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

Atrial Fibrillation Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06324188
• Other study ID #: EASThigh-AFNET 11
• Status: Not yet recruiting
• Phase: N/A
• Start date: June 2024
• Est. completion date: May 2030

Study information

• Verified date: March 2024
• Source: Atrial Fibrillation Network
• Contact: Antje Albring, Dr.
• Phone: +49 251 980 1330
• Email: easthigh[@]af-net.eu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 2312
• Est. completion date: May 2030
• Est. primary completion date: February 2030
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Atrial Fibrillation

Intervention

Other:
• Early atrial fibrillation ablation
Patients randomised to early atrial fibrillation ablation will undergo pulmonary vein isolation within 2 months after randomisation.
• 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.

Locations

Country	Name	City	State
Australia	Several sites	Multiple Locations
Canada	Several sites	Multiple Locations
Germany	Several sites	Multiple Locations
Netherlands	Several sites	Multiple Locations
United Kingdom	Several sites	Multiple Locations

Sponsors (1)

Lead Sponsor	Collaborator
Atrial Fibrillation Network

Countries where clinical trial is conducted

Australia,  Canada,  Germany,  Netherlands,  United Kingdom, 

References & Publications (7)

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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Composite of cardiovascular complications related to AF	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
Primary	The primary safety outcome is a composite of all-cause death and serious complications of AF therapy.	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	Number of nights spent in hospital		Throughout study completion, estimated at a mean of 4 years
Secondary	Time from randomisation to first occurrence of each of the individual components of the primary outcome		Throughout study completion, estimated at a mean of 4 years
Secondary	All-cause death		Throughout study completion, estimated at a mean of 4 years
Secondary	Serious adverse events related to AF therapy		Throughout study completion, estimated at a mean of 4 years
Secondary	Time from randomisation to first cardiovascular hospitalisation		Throughout study completion, estimated at a mean of 4 years
Secondary	Number of cardiovascular hospitalisations (over-night stay)		Throughout study completion, estimated at a mean of 4 years
Secondary	Changes in left ventricular ejection fraction		comparing baseline with 24 months follow up (FU)
Secondary	Changes in quality of life	assessed by EQ-5D-5L	comparing baseline with 12 and 24 months FU
Secondary	Changes in quality of life	assessed by AFEQT	comparing baseline with 12 and 24 months FU
Secondary	Changes in cognitive function	assessed by Montreal-Cognitive-Assessment-Test	comparing baseline with 24 months FU
Secondary	Cardiac rhythm status	sinus rhythm compared to AF	at 12 and 24 months FU
Secondary	AF pattern		at 12 and 24 months FU
Secondary	Time from randomisation to first clinical recurrence of AF		Throughout study completion, estimated at a mean of 4 years
Secondary	Time from randomisation to first progression of AF	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