Condition category
Circulatory System
Date applied
07/12/2010
Date assigned
10/01/2011
Last edited
16/03/2016
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
Atrial fibrillation is a heart condition that results in an irregular, often abnormally fast heart rate, which also increases the risk of having a stroke. It can be treated with anti-arrhythmic drugs that restore a normal heart rhythm and rate. It can also be treated with catheter ablation, a procedure where the diseased area of the heart is very carefully destroyed to interrupt the fast, irregular electrical impulses. The aim of this study is to find out whether early, structured rhythm control treatment using anti-arrhythmic drugs and catheter ablation can prevent complications (e.g., stroke) in patients with atrial fibrillation.

Who can participate?
Patients aged 18 and over who have had atrial fibrillation for a year or less and are at high risk of stroke

What does the study involve?
Patients are randomly allocated to receive early treatment or usual care. In the early treatment group, patients receive either catheter ablation or anti-arrhythmic drug treatment at an early timepoint. The initial treatment is selected by the doctor. If atrial fibrillation returns both treatments are combined. Usual care follows the current guidelines for atrial fibrillation treatment. All patients are followed up every 6 months by questionnaire and by outpatient follow-up visits at 12, 24 and 36 months.

What are the possible benefits and risks of participating?
Not provided at time of registration

Where is the study run from?
CRI - The Clinical Research Institute GmbH (Germany)

When is the study starting and how long is it expected to run for?
July 2011 to December 2019

Who is funding the study?
German Atrial Fibrillation Network (Germany)

Who is the main contact?
Prof Paulus Kirchhof

Trial website

http://www.easttrial.org

Contact information

Type

Scientific

Primary contact

Prof Paulus Kirchhof

ORCID ID

Contact details

c/o Elisabeth Freund
Projektmanagement
CRI - The Clinical Research Institute GmbH
Arnulfstraße 19
München
80335
Germany

Additional identifiers

EudraCT number

2010-021258-20

ClinicalTrials.gov number

NCT01288352

Protocol/serial number

2010-021258-20

Study information

Scientific title

An investigator-driven, prospective, parallel-group, randomised, open, blinded outcome assessment (PROBE-design), multicentre trial for the prevention of stroke in high-risk subjects with atrial fibrillation

Acronym

EAST

Study hypothesis

EAST prospectively tests the hypothesis that an early, structured rhythm control therapy based on anti-arrhythmic drugs and catheter ablation can prevent atrial fibrillation (AF) related complications in patients with AF when compared to usual care.

Patients will be randomised to early therapy or usual care. In the early therapy group, patients will receive either catheter ablation (usually by pulmonary vein isolation), or adequate anti-arrhythmic drug therapy at an early timepoint. 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 current ESC guidelines for AF treatment. Early rhythm control therapy will be guided by ECG monitoring.

Ethics approval

Ethikkommission der Ärztekammer Westfalen-Lippe und der Medizinischen Fakultät der Westfälischen Wilhelms-Universität Münster, 09/02/2011, ref: 2010-274-f-A

Study design

Phase IV randomised open prospective two-armed parallel-group multicentre trial

Primary study design

Interventional

Secondary study design

Randomised parallel trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Recent onset atrial fibrillation/stroke risk

Intervention

Usual care group:
Usual care closely follows the suggestions laid out in the current ESC guidelines for AF. In addition to anti-thrombotic therapy and therapy of underlying heart disease, usual care usually consists of an initial attempt to control symptoms by rate control therapy (Metoprolol, Bisoprolol, Digoxin, Digitoxin, Verapamil). Rhythm control interventions are only indicated when symptoms cannot be controlled by optimal rate control therapy in the usual care group.

Early therapy group:
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. Anti-arrhythmic 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.

Duration:
EAST is an event-driven trial, i.e. the trial will be terminated after 685 evaluable primary outcomes have occured. A duration of the entire trial of around 8 years is expected. All patients will be followed-up until the end of the trial with a minimum follow-up period of two and a half years.

Intervention type

Drug

Phase

Phase IV

Drug names

Primary outcome measures

1. A composite of cardiovascular death, stroke/transient ischaemic attack (TIA), and hospitalisation due to worsening of heart failure or due to acute coronary syndrome
2. Nights spent in hospital per year

Secondary outcome measures

1. Cardiovascular death
2. Stroke/transient ischaemic attack
3. Worsening of heart failure assessed by hospitalisations
4. Acute coronary syndrome assessed by hospitalisations
5. Time to recurrent atrial fibrillation
6. Cardiovascular hospitalisations
7. All-cause hospitalisations
8. Left ventricular function assessed by transthoracic echocardiography at month 24 (+/- 2 months) after randomisation
9. Quality of life changes assessed by EQ-5D and 12-item short form health survey (SF-12) at month 24 (+/- 2 months) after randomisation
10. Cognitive function assessed by MoCA at month 24 (+/- 2 months) after randomisation

