Non-warfarin Oral AntiCoagulant Resumption After Gastrointestinal Bleeding in Atrial Fibrillation Patients

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Upper Gastrointestinal Bleeding

Intervention / Treatment
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* Other: restart NOAC very early
* Other: restart NOAC early


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: restart NOAC very early<br>restart NOAC within 24 hours | Other: restart NOAC very early<br>* withhold NOAC less than 24 hours Post OGD<br>|
| Active Comparator: restart NOAC early<br>restart NOAC at 72 - 84 hours | Other: restart NOAC early<br>* withhold NOAC for 72 to 84 hours Post OGD<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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gastrointestinal bleeding, stroke, thromboembolism, atrial fibrillation, NOAC