NCT01288352

Brief Summary

EAST prospectively tests the hypothesis that an early, structured rhythm control therapy based on antiarrhythmic drugs and catheter ablation can prevent atrial fibrillation (AF) related complications in patients with AF when compared to usual care. Patients will be randomized to early therapy or usual care. In the early therapy group, patients will receive either catheter ablation (usually by pulmonary vein isolation), or adequate antiarrhythmic drug therapy at an early time point. The initial therapy will be selected by the local investigator. Upon AF recurrence, both modalities will be combined. Usual care will be conducted following the 2010European Society of Cardiology ( ESC )guidelines for AF treatment. Early rhythm control therapy will be guided by Electrocardiogram (ECG) monitoring.

Trial Health

98
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
2,789

participants targeted

Target at P75+ for phase_4 atrial-fibrillation

Timeline
Completed

Started Jul 2011

Longer than P75 for phase_4 atrial-fibrillation

Geographic Reach
11 countries

11 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

February 1, 2011

Completed
1 day until next milestone

First Posted

Study publicly available on registry

February 2, 2011

Completed
5 months until next milestone

Study Start

First participant enrolled

July 1, 2011

Completed
8.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 6, 2020

Completed
3 months until next milestone

Study Completion

Last participant's last visit for all outcomes

May 31, 2020

Completed
Last Updated

July 23, 2020

Status Verified

June 1, 2020

Enrollment Period

8.7 years

First QC Date

February 1, 2011

Last Update Submit

July 21, 2020

Conditions

Atrial FibrillationStroke

Keywords

early treatmentrhythm controlatrial fibrillationcardiovascular complications

Outcome Measures

Primary Outcomes (1)

  • A composite of cardiovascular death, stroke and hospitalization due to worsening of heart failure or due to acute coronary syndrome.

    The 1st co-primary outcome parameter is defined as the time to the first occurrence of a composite of cardiovascular death, stroke / transient ischemic attack (TIA), and hospitalization due to worsening of heart failure or due to acute coronary syndrome. The second co-primary outcome is nights spent in hospital per year. The 2nd co-primary outcome is nights spent in hospital per year.

    8 years

Secondary Outcomes (1)

  • Key 2d outcomes: Each of the components of the 1st outcome, time to recurrent AF, cv hospitalizations, all-cause hospitalizations, left ventricular function, QL, cognitive function, cost of therapy.

    8 years

Study Arms (2)

Usual care

NO INTERVENTION

Usual care closely follows the suggestions laid out in the current European Society of Cardiology (ESC) guidelines for AF treatment. In addition to antithrombotic therapy and therapy of underlying heart disease, usual care usually consists of an initial attempt to control symptoms by rate control therapy. Rhythm control interventions are recommended when symptoms can not be controlled by optimal rate control therapy in the usual care group.

early standardised rhythm control

OTHER

Patients in the early therapy group will be treated following the same therapeutic recommendations of the ESC guidelines as the usual care group. In addition, rhythm control therapy will be initiated early with the aim of preventing recurrence and delaying or preventing progression of AF. Early-onset rhythm control therapy can consist of: 1. Optimal antiarrhythmic drug therapy (Dronedarone, Amiodarone, Flecainide, Propafenone), 2. Catheter ablation with the aim of pulmonary vein isolation (PVI), 3. Antiarrhythmic drug therapy and catheter ablation may be supplemented by early cardioversion in patients with persistent AF. All individual treatment decisions will be taken by the treating study physician considering the labelling of the procedures and drugs and patient preferences.

