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

NCT02618577 | Terminated Phase 3 Results DMC

• 2 other identifiers: NOAH - AFNET 62015-003997-33
• Study Type: interventional
• Target: 2,608
• Locations: 18 countries
• Sites: 18

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.

Conditions

Atrial High Rate Episodes

Keywords

Anticoagulation; Atrial High Rate Episodes; Atrial Fibrillation; VKA; NOAC

Outcome Measures

Primary Outcomes (1)

• 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.

  28 months

Secondary Outcomes (10)

• Components of the Primary Outcome, Stroke

  28 months

• Major Adverse Cardiac Events (MACEs: Cardiac Death, Myocardial Infarction, Acute Coronary Syndrome (ACS)

  28 months

• All-cause Death

  28 months

• Major Bleeding Events

  28 months

• Quality of Life Changes at 12 and 24 Months Compared to Baseline

  Baseline, 12 months and 24 months.

Study Arms (2)

Edoxaban

EXPERIMENTAL

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

ASA or Placebo

ACTIVE COMPARATOR

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

Interventions

Edoxaban DRUG

Edoxaban will be applied at the therapeutic dose approved for stroke prevention in non-valvular AF

Also known as: Lixiana, Savaysa

Edoxaban

ASA DRUG

ASA 100 mg tablets or Placebo, based on accepted indication for the latter, including peripheral or coronary artery disease, a prior myocardial infarction, or a prior stroke.

Also known as: ASS

ASA or Placebo

Eligibility Criteria

• Age: 65 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Atrial Fibrillation Network: lead
• Daiichi Sankyo Europe, GmbH, a Daiichi Sankyo Company: collaborator
• Deutsches Zentrum für Herz-Kreislauf-Forschung (DZHK): collaborator

Study Sites (18)

Several Sites

Multiple Locations, Austria

Location

Several Sites

Multiple Locations, Belgium

Location

Several

Multiple Locations, Bulgaria

Location

Several

Multiple Locations, Czechia

Location

Several

Multiple Locations, Denmark

Location

Several

Multiple Locations, France

Location

Several Sites

Multiple Locations, Germany

Location

Several

Multiple Locations, Greece

Location

Several

Multiple Locations, Hungary

Location

Several

Multiple Locations, Italy

Location

Several

Multiple Locations, Netherlands

Location

Several

Multiple Locations, Poland

Location

Several

Multiple Locations, Portugal

Location

Several

Multiple Locations, Romania

Location

Several

Multiple Locations, Spain

Location

Several

Multiple Locations, Sweden

Location

Several

Multiple Locations, Ukraine

Location

Several

Multiple Locations, United Kingdom

Location

Related Publications (3)

• 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.

  PMID: 31377792 BACKGROUND

• 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.

  PMID: 28760205 BACKGROUND

• Kirchhof P, Toennis T, Goette A, Camm AJ, Diener HC, Becher N, Bertaglia E, Blomstrom Lundqvist C, Borlich M, Brandes A, Cabanelas N, Calvert M, Chlouverakis G, Dan GA, de Groot JR, Dichtl W, Kravchuk B, Lubinski A, Marijon E, Merkely B, Mont L, Ozga AK, Rajappan K, Sarkozy A, Scherr D, Sznajder R, Velchev V, Wichterle D, Sehner S, Simantirakis E, Lip GYH, Vardas P, Schotten U, Zapf A; NOAH-AFNET 6 Investigators; NOAH-AFNET6 sites and investigators. Anticoagulation with Edoxaban in Patients with Atrial High-Rate Episodes. N Engl J Med. 2023 Sep 28;389(13):1167-1179. doi: 10.1056/NEJMoa2303062. Epub 2023 Aug 25.

  PMID: 37622677 DERIVED

Related Links

• NOAH Trial

MeSH Terms

Conditions

Atrial Fibrillation

Interventions

edoxaban

Condition Hierarchy (Ancestors)

Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

The trial does not have sufficient power to detect or rule out a small beneficial effect of oral anticoagulation on the prevention of stroke. The generalizability of these findings with edoxaban to other NOACs is not known.

Results Point of Contact

• Title: Prof. Dr. Paulus Kirchhof
• Organization: Universitätsklinikum Hamburg-Eppendorf

p.kirchhof@uke.de

+49 (0)40 7410-52438

Study Officials

• Paulus Kirchhof, Prof. Dr.

  University Clinic of Hamburg-Eppendorf, Hamburg, Germany

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Phase 3b

Study Record Dates

• First Submitted: November 27, 2015
• First Posted: December 1, 2015
• Study Start: February 1, 2016
• Primary Completion: December 31, 2022
• Study Completion: December 31, 2022
• Last Updated: February 6, 2025
• Results First Posted: February 6, 2025

Record last verified: 2025-02

Locations

CZ (1); IT (1); RO (1); ES (1); HU (1); PT (1); PL (1); DK (1); DE (1); FR (1); AU (1); BU (1); SE (1); UA (1); BE (1); GB (1); GR (1); NL (1)