NOAH is an investigator-initiated, prospective, parallel-group, double-blind, randomised, multi-centre trial. The objective of the trial is to demonstrate that oral anticoagulation using the NOAC edoxaban is superior to current therapy to pre-vent stroke, systemic embolism, or cardiovascular death in patients with AHRE and at least two stroke risk factors but without AF. The trial will be conducted in several European countries.
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
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
DOUBLE
Enrollment
2,608
Several Sites
Multiple Locations, Austria
Several Sites
Multiple Locations, Belgium
Several
Multiple Locations, Bulgaria
Composite of Stroke, Systemic Embolism, or Cardiovascular Death
Time from randomisation to the first occurrence of stroke, systemic embolism, or cardiovascular death; incidence of first occurence of outcome measure.
Time frame: 28 months
Components of the Primary Outcome, Stroke
Time from randomisation to the first occurrence of ischemic stroke; incidence of first occurence of outcome measure.
Time frame: 28 months
Major Adverse Cardiac Events (MACEs: Cardiac Death, Myocardial Infarction, Acute Coronary Syndrome (ACS)
PCI, CABG
Time frame: 28 months
All-cause Death
All-cause death
Time frame: 28 months
Major Bleeding Events
according to the International Society on Thrombosis and Haemostasis (ISTH) definitions
Time frame: 28 months
Quality of Life Changes at 12 and 24 Months Compared to Baseline
Adjusted mean change from baseline at 12 and 24 months of Quality of life as assessed by the EuroQol Group 5-Dimension 5-Level questionnaire (EQ-5D-5L): The resulting score of the UK index ranges from 1 (for the best state) to - 0.285 (for the worst state), with 5.1% of the states valued as worse than dead. EQ5D- VAS: visual-analogue scale (0 worst to 100 best). Subscales of the UK index score were combined by adding up EQ-5D-5L index values with STATA using the English (ENG) Devlin value set, Version 1.1 (Updated 01/12/2020). Karnofsky Performance Scale is an 11-point scale from 0 to 100 (0 worst to 100 best).
Time frame: Baseline, 12 months and 24 months.
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Several
Multiple Locations, Czechia
Several
Multiple Locations, Denmark
Several
Multiple Locations, France
Several Sites
Multiple Locations, Germany
Several
Multiple Locations, Greece
Several
Multiple Locations, Hungary
Several
Multiple Locations, Italy
...and 8 more locations
Patient Satisfaction at 12 and 24 Months Compared to Baseline
Adjusted change from baseline at 12 and 24 months measured by the Perception of Anticoagulant Treatment Questionnaire: For convenience score, a 0 - 100 scale; for satisfaction score a 0 - 100 scale; for both scores, the higher the score, the higher the convenience/satisfaction.
Time frame: Baseline, 12 months and 24 months.
Cost Effectiveness and Health Resource Utilisation
estimated by quantification of relevant events, interventions, nights spent in hospital and cardiovascular therapies
Time frame: 28 months
Autonomy Status
Autonomy status only in patients with stroke during study participation, assessed at 24 month by modified Rankin scale. (Score ranges from 1 to 8, a higher score indicates a higher grade of disability)
Time frame: Baseline and 24 months
Components of the Primary Outcome, Systemic Embolism
Time from randomisation to the first occurrence of systemic embolism; incidence of first occurence of outcome measure.
Time frame: 28 months
Components of the Primary Outcome, Cardiovascular Death
Time from randomisation to the first occurrence of cardiovascular death; incidence of first occurence of outcome measure.
Time frame: 28 months