Clinical trial NCT06324188: Early Atrial Fibrillation Ablation for Stroke Prevention in Patients with High Comorbidity Burden (EASThigh-AFNET 11)
Official title: Early Atrial Fibrillation Ablation for Stroke Prevention in Patients with High Comorbidity Burden (EASThigh-AFNET 11)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Atrial Fibrillation
Keywords: Early atrial fibrillation ablation
High comorbidity burden
CHA2DS2-VASc score
Early rhythm control
Stroke
Heart failure
Cardiovascular death
Cryoballoon
Lead sponsor: Atrial Fibrillation Network
Sponsor class: OTHER
First posted: 2024-03-21
Enrollment: 2312
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: 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.

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).

Eligibility criteria: Inclusion Criteria:

I1. AF first diagnosed within 2 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 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.

Primary outcomes:
measure: Composite of cardiovascular complications related to AF
timeFrame: Throughout study completion, estimated at a mean of 4 years
measure: The primary safety outcome is a composite of all-cause death and serious complications of AF therapy.
timeFrame: Throughout study completion, estimated at a mean of 4 years
Secondary outcomes:
measure: Number of nights spent in hospital
timeFrame: Throughout study completion, estimated at a mean of 4 years
measure: Time from randomisation to first occurrence of each of the individual components of the primary outcome
timeFrame: Throughout study completion, estimated at a mean of 4 years
measure: All-cause death
timeFrame: Throughout study completion, estimated at a mean of 4 years
measure: Serious adverse events related to AF therapy
timeFrame: Throughout study completion, estimated at a mean of 4 years
measure: Time from randomisation to first cardiovascular hospitalisation
timeFrame: Throughout study completion, estimated at a mean of 4 years
measure: Number of cardiovascular hospitalisations (over-night stay)
timeFrame: Throughout study completion, estimated at a mean of 4 years
measure: Changes in left ventricular ejection fraction
timeFrame: comparing baseline with 24 months follow up (FU)
measure: Changes in quality of life
timeFrame: comparing baseline with 12 and 24 months FU
measure: Changes in quality of life
timeFrame: comparing baseline with 12 and 24 months FU
measure: Changes in cognitive function
timeFrame: comparing baseline with 24 months FU
measure: Cardiac rhythm status
timeFrame: at 12 and 24 months FU
measure: AF pattern
timeFrame: at 12 and 24 months FU
measure: Time from randomisation to first clinical recurrence of AF
timeFrame: Throughout study completion, estimated at a mean of 4 years
measure: Time from randomisation to first progression of AF
timeFrame: Throughout study completion, estimated at a mean of 4 years
Other outcomes:
Locations:
city: Multiple Locations
country: Australia
facility: Several sites
city: Multiple Locations
country: Canada
facility: Several sites
city: Multiple Locations
country: Germany
facility: Several sites
city: Multiple Locations
country: Netherlands
facility: Several sites
city: Multiple Locations
country: United Kingdom
facility: Several sites
Study officials:
affiliation: University Heart and Vascular Center Hamburg, University Hospital Hamburg Eppendorf
name: Paulus Kirchhof, Prof. Dr.
role: STUDY_DIRECTOR
affiliation: University Heart and Vascular Center Hamburg, University Hospital Hamburg Eppendorf
name: Andreas Rillig, PD Dr.
role: STUDY_DIRECTOR
affiliation: University of British Columbia, Vancouver General Hospital, Department of Electrophysiology
name: Jason Andrade, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Cardiovascular Sciences, University of Leicester
name: André Ng, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Centre for Heart Rhythm Disorders, University of Adelaide, Royal Adelaide Hospital
name: Prash Sanders, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Patient representative
name: Volker Straub
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Cardiology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Center (MUMC)
name: Kevin Vernooy, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Institute of Medical Biometry and Epidemiology, University Medical Center Hamburg-Eppendorf
name: Antonia Zapf, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References:
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: 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: 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: Andrade JG, Wells GA, Deyell MW, Bennett M, Essebag V, Champagne J, Roux JF, Yung D, Skanes A, Khaykin Y, Morillo C, Jolly U, Novak P, Lockwood E, Amit G, Angaran P, Sapp J, Wardell S, Lauck S, Macle L, Verma A; EARLY-AF Investigators. Cryoablation or Drug Therapy for Initial Treatment of Atrial Fibrillation. N Engl J Med. 2021 Jan 28;384(4):305-315. doi: 10.1056/NEJMoa2029980. Epub 2020 Nov 16.
citation: Andrade JG, Deyell MW, Macle L, Wells GA, Bennett M, Essebag V, Champagne J, Roux JF, Yung D, Skanes A, Khaykin Y, Morillo C, Jolly U, Novak P, Lockwood E, Amit G, Angaran P, Sapp J, Wardell S, Lauck S, Cadrin-Tourigny J, Kochhauser S, Verma A; EARLY-AF Investigators. Progression of Atrial Fibrillation after Cryoablation or Drug Therapy. N Engl J Med. 2023 Jan 12;388(2):105-116. doi: 10.1056/NEJMoa2212540. Epub 2022 Nov 7.
citation: Dickow J, Kirchhof P, Van Houten HK, Sangaralingham LR, Dinshaw LHW, Friedman PA, Packer DL, Noseworthy PA, Yao X. Generalizability of the EAST-AFNET 4 Trial: Assessing Outcomes of Early Rhythm-Control Therapy in Patients With Atrial Fibrillation. J Am Heart Assoc. 2022 Jun 7;11(11):e024214. doi: 10.1161/JAHA.121.024214. Epub 2022 May 27.
citation: Dickow J, Kany S, Roth Cardoso V, Ellinor PT, Gkoutos GV, Van Houten HK, Kirchhof P, Metzner A, Noseworthy PA, Yao X, Rillig A. Outcomes of Early Rhythm Control Therapy in Patients With Atrial Fibrillation and a High Comorbidity Burden in Large Real-World Cohorts. Circ Arrhythm Electrophysiol. 2023 May;16(5):e011585. doi: 10.1161/CIRCEP.122.011585. Epub 2023 Mar 21.