Early Atrial Fibrillation Ablation for Stroke Prevention in Patients With High Comorbidity Burden (EASThigh-AFNET 11)

January 6, 2026 updated by: Atrial Fibrillation Network

EASThigh-AFNET 11 is an international, prospective, randomized, open, blinded endpoint assessment, multicenter trial (Treatment Strategy trial).

The objective of EASThigh-AFNET 11 is to investigate whether early atrial fibrillation ablation in patients with atrial fibrillation (AF) and a high comorbidity burden (CHA2DS2-VASc ≥4) reduces cardiovascular events (stroke, cardiovascular death, or heart failure events) compared to usual care.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Atrial Fibrillation (AF) is associated with high morbidity and mortality. Even on optimal anticoagulation and therapy of concomitant conditions, many patients with AF suffer cardiovascular events, especially heart failure events, stroke, and cardiovascular death. Most of these events occur in elderly patients with comorbidities. Early rhythm control, mainly delivered using antiarrhythmic drugs, reduces AF-related complications when added to anticoagulation, rate control, and treatment of comorbidities when compared to current practice that offers rhythm control mainly to reduce symptoms. The outcome-reducing effect of early rhythm control is most pronounced in patients with multiple comorbidities, quantified by a CHA2DS2-VASc score ≥ 4. Attaining sinus rhythm is the key mediator for the outcome-reducing effect of early rhythm control. Atrial fibrillation ablation controls the rhythm better than drug-based rhythm control, avoids long-term antiarrhythmic drug treatment, thus reducing polypharmacy, and may therefore be the ideal rhythm control treatment in patients with AF and a high comorbidity burden. This hypothesis needs testing. The investigator-initiated EASThigh-AFNET 11 trial evaluates the effectiveness and safety of early atrial fibrillation ablation in patients with recently diagnosed AF and a high comorbidity burden.

EASThigh-AFNET 11 is a Treatment Strategy trial randomizing 2312 patients with AF and a high comorbidity burden to early atrial fibrillation ablation or usual care to achieve a fixed number of primary endpoint events of n=527. All therapies are clinically approved. The primary outcome is a composite of cardiovascular death, stroke, and hospitalization for worsening of heart failure. The primary safety outcome is a composite of all-cause death and serious complications of AF therapy. Secondary outcome parameters address safety, patient reported outcomes and cognitive function.

EASThigh-AFNET 11 was recommended for funding by the Expert Advisory Panel of the Global Cardiovascular Research Funders Forum (GCRFF).

Study Type

Interventional

Enrollment (Estimated)

2312

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Australia
      • Multiple Locations, Australia
        • Not yet recruiting
        • Several sites
  • Canada
      • Multiple Locations, Canada
        • Recruiting
        • Several sites
  • Germany
      • Multiple Locations, Germany
        • Recruiting
        • Several sites
  • Netherlands
      • Multiple Locations, Netherlands
        • Recruiting
        • Several sites
  • Poland
      • Multiple Locations, Poland
        • Recruiting
        • Several sites
  • Spain
      • Multiple Locations, Spain
        • Recruiting
        • Several sites
  • United Kingdom
      • Multiple Locations, United Kingdom
        • Not yet recruiting
        • Several sites

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

I1. AF first diagnosed within 5 years prior to enrolment and documented in body surface ECG

I2. High comorbidity estimated by CHA2DS2-VASc score of 4 or more

I3. Patient suitable for ablation using cryoballoon ablation systems or other ablation systems with comparable efficacy and safety from Medtronic

I4. Age ≥ 18 years

I5. Provision of signed informed consent

Exclusion Criteria:

General exclusion criteria

E1. Any disease that limits life expectancy to less than 1 year.

E2. Participation in another clinical trial, either within the 3 months prior to enrolment or still on-going (participation in potential sub-studies connected to this trial is permitted).

E3. Previous participation in EASThigh-AFNET 11.

E4. Pregnant women.

E5. Breastfeeding women.

E6. Drug abuse or clinically manifest alcohol abuse.

Exclusion criteria related to a cardiac condition

E7. Prior AF ablation or surgical therapy of AF.

E8. Patients not suitable for AF ablation.

E9. Patients with a history of stroke which occurred within 3 months prior to enrolment.

E10. Valve disease requiring specific therapy.

