Back to resultsEarly Treatment of Atrial Fibrillation for Stroke Prevention Trial (EAST)
Primary Purpose
Atrial Fibrillation, Stroke
Status
Completed
Phase
Phase 4
Locations
International
Study Type
Interventional
Intervention
early standardised rhythm control
Sponsored by
About this trial
This is an interventional prevention trial for Atrial Fibrillation focused on measuring early treatment, rhythm control, atrial fibrillation, cardiovascular complications
Eligibility Criteria
Inclusion Criteria:
- 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.
- Provision of signed informed consent.
- Age ≥ 18 years.
Exclusion Criteria:
- 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).
Sites / Locations
- 14 Sites
- 4 Sites
- 2 Sites
- 2 Sites
- 51 Sites
- 12 Sites
- 13 Sites
- 5 Sites
- 10 Sites
- 5 Sites
- 22 Sites
Arms of the Study
Arm 1
Arm 2
Arm Type
No Intervention
Other
Arm Label
Usual care
early standardised rhythm control
Arm Description
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.
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: Optimal antiarrhythmic drug therapy (Dronedarone, Amiodarone, Flecainide, Propafenone), Catheter ablation with the aim of pulmonary vein isolation (PVI), 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.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
The 2d outcome parameters are defined as
-all-cause death, AF-related death, time to the 1. occurrence of each of the components of the 1st co-primary outcome, time to recurrent AF (paroxysmal, persistent, long-lasting persistent, permanent) ,AF burden,time to 1. therapy change, time to 1. cv hosp., nr of cv hosp., left ventricular function at 24 months, QoL changes at 24 months and at study termination comp. to baseline, health-related cost calculation and cost of outpatient treatment, change of cognitive function at 24 months compared to BL, cardiac rhythm (sinus rhythm vs. AF), time to: -first symptomatic AF recurrence, -first progression of AF (from paroxysmal to persistent or long-lasting persistent or permanent and each of these components).
The 1st safety outcome:all deaths, the components of the 1st efficacy parameter plus other AEs rel. to the study intervention with special emphasis on proarrhythmia and complications due to interventions.
Full Information
NCT ID
NCT01288352
First Posted
February 1, 2011
Last Updated
July 21, 2020
Sponsor
Atrial Fibrillation Network
Collaborators
Sanofi, Abbott, Deutsche Herzstiftung e.V., European Heart Rhythm Association (EHRA), BMBF (German Ministry for Science), Deutsches Zentrum für Herz-Kreislauf-Forschung (DZHK)
1. Study Identification
Unique Protocol Identification Number
NCT01288352
Brief Title
Early Treatment of Atrial Fibrillation for Stroke Prevention Trial
Acronym
EAST
Official Title
Early Therapy of Atrial Fibrillation for Stroke Prevention Trial (EAST).
Study Type
Interventional
2. Study Status
Record Verification Date
June 2020
Overall Recruitment Status
Completed
Study Start Date
July 1, 2011 (Actual)
Primary Completion Date
March 6, 2020 (Actual)
Study Completion Date
May 31, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Atrial Fibrillation Network
Collaborators
Sanofi, Abbott, Deutsche Herzstiftung e.V., European Heart Rhythm Association (EHRA), BMBF (German Ministry for Science), Deutsches Zentrum für Herz-Kreislauf-Forschung (DZHK)
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Atrial Fibrillation, Stroke
Keywords
early treatment, rhythm control, atrial fibrillation, cardiovascular complications
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
2789 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Usual care
Arm Type
No Intervention
Arm Description
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.
Arm Title
early standardised rhythm control
Arm Type
Other
Arm Description
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:
Optimal antiarrhythmic drug therapy (Dronedarone, Amiodarone, Flecainide, Propafenone),
Catheter ablation with the aim of pulmonary vein isolation (PVI),
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.
Intervention Type
Other
Intervention Name(s)
early standardised rhythm control
Intervention Description
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:
Optimal antiarrhythmic drug therapy
Catheter ablation with the aim of pulmonary vein isolation (PVI),
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.
Primary Outcome Measure Information:
Title
A composite of cardiovascular death, stroke and hospitalization due to worsening of heart failure or due to acute coronary syndrome.
Description
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.
Time Frame
8 years
Secondary Outcome Measure Information:
Title
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.
Description
The 2d outcome parameters are defined as
-all-cause death, AF-related death, time to the 1. occurrence of each of the components of the 1st co-primary outcome, time to recurrent AF (paroxysmal, persistent, long-lasting persistent, permanent) ,AF burden,time to 1. therapy change, time to 1. cv hosp., nr of cv hosp., left ventricular function at 24 months, QoL changes at 24 months and at study termination comp. to baseline, health-related cost calculation and cost of outpatient treatment, change of cognitive function at 24 months compared to BL, cardiac rhythm (sinus rhythm vs. AF), time to: -first symptomatic AF recurrence, -first progression of AF (from paroxysmal to persistent or long-lasting persistent or permanent and each of these components).
The 1st safety outcome:all deaths, the components of the 1st efficacy parameter plus other AEs rel. to the study intervention with special emphasis on proarrhythmia and complications due to interventions.
Time Frame
8 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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.
Provision of signed informed consent.
Age ≥ 18 years.
Exclusion Criteria:
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).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Paulus Kirchhof, MD
Organizational Affiliation
University of Birmingham Centre for Cardiovascular Sciences, Department of Cardiology, University Heart and Vascular Center UKE Hamburg, Hamburg, Germany
Official's Role
Principal Investigator
Facility Information:
Facility Name
14 Sites
City
Different
Country
Belgium
Facility Name
4 Sites
City
Different
Country
Czechia
Facility Name
2 Sites
City
Different
Country
Denmark
Facility Name
2 Sites
City
Different
Country
France
Facility Name
51 Sites
City
Different
Country
Germany
Facility Name
12 Sites
City
Different
Country
Italy
Facility Name
13 Sites
City
Different
Country
Netherlands
Facility Name
5 Sites
City
Different
Country
Poland
Facility Name
10 Sites
City
Different
Country
Spain
Facility Name
5 Sites
City
Different
Country
Switzerland
Facility Name
22 Sites
City
Different
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
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.
IPD Sharing Time Frame
We will make data available starting six months after the publication of the primary results for 5 years.
IPD Sharing 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.
Citations:
Citation
International Landmark EAST Study Inverstigates Treatment Options for Atrial Fibrillation
Results Reference
result
PubMed Identifier
36036648
Citation
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.
Results Reference
derived
PubMed Identifier
35968706
Citation
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.
Results Reference
derived
PubMed Identifier
35863844
Citation
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.
Results Reference
derived
PubMed Identifier
34447995
Citation
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.
Results Reference
derived
PubMed Identifier
34328366
Citation
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.
Results Reference
derived
PubMed Identifier
32865375
Citation
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.
Results Reference
derived
PubMed Identifier
24016492
Citation
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.
Results Reference
derived
Links:
URL
http://www.easttrial.org
Description
official web page for the EAST trial
Learn more about this trial
Early Treatment of Atrial Fibrillation for Stroke Prevention Trial
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