Other: early standardised rhythm control

Interventions

early standardised rhythm controlOTHER

Patients in the early therapy group will be treated following the same therapeutic recommendations of the ESC guidelines as the usual care group. In addition, rhythm control therapy will be initiated early with the aim of preventing recurrence and delaying or preventing progression of AF. Early-onset rhythm control therapy can consist of: 1. Optimal antiarrhythmic drug therapy 2. Catheter ablation with the aim of pulmonary vein isolation (PVI), 3. Antiarrhythmic drug therapy and catheter ablation may be combined and supplemented by early cardioversion in patients with persistent AF. All individual treatment decisions will be taken by the treating study physician considering the labelling of the procedures and drugs and patient preferences.

early standardised rhythm control

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Recent-onset AF (≤ 1 year prior to enrolment)
  • At least one ECG within recent 12 months that documents AF whereas the AF episode must last longer than 30 sec.
  • One of the following:
  • age \> 75 years or
  • prior stroke or transient ischemic attack
  • OR two of the following:
  • age \> 65 years,
  • female sex,
  • arterial hypertension (chronic treatment for hypertension, estimated need for continuous antihypertensive therapy or resting blood pressure \> 145/90 mmHg),
  • diabetes mellitus (treated by drugs or insulin) or impaired glucose tolerance
  • severe coronary artery disease (previous myocardial infarction, CABG or PCI)
  • stable heart failure (NYHA II or LVEF \<50%),
  • left ventricular hypertrophy on echocardiography (more than 15 mm wall thickness),
  • chronic kidney disease (MDRD stage III or IV),
  • peripheral artery disease.
  • +2 more criteria

You may not qualify if:

  • Any disease that limits life expectancy to less than 1 year.
  • Participation in another clinical trial, either within the past two months or ongoing
  • Previous participation in the EAST trial.
  • Pregnant women or women of childbearing potential not on adequate birth control: only women with a highly effective method of contraception \[oral contraception or intra-uterine device (IUD)\] or sterile women can be randomized.
  • Breastfeeding women.
  • Drug abuse.
  • Prior AF ablation or surgical therapy of AF.
  • Previous therapy failure on amiodarone, e.g. patients who suffered from symptomatic recurrent AF that required escalation of therapy while on amiodarone.
  • Patients not suitable for rhythm control of AF.
  • Severe mitral valve stenosis.
  • Prosthetic mitral valve.
  • Clinically relevant hepatic dysfunction requiring specific therapy.
  • Clinically manifest thyroid dysfunction requiring therapy. After successful treatment of thyroid dysfunction, patients may be enrolled when their thyroid function is controlled.
  • Severe renal dysfunction (stage V, requiring or almost requiring dialysis).

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (11)

14 Sites

Different, Belgium

Location

4 Sites

Different, Czechia

Location

2 Sites

Different, Denmark

Location

2 Sites

Different, France

Location

51 Sites

Different, Germany

Location

12 Sites

Different, Italy

Location

13 Sites

Different, Netherlands

Location

5 Sites

Different, Poland

Location

10 Sites

Different, Spain

Location

5 Sites

Different, Switzerland

Location

22 Sites

Different, United Kingdom

Location

Related Publications (15)

  • International Landmark EAST Study Inverstigates Treatment Options for Atrial Fibrillation

    RESULT

  • Metzner A, Willems S, Borof K, Breithardt G, Camm AJ, Crijns HJGM, Eckardt L, Fabritz L, Gessler N, Goette A, Reissmann B, Schnabel RB, Schotten U, Zapf A, Rillig A, Kirchhof P. Diabetes and Obesity and Treatment Effect of Early Rhythm Control vs Usual Care in Patients With Atrial Fibrillation: A Secondary Analysis of the EAST-AFNET 4 Randomized Clinical Trial. JAMA Cardiol. 2025 Sep 1;10(9):932-941. doi: 10.1001/jamacardio.2025.2374.

    PMID: 40737012DERIVED

  • Rottner L, Lemoine MD, Eckardt L, Borof K, Camm AJ, Goette A, Breithardt G, Metzner A, Schotten U, Zapf A, Heidbuchel H, Willems S, Crijns H, Schnabel RB, Fabritz L, Magnussen C, Rillig A, Kirchhof P. Safety and efficacy of amiodarone and dronedarone for early rhythm control in EAST-AFNET 4. Clin Res Cardiol. 2025 May 19. doi: 10.1007/s00392-025-02637-0. Online ahead of print.

