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…
ID
Source
Brief title
Condition
- Cardiac disorders, signs and symptoms NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
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.
Secondary outcome
-Components of the primary outcome
-Major Adverse Cardiac Events (MACEs: cardiovascular death, myocardial
infarction, acute coronary syndrome (ACS), PCI, CABG)
- stroke or systemic arterial embolism
-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
Background summary
Atrial fibrillation (AF) is a common cause of stroke, especially ischemic
stroke. So far, all available data that demonstrate a beneficial effect of oral
anti-coagulation 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.
Pace-makers, 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 AHRE.
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 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.
.
Study design
Investigator-initiated, prospective, parallel-group, randomised, double-blind,
multi-centre trial. Although it can be argued that the indication tested is
within the registered label of edoxaban, NOAH * AFNET 6 will be conducted as a
phase IIIb study.
Intervention
not applicable
Study burden and risks
There are no additional risks in this study other than those which may occur
with therapy in clinical routine treatment for prevention of stroke. Even
simple procedures, e.g. blood sampling, may involve undesirable side effects.
These may include bruising at the puncture site or infections. However, the
overall risks in the study do not exceed the risks of adverse events in routine
clinical care.
Treatment with edoxaban or ASA may increase the risk of visible or occult
bleeding. However, the intensity and extent of bleeding may vary.
Mendelstr. 11
Münster 48149
DE
Mendelstr. 11
Münster 48149
DE
Listed location countries
Age
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 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.
-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
Exclusion criteria
- Patients with history of overt AF or atrial flutter
- patients with a clear contraindication for oral anticoagulation,
- patients with a clear need for oral anticoagulation,
- patients with indication for long-term antiplatelet therapy other than
acetylsalicylic acid (ASA) or a need for treatment with any antiplatelet agent
in addition to edoxaban, especially dual antiplatelet therapy (DAPT), are not
suitable for NOAH - AFNET 6.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2015-003997-33-NL |
| ISRCTN | ISRCTN17309850 |
| CCMO | NL58839.018.16 |