Clinical trial NCT01288352: Early Treatment of Atrial Fibrillation for Stroke Prevention Trial
Official title: Early Therapy of Atrial Fibrillation for Stroke Prevention Trial (EAST).
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Atrial Fibrillation
Stroke
Keywords: early treatment
rhythm control
atrial fibrillation
cardiovascular complications
Lead sponsor: Atrial Fibrillation Network
Sponsor class: OTHER
Collaborators: name: Sanofi
name: Abbott
name: The German Heart Foundation
name: European Heart Rhythm Association (EHRA)
name: BMBF (German Ministry for Science)
name: Deutsches Zentrum für Herz-Kreislauf-Forschung (DZHK)
First posted: 2011-02-02
Enrollment: 2789
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.


Eligibility criteria: 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).

Primary outcomes:
measure: A composite of cardiovascular death, stroke and hospitalization due to worsening of heart failure or due to acute coronary syndrome.
timeFrame: 8 years
Secondary outcomes:
measure: 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.
timeFrame: 8 years
Other outcomes:
Locations:
city: Different
country: Belgium
facility: 14 Sites
city: Different
country: Czechia
facility: 4 Sites
city: Different
country: Denmark
facility: 2 Sites
city: Different
country: France
facility: 2 Sites
city: Different
country: Germany
facility: 51 Sites
city: Different
country: Italy
facility: 12 Sites
city: Different
country: Netherlands
facility: 13 Sites
city: Different
country: Poland
facility: 5 Sites
city: Different
country: Spain
facility: 10 Sites
city: Different
country: Switzerland
facility: 5 Sites
city: Different
country: United Kingdom
facility: 22 Sites
Study officials:
affiliation: University of Birmingham Centre for Cardiovascular Sciences, Department of Cardiology, University Heart and Vascular Center UKE Hamburg, Hamburg, Germany
name: Paulus Kirchhof, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: International Landmark EAST Study Inverstigates Treatment Options for Atrial Fibrillation
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.
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.
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.
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.
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.
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.
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.