Early Treatment of Atrial Fibrillation for Stroke Prevention Trial

Phase 4

Completed

• Conditions: Atrial Fibrillation; Stroke
• Interventions: Other: early standardised rhythm control

• Registration Number: NCT01288352
• Lead Sponsor: Atrial Fibrillation Network

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2011-02-01
• Study First Submitted QC: 2011-02-01
• Study First Posted: 2011-02-02
• Study Start: 2011-07-01
• Primary Completion: 2020-03-06
• Study Completion: 2020-05-31
• Status Verified: 2020-06
• Last Update Submitted: 2020-07-21
• Last Update Posted: 2020-07-23

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 2789

Inclusion Criteria

1. Recent-onset AF (≤ 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 sec.

3. 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.

4. Provision of signed informed consent.

5. Age ≥ 18 years.

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 randomized.
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).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
early standardised rhythm control	early standardised rhythm control	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.

Primary Outcome Measures

Name	Time	Method
A composite of cardiovascular death, stroke and hospitalization due to worsening of heart failure or due to acute coronary syndrome.	8 years	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

Name	Time	Method
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	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.

Trial Locations

Locations (9)

14 Sites; 🇧🇪 Different, Belgium

4 Sites; 🇨🇿 Different, Czechia

12 Sites; 🇮🇹 Different, Italy

51 Sites; 🇩🇪 Different, Germany

2 Sites; 🇫🇷 Different, France

10 Sites; 🇪🇸 Different, Spain

22 Sites; 🇬🇧 Different, United Kingdom

13 Sites; 🇳🇱 Different, Netherlands

5 Sites; 🇨🇭 Different, Switzerland