Systemic thromboembolism	any clinical and/or radiographic acute stroke and/or an acute peripheral arterial thromboembolic event including acute limb ischaemia, coronary embolism and arterial thromboembolism	30 days
Death	All-cause mortality	6 months

Collaborators and Investigators

• Sponsor: Chinese University of Hong Kong
• Investigators: Principal Investigator: Joseph SUNG, MD, CUHK

Study record dates

Study Major Dates

• Study Start (Actual): March 11, 2019
• Primary Completion (Anticipated): June 30, 2024
• Study Completion (Anticipated): December 30, 2025

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): May 5, 2020
• Last Update Submitted That Met QC Criteria: May 4, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Keywords: stroke; NOAC; atrial fibrillation; thromboembolism; gastrointestinal bleeding
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Gastrointestinal Diseases; Arrhythmias, Cardiac; Atrial Fibrillation; Hemorrhage; Gastrointestinal Hemorrhage
• Other Study ID Numbers: NOAC-GAP

Drug and device information, study documents

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