Administration of low risk oral anticoagulation agents to patients with pre-stage atrial fibrillation for stroke prophylaxis

Phase 1

Conditions: Atrial fibrillation (AF) is one cause of stroke. Stroke rate is increased in patients with atrial high rate episodes (AHRE, an early stage of AF) as well, even if stroke rates are lower when compared to stroke rates in patients with diagnosed AF. Prevention of stroke, systemic embolism or cardiovascular death in patients with AHRE but without diagnosed atrial fibrillation (AF) and in addition at least two stroke risk factors by intake of NOACs shall be investigated.
MedDRA version: 23.1Level: LLTClassification code 10003656Term: Atrial arrhythmiaSystem Organ Class: 100000004849
Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

Registration Number: EUCTR2015-003997-33-IT

Lead Sponsor: KOMPETENZNETZVORHOFFLIMMERN E.V. (AFNET E.V.), COMPETENCE NETWORK ATRIAL FIBRILLATIO

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 2534

Inclusion Criteria

- Pacemaker, defibrillator or insertable cardiac monitor implanted for any reason with feature of detection of AHRE, implanted at least 2 months prior to randomisation.
- AHRE detection feature activated for adequate detection of AHRE
- AHRE (= 170 bpm atrial rate and = 6 min duration) documented by the implanted device.
Any AHRE episode recorded is potentially eligible, but AHRE episodes detected in the first 2 months after implantation of a new device involving placement or repositioning of atrial electrodes are not eligible.
AHRE episodes recorded in the first two months after a simple box change operation, i.e. exchange of a pacemaker or defibrillator device without exchange or repositioning of atrial electrodes, are eligible.
- Age = 65 years
- In addition, at least one of the following cardiovascular conditions leading to a modified CHA2DS2VASc score of 2 or more: Age = 75 years, heart failure (clinically overt or LVEF < 45%), arterial hypertension (chronic treatment for hypertension, estimated need for continuous antihypertensive therapy or resting blood pressure > 145/90 mmHg), diabetes mellitus, prior stroke or transient ischemic attack (TIA), vascular disease (previous myocardial infarction, peripheral, carotid/cerebral, or aortic plaques on transesophageal echocardiogram [TEE]).
- Provision of signed informed consent
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 2543

Exclusion Criteria

- Any disease that limits life expectancy to less than 1 year.
- Participation in another controlled clinical trial, either within the past two months or still ongoing.
- Previous participation in the present trial NOAH - AFNET 6.
- Drug abuse or clinically manifest alcohol abuse.
- Any history of overt AF or atrial flutter.
- Indication for oral anticoagulation (e.g. deep venous thrombosis).
- Contraindication for oral anticoagulation in general.
- Contraindication for edoxaban as stated in the current SmPC.
-Indication for long-term antiplatelet therapy other than acetylsalicylic acid or a need for treatment with any antiplatelet agent in addition to edoxaban, especially dual antiplatelet therapy (DAPT). Patients with a transient requirement for DAPT (e.g. after receiving a stent) will be eligible when the need for DAPT is no longer present.
- Acute coronary syndrome, coronary revascularisation (PCI or bypass surgery), or overt stroke within 30 days prior to randomisation.
- End stage renal disease (creatinine clearance (CrCl) < 15 ml/min as calculated by the Cockcroft-Gault method)
Legal exclusion criterion (applicable in countries where legally required)
- All persons exempt from participation in a clinical trial by law.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To demonstrate that oral anticoagulation with the NOAC edoxaban is superior to current therapy (antiplatelet therapy or no therapy depending on cardio-vascular risk) to prevent stroke, systemic embolism, or cardiovascular death in patients with AHRE but without overt AF and at least two stroke risk factors leading to a modified CHA2DS2VASc score of 2 or more.;Secondary Objective: n/a;Primary end point(s): Time from randomisation to the first occurrence of stroke, systemic embolism, or cardiovascular death. A detailed definition of these outcome events is provided in Appendix III of the study protocol.;Timepoint(s) of evaluation of this end point: Evaluation of stroke, systemic embolism, or cardiovascular death by CRO: within 24 hours after SAE reporting by the investigator.<br>Evaluation of stroke, systemic embolism, or cardiovascular death by an Critical Event Committee (CEC) during the course of the trial on a regular basis (monthly).

Secondary Outcome Measures

Name	Time	Method