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NCT02618577 Clinical Trial

Non-vitamin K Antagonist Oral Anticoagulants in Patients With Atrial High Rate Episodes

Atrial High Rate Episodes Clinical Trial

— NOAH  

Official title:
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

Clinical Trial Details — Status: Terminated

Administrative data
NCT number NCT02618577
Other study ID # NOAH - AFNET 6
Secondary ID 2015-003997-33
Status Terminated
Phase Phase 3
First received
Last updated
Start date February 2016
Est. completion date December 31, 2022

Study information
Verified date July 2023
Source Atrial Fibrillation Network
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility
Status Terminated
Enrollment 2608
Est. completion date December 31, 2022
Est. primary completion date December 31, 2022
Accepts healthy volunteers No
Gender All
Age group 65 Years and older
Eligibility 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 Design

Related Conditions & MeSH terms

Intervention

Drug:
• Edoxaban
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.
• ASA
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.

Locations
Country Name City State
Austria Several Sites Multiple Locations
Belgium Several Sites Multiple Locations
Bulgaria Several Multiple Locations
Czechia Several Multiple Locations
Denmark Several Multiple Locations
France Several Multiple Locations
Germany Several Sites Multiple Locations
Greece Several Multiple Locations
Hungary Several Multiple Locations
Italy Several Multiple Locations
Netherlands Several Multiple Locations
Poland Several Multiple Locations
Portugal Several Multiple Locations
Romania Several Multiple Locations
Spain Several Multiple Locations
Sweden Several Multiple Locations
Ukraine Several Multiple Locations
United Kingdom Several Multiple Locations

Sponsors (3)
Lead Sponsor Collaborator
Atrial Fibrillation Network Daiichi Sankyo Europe, GmbH, a Daiichi Sankyo Company, Deutsches Zentrum für Herz-Kreislauf-Forschung (DZHK)

Countries where clinical trial is conducted

Austria,  Belgium,  Bulgaria,  Czechia,  Denmark,  France,  Germany,  Greece,  Hungary,  Italy,  Netherlands,  Poland,  Portugal,  Romania,  Spain,  Sweden,  Ukraine,  United Kingdom, 

References & Publications (2)

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. — View Citation

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. — View Citation

Outcome
Type Measure Description Time frame Safety issue
Primary stroke, systemic embolism, or cardiovascular death Time from randomisation to the first occurrence of stroke, systemic embolism, or cardiovascular death 28 months
Secondary Components of the primary outcome 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 28 months
Secondary Major Adverse Cardiac Events (MACEs: cardiac death, myocardial infarction, acute coronary syndrome (ACS) PCI, CABG 28 months
Secondary All-cause death All-cause death 28 months
Secondary Major bleeding events according to the International Society on Thrombosis and Haemostasis (ISTH) definitions 28 months
Secondary Quality of life changes at 12 and 24 months compared to baseline assessed by EQ-5D including its visual-analogue scale and by the Karnofsky scale 28 months
Secondary Patient satisfaction at 12 and 24 months compared to baseline assessed by PACT-Q 28 months
Secondary Cost effectiveness and health resource utilisation estimated by quantification of relevant events, interventions, nights spent in hospital and cardiovascular therapies 28 months
Secondary Changes of autonomy status in patients with stroke during study participation 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 28 Months
Secondary Cognitive function MoCA test at 12 and 24 months compared to baseline 28 months

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