    PMID: 40387892DERIVED

  • Kirchhof P, Camm AJ, Crijns HJGM, Piccini JP, Torp-Pedersen C, McKindley DS, Wieloch M, Hohnloser SH. Dronedarone provides effective early rhythm control: post-hoc analysis of the ATHENA trial using EAST-AFNET 4 criteria. Europace. 2025 Mar 28;27(4):euaf080. doi: 10.1093/europace/euaf080.

    PMID: 40295782DERIVED

  • Rillig A, Eckardt L, Borof K, Camm AJ, Crijns HJGM, Goette A, Breithardt G, Lemoine MD, Metzner A, Rottner L, Schotten U, Vettorazzi E, Wegscheider K, Zapf A, Heidbuchel H, Willems S, Fabritz L, Schnabel RB, Magnussen C, Kirchhof P. Safety and efficacy of long-term sodium channel blocker therapy for early rhythm control: the EAST-AFNET 4 trial. Europace. 2024 Jun 3;26(6):euae121. doi: 10.1093/europace/euae121.

    PMID: 38702961DERIVED

  • Kany S, Al-Taie C, Roselli C, Pirruccello JP, Borof K, Reinbold C, Suling A, Krause L, Reissmann B, Schnabel RB, Zeller T, Zapf A, Wegscheider K, Fabritz L, Ellinor PT, Kirchhof P. Association of genetic risk and outcomes in patients with atrial fibrillation: interactions with early rhythm control in the EAST-AFNET4 trial. Cardiovasc Res. 2023 Aug 7;119(9):1799-1810. doi: 10.1093/cvr/cvad027.

    PMID: 37264683DERIVED

  • Van Gelder IC, Ekrami NK, Borof K, Fetsch T, Magnussen C, Mulder BA, Schnabel R, Wegscheider K, Rienstra M, Kirchhof P; EAST-AFNET 4 Trial Investigators. Sex Differences in Early Rhythm Control of Atrial Fibrillation in the EAST-AFNET 4 Trial. J Am Coll Cardiol. 2023 Feb 28;81(8):845-847. doi: 10.1016/j.jacc.2022.12.011. No abstract available.

    PMID: 36813380DERIVED

  • Jensen M, Suling A, Metzner A, Schnabel RB, Borof K, Goette A, Haeusler KG, Zapf A, Wegscheider K, Fabritz L, Diener HC, Thomalla G, Kirchhof P. Early rhythm-control therapy for atrial fibrillation in patients with a history of stroke: a subgroup analysis of the EAST-AFNET 4 trial. Lancet Neurol. 2023 Jan;22(1):45-54. doi: 10.1016/S1474-4422(22)00436-7.

    PMID: 36517170DERIVED

  • Eckardt L, Sehner S, Suling A, Borof K, Breithardt G, Crijns H, Goette A, Wegscheider K, Zapf A, Camm J, Metzner A, Kirchhof P. Attaining sinus rhythm mediates improved outcome with early rhythm control therapy of atrial fibrillation: the EAST-AFNET 4 trial. Eur Heart J. 2022 Oct 21;43(40):4127-4144. doi: 10.1093/eurheartj/ehac471.

    PMID: 36036648DERIVED

  • Rillig A, Borof K, Breithardt G, Camm AJ, Crijns HJGM, Goette A, Kuck KH, Metzner A, Vardas P, Vettorazzi E, Wegscheider K, Zapf A, Kirchhof P. Early Rhythm Control in Patients With Atrial Fibrillation and High Comorbidity Burden. Circulation. 2022 Sep 13;146(11):836-847. doi: 10.1161/CIRCULATIONAHA.122.060274. Epub 2022 Aug 15.

    PMID: 35968706DERIVED

  • Goette A, Borof K, Breithardt G, Camm AJ, Crijns HJGM, Kuck KH, Wegscheider K, Kirchhof P; EAST-AFNET 4 Investigators. Presenting Pattern of Atrial Fibrillation and Outcomes of Early Rhythm Control Therapy. J Am Coll Cardiol. 2022 Jul 26;80(4):283-295. doi: 10.1016/j.jacc.2022.04.058.