Exclusion criteria based on laboratory abnormalities

E11. Clinically manifested thyroid dysfunction requiring therapy.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: Usual Care
Other: Usual Care
Usual care will consist of optimal AF therapy based on guideline recommendations and local protocols and usage.The choice of therapies and medications follows routine care in line with medical guidelines and local policies at the discretion of the treating physician and should be based on the individual medical status of each study patient.
Other: Early atrial fibrillation ablation
Other: Early atrial fibrillation ablation
Patients randomised to early atrial fibrillation ablation will undergo pulmonary vein isolation within 2 months after randomisation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Composite of cardiovascular complications related to AF
Time Frame: Throughout study completion, estimated at a mean of 4 years
It is defined as time from randomisation to the first occurrence of a composite of cardiovascular death, stroke (either ischemic or hemorrhagic), or hospitalisation for worsening of heart failure.
Throughout study completion, estimated at a mean of 4 years
The primary safety outcome is a composite of all-cause death and serious complications of AF therapy.
Time Frame: Throughout study completion, estimated at a mean of 4 years
Serious Adverse Events (SAEs), including primary and secondary outcome parameters if based on clinical events, will be adjudicated by the independent Clinical Event Committee (CEC) according to standardised definitions given in the CEC charter.
Throughout study completion, estimated at a mean of 4 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of nights spent in hospital
Time Frame: Throughout study completion, estimated at a mean of 4 years
Throughout study completion, estimated at a mean of 4 years
Time from randomisation to first occurrence of each of the individual components of the primary outcome
Time Frame: Throughout study completion, estimated at a mean of 4 years
Throughout study completion, estimated at a mean of 4 years
All-cause death
Time Frame: Throughout study completion, estimated at a mean of 4 years
Throughout study completion, estimated at a mean of 4 years
Serious adverse events related to AF therapy
Time Frame: Throughout study completion, estimated at a mean of 4 years
Throughout study completion, estimated at a mean of 4 years
Time from randomisation to first cardiovascular hospitalisation
Time Frame: Throughout study completion, estimated at a mean of 4 years
Throughout study completion, estimated at a mean of 4 years
Number of cardiovascular hospitalisations (over-night stay)
Time Frame: Throughout study completion, estimated at a mean of 4 years
Throughout study completion, estimated at a mean of 4 years
Changes in left ventricular ejection fraction
Time Frame: comparing baseline with 24 months follow up (FU)
comparing baseline with 24 months follow up (FU)
Changes in quality of life
Time Frame: comparing baseline with 12 and 24 months FU
assessed by EQ-5D-5L
comparing baseline with 12 and 24 months FU
Changes in quality of life
Time Frame: comparing baseline with 12 and 24 months FU
assessed by AFEQT
comparing baseline with 12 and 24 months FU
Changes in cognitive function
Time Frame: comparing baseline with 24 months FU
assessed by Montreal-Cognitive-Assessment-Test
comparing baseline with 24 months FU
Cardiac rhythm status
Time Frame: at 12 and 24 months FU
sinus rhythm compared to AF
at 12 and 24 months FU
AF pattern
Time Frame: at 12 and 24 months FU
at 12 and 24 months FU
Time from randomisation to first clinical recurrence of AF
Time Frame: Throughout study completion, estimated at a mean of 4 years
Throughout study completion, estimated at a mean of 4 years
Time from randomisation to first progression of AF
Time Frame: Throughout study completion, estimated at a mean of 4 years
i. e. from paroxysmal to persistent or longstanding persistent or permanent and each of these components
Throughout study completion, estimated at a mean of 4 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Atrial Fibrillation Network

Investigators

  • Study Director: Paulus Kirchhof, Prof. Dr., University Heart and Vascular Center Hamburg, University Hospital Hamburg Eppendorf
  • Study Director: Andreas Rillig, PD Dr., University Heart and Vascular Center Hamburg, University Hospital Hamburg Eppendorf
  • Principal Investigator: Jason Andrade, Prof. Dr., University of British Columbia, Vancouver General Hospital, Department of Electrophysiology
  • Principal Investigator: André Ng, Prof. Dr., Department of Cardiovascular Sciences, University of Leicester
  • Principal Investigator: Prash Sanders, Prof. Dr., Centre for Heart Rhythm Disorders, University of Adelaide, Royal Adelaide Hospital
  • Principal Investigator: Volker Straub, Patient representative
  • Principal Investigator: Kevin Vernooy, Prof. Dr., Department of Cardiology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Center (MUMC)
  • Principal Investigator: Antonia Zapf, Prof. Dr., Institute of Medical Biometry and Epidemiology, University Medical Center Hamburg-Eppendorf

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 14, 2024

Primary Completion (Estimated)

February 1, 2030

Study Completion (Estimated)

May 1, 2030

Study Registration Dates

First Submitted

March 4, 2024

First Submitted That Met QC Criteria

March 19, 2024

First Posted (Actual)

March 21, 2024

Study Record Updates

Last Update Posted (Actual)

January 8, 2026

Last Update Submitted That Met QC Criteria

January 6, 2026

Last Verified

November 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • EASThigh-AFNET 11

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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