Overall trial start date

01/07/2011

Overall trial end date

01/12/2019

Reason abandoned

Eligibility

Participant inclusion criteria

1. Recent-onset AF (less than or equal to 1 year prior to enrolment)
2. At least one ECG within recent 12 months that documents AF whereas the AF episode must last longer than 30 seconds
3. One of the following:
3.1. Aged greater than 75 years, or
3.2. Prior stroke or transient ischaemic attack
OR two of the following:
3.3. Aged greater than 65 years
3.3. Female sex
3.4. Arterial hypertension (chronic treatment for hypertension, estimated need for continuous antihypertensive therapy or resting blood pressure greater than 145/90 mmHg)
3.5. Diabetes mellitus
3.6. Severe coronary artery disease (previous myocardial infarction, coronary artery bypass graft [CABG] or percutaneous coronary intervention [PCI])
3.7. Stable heart failure (New York Heart Association [NYHA] II or left ventricular ejection fraction [LVEF] less than 50%)
3.8. Left ventricular hypertrophy on echocardiography (more than 15 mm wall thickness)
3.9. Chronic kidney disease (Modified Diet in Renal Disease [MDRD] stage III or IV)
3.10. Peripheral artery disease
4. Provision of signed informed consent
5. Age greater than or equal to 18 years

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

2745 (first patient in on 28/07/2011)

Participant exclusion criteria

1. Any disease that limits life expectancy to less than 1 year
2. Participation in another clinical trial, either within the past two months or ongoing
3. Previous participation in the EAST trial
4. 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 randomised
5. Breastfeeding women
6. Drug abuse
7. Prior AF ablation or surgical therapy of AF
8. Previous therapy failure on amiodarone, e.g. patients who suffered from symptomatic recurrent AF that required escalation of therapy while on amiodarone
9. Patients not suitable for rhythm control of AF
10. Severe mitral valve stenosis
11. Prosthetic mitral valve
12. Clinically relevant hepatic dysfunction requiring specific therapy
13. Clinically manifest thyroid dysfunction requiring therapy. After successful treatment of thyroid dysfunction, patients may be enrolled when their thyroid function is controlled.
14. Severe renal dysfunction (stage V, requiring or almost requiring dialysis)

Recruitment start date

01/07/2011

Recruitment end date

31/12/2016

Locations

Countries of recruitment

Belgium, Czech Republic, Denmark, France, Germany, Italy, Netherlands, Poland, Spain, Switzerland, United Kingdom

Trial participating centre

CRI - The Clinical Research Institute GmbH
München
80335
Germany

Sponsor information

Organisation

German Atrial Fibrillation Network (Germany)

Sponsor details

Mendelstr. 11
Münster
48149
Germany

Sponsor type

Research organisation

Website

http://www.kompetenznetz-vorhofflimmern.de

Funders

Funder type

Research organisation

Funder name

German Atrial Fibrillation Network (Germany)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

2011 protocol in: http://www.ncbi.nlm.nih.gov/pubmed/21784740
2013 rationale and design in: http://www.ncbi.nlm.nih.gov/pubmed/24016492
2015 article in: http://www.ncbi.nlm.nih.gov/pubmed/25646394

Publication citations

  1. Protocol

    Van Gelder IC, Haegeli LM, Brandes A, Heidbuchel H, Aliot E, Kautzner J, Szumowski L, Mont L, Morgan J, Willems S, Themistoclakis S, Gulizia M, Elvan A, Smit MD, Kirchhof P, Rationale and current perspective for early rhythm control therapy in atrial fibrillation., Europace, 2011, 13, 11, 1517-1525, doi: 10.1093/europace/eur192.

  2. 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, 166, 3, 442-448, doi: 10.1016/j.ahj.2013.05.015.

  3. Aliot E, Brandes A, Eckardt L, Elvan A, Gulizia M, Heidbuchel H, Kautzner J, Mont L, Morgan J, Ng A, Szumowski L, Themistoclakis S, Van Gelder IC, Willems S, Kirchhof P, The EAST study: redefining the role of rhythmcontrol therapy in atrial fibrillation: EAST, the Early treatment of Atrial fibrillation for Stroke prevention Trial, Eur Heart J, 2015, 36, 5, 255-256, doi: 10.1093/eurheartj/ehu476.

Additional files

Editorial Notes

16/03/2016: Plain English summary added. On 10/07/2015 the following changes were made to the trial record: 1. The overall trial start date was changed from 01/04/2011 to 01/07/2011. 2. The overall trial end date was changed from 01/03/2017 to 01/12/2019. 3. The target number of participants was changed from 2810 to 2745.