We updated the design of this site on December 18, 2017. Learn more.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02618577
Recruitment Status : Recruiting
First Posted : December 1, 2015
Last Update Posted : October 20, 2017
Sponsor:
Collaborators:
Information provided by (Responsible Party):

Study Description
Brief 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.

Condition or disease Intervention/treatment Phase
Atrial High Rate Episodes Drug: Edoxaban Drug: ASA Phase 3

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 Design

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 3400 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Prevention
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
Study Start Date : February 2016
Estimated Primary Completion Date : May 2019
Estimated Study Completion Date : September 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Blood Thinners
Drug Information available for: Edoxaban
U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
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.

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.

Other Names:
  • Lixiana
  • Savaysa
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
Drug: ASA
ASA 100 mg tablets or Placebo
Other Name: ASS


Outcome Measures

Primary Outcome Measures :
  1. Time from randomisation to the first occurrence of stroke, systemic embolism, or cardiovascular death [ Time Frame: 28 months ]

Secondary Outcome Measures :
  1. Components of the primary outcome [ Time Frame: 28 months ]
    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

  2. All-cause death, [ Time Frame: 28 months ]
  3. Major bleeding events according to the International Society on Thrombosis and Haemostasis (ISTH) definitions [ Time Frame: 28 months ]
  4. 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) [ Time Frame: 28 months ]
  5. Patient satisfaction at 12 and 24 months compared to baseline (assessed by modified EHRA score (36) and PACT-Q ) [ Time Frame: 28 months ]
  6. Cost effectiveness and health resource utilisation estimated by quantification of relevant events, interventions, nights spent in hospital and cardiovascular therapies, [ Time Frame: 28 months ]
  7. Patient autonomy changes at 12 and 24 months compared to baseline including chronic consequences of stroke (aphasia, hemianopia ("mild stroke")) as assessed by modified Rankin score and NIHSS in conjunction with Karnofsky and EQ-5D [ Time Frame: 28 Months ]
  8. Cognitive function (MoCA) at 12 and 24 months compared to baseline [ Time Frame: 28 months ]

Eligibility Criteria

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   65 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria
  1. Implanted pacemaker or defibrillator with feature of detection of AHRE, implanted at least 2 months prior to randomisation.
  2. AHRE detection feature activated adequately according to "Suggestions for optimal programming of devices for adequate detection of AHRE" (refer to Appendix VIII).
  3. AHRE (≥ 180 bpm atrial rate and ≥ 6 min duration) documented by the implanted device via its atrial lead and stored digitally. AHRE episodes detected in the first 2 months after implantation of a new device involving placement or repositioning of electrodes are not counted. 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 electrodes, are eligible.
  4. Age ≥ 65 years.
  5. In addition, at least one of the following cardiovascular conditions leading to a 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 (peripheral, carotid/cerebral, or aortic plaques on transesophageal echocardio-gram [TEE]).

  6. Provision of signed informed consent.

Exclusion Criteria:

General exclusion criteria E1. Any disease that limits life expectancy to less than 1 year. E2. Participation in another controlled clinical trial, either within the past two months or still ongoing.

E3. Previous participation in the present trial NOAH. E4. Drug abuse or clinically manifest alcohol abuse. Exclusion criteria related to a cardiac condition E5. Any history of overt AF or atrial flutter. E6. Indication for oral anticoagulation (e.g. deep venous thrombosis). E7. Contraindication for oral anticoagulation in general. E8. Contraindication for edoxaban as stated in the current SmPC. E9. Indication for long-term antiplatelet therapy other than acetylsalicylic acid, especially dual antiplatelet therapy (DAPT) with acetylsalicylic acid and one of the following agents: clopidogrel, prasugrel, or ticagrelor. 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.

E10. Acute coronary syndrome, coronary revascularisation (PCI or bypass surgery), or overt stroke within 30 days prior to randomisation.

Exclusion criteria based on laboratory abnormalities E11. End stage renal disease (creatinine clearance (CrCl) < 15 ml/min as calculated by the Cockcroft-Gault method).

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02618577


Contacts
Contact: Paulus Kirchhof, Prof. Dr. +44 121 414 ext 7042 p.kirchhof@bham.ac.uk
Contact: Benjamin Blank, Dr. 0049 251 980 ext 1340 benjamin.blank@af-net.eu

Locations
Belgium
Several Sites Not yet recruiting
Different, Belgium
Denmark
Several Sites Not yet recruiting
Different, Denmark
Germany
Several Sites Recruiting
Different, Germany
Sponsors and Collaborators
Atrial Fibrillation Network
Daiichi Sankyo Europe, GmbH
Deutsches Zentrum für Herz-Kreislauf-Forschung (DZHK)
Investigators
Principal Investigator: Paulus Kirchhof, Prof. Dr. University of Birmingham Centre for Cardiovascular Scienes
More Information

Additional Information:
Responsible Party: Atrial Fibrillation Network
ClinicalTrials.gov Identifier: NCT02618577     History of Changes
Other Study ID Numbers: NOAH - AFNET 6
2015-003997-33 ( EudraCT Number )
First Posted: December 1, 2015    Key Record Dates
Last Update Posted: October 20, 2017
Last Verified: October 2017

Keywords provided by Atrial Fibrillation Network:
Anticoagulation
atrial high rate episodes
Atrial Fibrillation
VKA
NOAC

Additional relevant MeSH terms:
Edoxaban
Anticoagulants
Factor Xa Inhibitors
Antithrombins
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action