Early treatment of atrial fibrillation for stroke prevention trial
| ISRCTN | ISRCTN04708680 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN04708680 |
| EudraCT/CTIS number | 2010-021258-20 |
| ClinicalTrials.gov number | NCT01288352 |
- Submission date
- 07/12/2010
- Registration date
- 10/01/2011
- Last edited
- 07/05/2024
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Circulatory System
Plain English Summary
Current plain English summary as of 19/08/2020:
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 May 2020 (updated 19/08/2020, previously: December 2019)
Who is funding the study?
German Atrial Fibrillation Network (Germany)
Sanofi (Germany)
Abbot (Germany)
Deutsche Herzstiftung e.V. (Germany)
European Heart rhythm Association (EHRA)
BMBF (German Ministry for Science)
Deutsches Zentrum für Herz-Kreislauf-forschung (DZHK) (Germany)
Who is the main contact?
Prof Paulus Kirchhof
Previous 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, east@cri-muc.eu
Contact information
Scientific
University Heart and Vascular Center UKE, Department of Cardiology
Martinistraße 52, Gebäude Ost 70
Hamburg
20246
Germany
Study information
| Study design | Phase IV randomized open prospective two-armed parallel-group multicentre trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised parallel trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details to request a patient information sheet |
| 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 |
| Study acronym | EAST-AFNET 4 |
| 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(s) | Ethikkommission der Ärztekammer Westfalen-Lippe und der Medizinischen Fakultät der Westfälischen Wilhelms-Universität Münster, 09/02/2011, ref: 2010-274-f-A |
| 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 |
| Pharmaceutical study type(s) | |
| Phase | Phase IV |
| Drug / device / biological / vaccine name(s) | Not provided at time of registration |
| Primary outcome measure | 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 study start date | 01/07/2011 |
| Overall study end date | 29/05/2020 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 2745 (first patient in on 28/07/2011) |
| Total final enrolment | 2789 |
| 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 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
Study participating centre
80335
Germany
Sponsor information
Research organisation
Mendelstr. 11
Münster
48149
Germany
| Website | http://www.kompetenznetz-vorhofflimmern.de |
|---|---|
"ROR" |
https://ror.org/01spm3d88 |
Funders
Funder type
Research organisation
No information available
Government organisation / For-profit companies (industry)
- Alternative name(s)
- sanofi-aventis, Sanofi US, Sanofi-Aventis U.S. LLC, Sanofi U.S.
- Location
- United States of America
Private sector organisation / For-profit companies (industry)
- Location
- United States of America
No information available
No information available
No information available
No information available
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan | Not provided at time of registration |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol article | protocol | 01/11/2011 | Yes | No | |
| Other publications | rationale and design | 01/09/2013 | Yes | No | |
| Other publications | article | 01/02/2015 | Yes | No | |
| Results article | results | 01/10/2020 | 02/09/2020 | Yes | No |
| Results article | Subanalysis of patients with heart failure | 30/07/2021 | 02/08/2021 | Yes | No |
| Results article | Subanalysis in asymptomatic patients | 27/08/2021 | 31/08/2021 | Yes | No |
| Results article | Analysis of treatment patterns | 02/09/2021 | 03/09/2021 | Yes | No |
| Results article | Association between pattern of atrial fibrillation and outcomes | 26/07/2022 | 22/07/2022 | Yes | No |
| Results article | 15/08/2022 | 16/08/2022 | Yes | No | |
| Results article | Early rhythm control | 29/08/2022 | 30/08/2022 | Yes | No |
| Results article | subgroup analysis for early rhythm-control therapy | 01/01/2023 | 16/12/2022 | Yes | No |
| Results article | Association of genetic risk and outcomes in patients with atrial fibrillation: interactions with early rhythm control in the EAST-AFNET4 trial | 02/06/2023 | 02/06/2023 | Yes | No |
| Results article | Safety and efficacy of long-term sodium channel blocker therapy for early rhythm control | 04/05/2024 | 07/05/2024 | Yes | No |
Editorial Notes
07/05/2024: Publication reference added.
02/06/2023: Publication reference added.
16/12/2022: Publication reference added.
30/08/2022: Publication reference added.
16/08/2022: Publication reference added.
22/07/2022: Publication reference added.
03/09/2021: Publication reference added.
31/08/2021: Publication reference added.
02/08/2021: Publication reference added.
16/12/2020: The following changes have been made:
1. The overall trial end date has been changed from 31/05/2020 to 29/05/2020.
2. An additional trial website has been added.
3. The scientific contact's details have been updated.
02/09/2020: Publication reference and total final enrolment number added.
19/08/2020: The following changes were made to the trial record:
1. The funders "Sanofi, Abbot, Deutsche Herzstiftung e.V., European Heart rhythm Association (EHRA), BMBF (German Ministry for Science), Deutsches Zentrum für Herz-Kreislauf-forschung (DZHK)" were added.
2. The acronym was changed from "EAST" to "EAST-AFNET 4".
3. The overall end date was changed from 01/12/2019 to 31/05/2020.
4. The plain English summary was updated to reflect these changes.
09/08/2019: Internal review.
16/03/2016: Plain English summary added.
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.
