MidregiOnal Proatrial Natriuretic Peptide to Guide SEcondary Stroke Prevention

Study Overview
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Brief Summary
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The present trial is addressing the question if a biologically distinct subgroup of ischemic stroke patients without known atrial fibrillation at admission, selected by a cut-off level of MRproANP concentration, which represents a underlying increased risk of cardiac thrombogenicity, benefits from direct oral anticoagulation (DOAC) within 7 days of symptom onset versus standard of care (antiplatelet) as preventive treatment.

Detailed Description
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Three DOACs with marketing authorisation in Switzerland and the EU for the prevention of stroke and systemic embolism in patients with atrial fibrillation can be used. Eligible patients will be randomly assigned to either the standard of care (control) or the experimental (direct start with DOAC) arm with a ratio of 1:1. Each study participant will be observed during a follow up period within one year after index stroke.

Official Title
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MidregiOnal Proatrial Natriuretic Peptide to Guide SEcondary Stroke Prevention: The MOSES-study. An International, Multicentre, Randomised-controlled, Two-arm, Assessor-blinded Trial

Conditions
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Stroke, Ischemic

Intervention / Treatment
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* Drug: Dabigatran
* Drug: Apixaban
* Drug: Edoxaban
* Drug: Aspirin
* Drug: Clopidogrel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical diagnosis of ischemic stroke level ≥200pmol/L within 72 hours from symptom onset Age ≥ 18 years Signed informed consent Exclusion Criteria: History of AF, AF on 12-lead ECG on admission or any AF ≥30 seconds during heart-rhythm monitoring prior to randomization Other condition that require anticoagulant therapy (e.g., venous thromboembolism) as per Investigator's judgment including therapeutical dose of low-molecular-weight heparin or heparin Strong likelihood to be treated with prolonged (i.e. more than 30 days) dual antiplatelet therapy during the course of the trial (such as coronary stenting, etc.) Patients undergoing planned procedures where therapy with a DOAC is a contraindication (e.g. surgery) Previous intracranial hemorrhage in the last year Evidence of severe cerebral amyloid angiopathy if MRI scan performed Chronic kidney disease with creatinin clearance <30ml/min and or subject who requires haemodialysis or peritoneal dialysis Known bleeding diathesis (e.g. active peptic ulcer disease , platelet count < 100'000/mm3 or haemoglobin < 9 g/dl or INR ≥ 1.7, documented haemorrhagic tendencies or blood dyscrasias) Active infective endocarditis CT or MRI evidence of cerebral vasculitis Known allergy or intolerance to antiplatelets or DOACs Female who is pregnant or lactating or has a positive pregnancy test at time of admission Current participation in another drug trial

Ages Eligible for Study
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Minimum Age: 18 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: DOACs<br>Direct oral anticoagulants | Drug: Dabigatran<br>* 150mg 2x/d<br>* Other names: Pradaxa;Drug: Apixaban<br>* 5mg 2x/d<br>* Other names: Eliquis;Drug: Edoxaban<br>* 60mg 1x/d<br>* Other names: Lixiana;|
| Active Comparator: Antiplatelets<br>SOC therapy with antiplatelets until study completion or until detection of AF. After detection of AF treatment with DOAC becomes SOC. | Drug: Aspirin<br>* 100mg 1x/d<br>* Other names: Aspirin cardio;Drug: Clopidogrel<br>* 75mg 1x/d<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recurrent stroke of any type | The primary outcome measure is the time to any recurrent stroke (ischemic, hemorrhagic, unspecified, or fatal stroke) | within one year after index stroke | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite of major bleeding, recurrent stroke and/or vascular death | Composite of major bleeding, recurrent stroke and/or vascular death (whichever occurs first) | within one year after index stroke | 
| Major bleeding, recurrent stroke and/or vascular death as single components | Each single component of the composite in outcome 2 (major bleeding, recurrent stroke and/or vascular death) | within one year after index stroke |