- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02618577
Non-vitamin K Antagonist Oral Anticoagulants in Patients With Atrial High Rate Episodes (NOAH)
Non-vitamin K Antagonist Oral Anticoagulants in Patients With Atrial High Rate Episodes - An Investigator-driven, Prospective, Randomised, Double-blind, Multi-centre Trial Initiated by the European Society of Cardiology and AFNET
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Atrial fibrillation (AF) is a common cause of stroke, especially ischemic stroke. So far, all available data that demonstrate a beneficial effect of oral anticoagulation for stroke prevention have been collected in populations with AF documented by conventional ECG recordings. It is well established that a large proportion of AF episodes remain undiagnosed ("silent AF"), and many of these patients present with a stroke as the first clinical sign of AF. Earlier initiation of anticoagulation could prevent such events. Continuous monitoring of atrial rhythm by implanted devices could close this diagnostic gap. Pacemakers, defibrillators, and cardiac resynchronisation devices already provide automated algorithms alerting to the occurrence of highly organised atrial tachyarrhythmia episodes, also called "subclinical atrial fibrillation" or, more commonly, "atrial high rate episodes" (AHRE). Data from large prospectively followed patient cohorts demonstrated that stroke rate is increased in patients with AHRE. A sizeable portion of these patients develops clinically detected AF over time. In these patients, AHRE can be considered as an early manifestation of paroxysmal AF. A few AHRE patients do not develop clinically overt AF, and the absolute stroke rates are lower in patients with AHRE when compared to stroke rates in patients with clinically diagnosed AF. In light of the bleeding complications associated with oral anticoagulant therapy, there is thus uncertainty about the optimal antithrombotic therapy in patients with AHREs.
The Non-vitamin K antagonist Oral anticoagulants (NOACs) provide similar or slightly better stroke prevention, and appear slightly safer compared to vitamin K antagonists (VKAs). In addition, no individual therapy adjustment of NOACs has to be performed. Edoxaban, a newly introduced NOAC, at a dose regime of 60 mg once daily (OD) has a favourable profile compared to dose-adjusted VKA therapy: In the ENGAGE-TIMI 48 trial, edoxaban prevented strokes at least as effectively as VKA therapy but caused less major bleeding events than VKA therapy.
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
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Multiple Locations, Austria
- Several sites
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Multiple Locations, Belgium
- Several sites
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Multiple Locations, Bulgaria
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Multiple Locations, Czechia
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Multiple Locations, Denmark
- Several
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Multiple Locations, France
- Several
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Multiple Locations, Germany
- Several sites
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Multiple Locations, Greece
- Several
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Multiple Locations, Hungary
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Multiple Locations, Italy
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Multiple Locations, Netherlands
- Several
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Multiple Locations, Poland
- Several
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Multiple Locations, Portugal
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Multiple Locations, Romania
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Multiple Locations, Spain
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Multiple Locations, Sweden
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Multiple Locations, Ukraine
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Multiple Locations, United Kingdom
- Several
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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 (refer to Appendix XIII)
- AHRE (≥ 170 bpm atrial rate and ≥ 6 min duration) documented by the implanted device via its atrial lead and stored digitally. 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
- Provision of signed informed consent
- 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 antihyper-tensive 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
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)
- All persons exempt from participation in a clinical trial by law
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Active Comparator: ASA or Placebo
Either one tablet of ASA 100 mg plus one placebo tablet matching in colour, form and size to edoxaban 60 mg or one placebo tablet matching in colour, weight, form and size to ASA 100 mg plus one placebo tablet matching in colour, form and size to edoxaban 60 mg will be administered per day depending on the indication for use of antiplatelet therapy as assessed by the responsible investigator
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ASA 100 mg tablets or Placebo, based on accepted indication for the latter, including peripherial or coronary artery disease, a prior myocardial infarction, or a prior stroke.