    PMID: 35863844DERIVED

  • Willems S, Borof K, Brandes A, Breithardt G, Camm AJ, Crijns HJGM, Eckardt L, Gessler N, Goette A, Haegeli LM, Heidbuchel H, Kautzner J, Ng GA, Schnabel RB, Suling A, Szumowski L, Themistoclakis S, Vardas P, van Gelder IC, Wegscheider K, Kirchhof P. Systematic, early rhythm control strategy for atrial fibrillation in patients with or without symptoms: the EAST-AFNET 4 trial. Eur Heart J. 2022 Mar 21;43(12):1219-1230. doi: 10.1093/eurheartj/ehab593.

    PMID: 34447995DERIVED

  • Rillig A, Magnussen C, Ozga AK, Suling A, Brandes A, Breithardt G, Camm AJ, Crijns HJGM, Eckardt L, Elvan A, Goette A, Gulizia M, Haegeli L, Heidbuchel H, Kuck KH, Ng A, Szumowski L, van Gelder I, Wegscheider K, Kirchhof P. Early Rhythm Control Therapy in Patients With Atrial Fibrillation and Heart Failure. Circulation. 2021 Sep 14;144(11):845-858. doi: 10.1161/CIRCULATIONAHA.121.056323. Epub 2021 Jul 30.

    PMID: 34328366DERIVED

  • Kirchhof P, Camm AJ, Goette A, Brandes A, Eckardt L, Elvan A, Fetsch T, van Gelder IC, Haase D, Haegeli LM, Hamann F, Heidbuchel H, Hindricks G, Kautzner J, Kuck KH, Mont L, Ng GA, Rekosz J, Schoen N, Schotten U, Suling A, Taggeselle J, Themistoclakis S, Vettorazzi E, Vardas P, Wegscheider K, Willems S, Crijns HJGM, Breithardt G; EAST-AFNET 4 Trial Investigators. Early Rhythm-Control Therapy in Patients with Atrial Fibrillation. N Engl J Med. 2020 Oct 1;383(14):1305-1316. doi: 10.1056/NEJMoa2019422. Epub 2020 Aug 29.

    PMID: 32865375DERIVED

  • Kirchhof P, Breithardt G, Camm AJ, Crijns HJ, Kuck KH, Vardas P, Wegscheider K. Improving outcomes in patients with atrial fibrillation: rationale and design of the Early treatment of Atrial fibrillation for Stroke prevention Trial. Am Heart J. 2013 Sep;166(3):442-8. doi: 10.1016/j.ahj.2013.05.015. Epub 2013 Jul 30.

    PMID: 24016492DERIVED

MeSH Terms

Conditions

Atrial FibrillationStroke

Condition Hierarchy (Ancestors)

Arrhythmias, CardiacHeart DiseasesCardiovascular DiseasesPathologic ProcessesPathological Conditions, Signs and SymptomsCerebrovascular DisordersBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesVascular Diseases

Study Officials

  • Paulus Kirchhof, MD

    University of Birmingham Centre for Cardiovascular Sciences, Department of Cardiology, University Heart and Vascular Center UKE Hamburg, Hamburg, Germany

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
NONE
Purpose
PREVENTION
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

February 1, 2011

First Posted

February 2, 2011

Study Start

July 1, 2011

Primary Completion

March 6, 2020

Study Completion

May 31, 2020

Last Updated

July 23, 2020

Record last verified: 2020-06

Data Sharing

IPD Sharing
Will share

We will share all data that support published results of the trial. Additional data that have not been published will be withheld until six months after publication of these results. Data will be made available as required for specific, approved analyses. Data will be provided from locked, cleaned and de-identified study database. Requests will be reviewed by AFNET as per the predefined subanalysis plan.

Shared Documents
STUDY PROTOCOL, SAP, ICF
Time Frame
We will make data available starting six months after the publication of the primary results for 5 years.
Access Criteria
The Clinical Study Report (CSR) and the Analytic Code will be shared upon request to AFNET. This plan and the contact details will be made available on the EAST web site (www.easttrial.org) with additional information on planned and ongoing subanalyses conducted within the EAST trial team.

Locations

NL(1)IT(1)BE(1)ES(1)DE(1)FR(1)PL(1)GB(1)CZ(1)CH(1)DK(1)