Other Names:
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Experimental: Edoxaban
Edoxaban will be applied in NOAH at the therapeutic dose approved for stroke prevention in non-valvular AF, i.e. 60 mg OD with a reduction of dose to 30 mg OD in patients with one of the following characteristics: Impaired renal function (CrCl 15-50 ml/min), or low body weight (≤60 kg), or patients receiving the glycoprotein-P inhibitors cyclosporin, dronedarone, erythromycin, or ketoconazole. |
Edoxaban will be applied at the therapeutic dose approved for stroke prevention in non-valvular AF, i.e. 60 mg OD with a reduction of dose to 30 mg OD in patients with one of the following characteristics: Impaired renal function (CrCl 15-50 ml/min), or low body weight (≤60 kg), or patients receiving the glycoprotein-P inhibitors cyclosporin, dronedarone, erythromycin, or ketoconazole.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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stroke, systemic embolism, or cardiovascular death
Time Frame: 28 months
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Time from randomisation to the first occurrence of stroke, systemic embolism, or cardiovascular death
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28 months
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Components of the primary outcome
Time Frame: 28 months
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All-cause death Major bleeding events according to the ISTH definitions Quality of life changes at 12 and 24 months compared to baseline Patient satisfaction at 12 and 24 months compared to baseline Cost effectiveness and health resource utilisation Patient autonomy changes at 12 and 24 months compared to baseline including chronic consequences of stroke (aphasia, hemianopia ("mild stroke")) Cognitive function at 12 and 24 months compared to baseline
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28 months
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Major Adverse Cardiac Events (MACEs: cardiac death, myocardial infarction, acute coronary syndrome (ACS)
Time Frame: 28 months
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PCI, CABG
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28 months
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All-cause death
Time Frame: 28 months
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All-cause death
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28 months
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Major bleeding events
Time Frame: 28 months
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according to the International Society on Thrombosis and Haemostasis (ISTH) definitions
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28 months
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Quality of life changes at 12 and 24 months compared to baseline
Time Frame: 28 months
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assessed by EQ-5D including its visual-analogue scale and by the Karnofsky scale
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28 months
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Patient satisfaction at 12 and 24 months compared to baseline
Time Frame: 28 months
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assessed by PACT-Q
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28 months
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Cost effectiveness and health resource utilisation
Time Frame: 28 months
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estimated by quantification of relevant events, interventions, nights spent in hospital and cardiovascular therapies
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28 months
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Changes of autonomy status in patients with stroke during study participation
Time Frame: 28 Months
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potentially assessed at each FU visit by modified Rankin scale; a maximum of 2 subsequent assessments in FU per patient with stroke should be performed
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28 Months
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Cognitive function
Time Frame: 28 months
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MoCA test at 12 and 24 months compared to baseline
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28 months
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Paulus Kirchhof, Prof. Dr., University Clinic of Hamburg-Eppendorf, Hamburg, Germany
Publications and helpful links
General Publications
- Bertaglia E, Blank B, Blomstrom-Lundqvist C, Brandes A, Cabanelas N, Dan GA, Dichtl W, Goette A, de Groot JR, Lubinski A, Marijon E, Merkely B, Mont L, Piorkowski C, Sarkozy A, Sulke N, Vardas P, Velchev V, Wichterle D, Kirchhof P. Atrial high-rate episodes: prevalence, stroke risk, implications for management, and clinical gaps in evidence. Europace. 2019 Oct 1;21(10):1459-1467. doi: 10.1093/europace/euz172.
- Kirchhof P, Blank BF, Calvert M, Camm AJ, Chlouverakis G, Diener HC, Goette A, Huening A, Lip GYH, Simantirakis E, Vardas P. Probing oral anticoagulation in patients with atrial high rate episodes: Rationale and design of the Non-vitamin K antagonist Oral anticoagulants in patients with Atrial High rate episodes (NOAH-AFNET 6) trial. Am Heart J. 2017 Aug;190:12-18. doi: 10.1016/j.ahj.2017.04.015. Epub 2017 May 3.
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- NOAH - AFNET 6
- 2015-003997-33 (EudraCT Number)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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