Left Atrial Appendage Occlusion Versus Novel Oral Anticoagulation for Stroke Prevention in Atrial Fibrillation

NCT03642509 | Recruiting DMC

• 1 other identifier: Occlusion-AF-AUH250418-32
• Study Type: interventional
• Target: 750
• Locations: 5 countries
• Sites: 15

Brief Summary

Atrial fibrillation (AF) is progressively common, and increases the risk of stroke five-fold. Oral anticoagulation is the mainstay therapy; however, it increases the risk of bleeding. Moreover, 30% with AF and at risk of stroke are not in relevant anticoagulation. The randomized PROTECT-AF trial has demonstrated the superiority of left atrial appendage occlusion (LAAO) as compared to warfarin for prevention of the combined endpoint of stroke, major bleeding and cardiovascular mortality. However, studies comparing LAAO to therapy with novel oral anticoagulants (NOAC) have not been carried out. This study aims to assess the effect of left atrial appendage occlusion (LAAO) to reduce the incidence of stroke, systemic embolism, major bleeding and all-cause mortality in patients with atrial fibrillation (AF) and a prior ischemic stroke or transient ischemic attack (TIA).

Conditions

Atrial Fibrillation; Stroke

Keywords

Left atrial appendage occlusion; Novel oral anticoagulation

Outcome Measures

Primary Outcomes (1)

• Composite endpoint of stroke (ischemic and hemorrhagic), systemic embolism, major bleeding and all-cause mortality.

  The primary endpoint is the combined rate of stroke, systemic embolism, major bleeding and all-cause mortality.

  Up to 5-years from randomization

Secondary Outcomes (16)

• Incidence of ischemic stroke

  2-, 3-, 5- and 10-years

• Incidence of hemorrhagic stroke

  2-, 3-, 5- and 10-years

• Incidence of systemic embolism

  2-, 3-, 5- and 10-years

• Incidence of major or life-threatening bleeding

  2-, 3-, 5- and 10-years

• Incidence of all-cause mortality

  2-, 3-, 5- and 10-years

Other Outcomes (2)

• Minor bleeding

  24 months

• Comparison of the cost-effectiveness of LAAO and NOAC therapy

  24 months

Study Arms (2)

LAAO group

EXPERIMENTAL

Patients will be treated with transcatheter left atrial appendage occlusion. The LAAO may be performed with the Amulet or Watchman device.

Device: Left atrial appendage occlusion

NOAC group

EXPERIMENTAL

Patients will be treated with one of the currently available NOAC drugs; Apixaban, Dabigatran, Edoxaban or Rivaroxaban.

Drug: NOAC

Interventions

Left atrial appendage occlusion DEVICE

Interventional left atrial appendage occlusion with the Amulet or Watchman device

Also known as: Left atrial appendage closure

LAAO group

NOAC DRUG

Medical treatment arm. Patients will be treated with one of the available NOAC drugs; Apixaban, Dabigatran, Edoxaban or Rivaroxaban. The specific drug and dose is at the discretion of the treating physician.

Also known as: Edoxaban, Apixaban, Rivaroxaban, Dabigatran

NOAC group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years
• documented non-valvular atrial fibrillation (paroxysmal, persistent or permanent)
• Eligible for long-term Novel Oral Anticoagulation (NOAC) therapy
• Ischemic stroke within the recent 6 months verified by neuroimaging, or
• Transient ischemic attack within 6 months with proven cerebral ischemia based on cerebral magnetic resonance imaging (MRI)

You may not qualify if:

• Modified rankin scale \> 3 at time of enrollment
• Glomerular filtration rate (GFR) below 15 ml/min/1.73 m2
• Contraindication towards long-term aspirin therapy
• Planned combined cardiovascular interventional procedures at the time of enrollment
• Terminal illness or cancer with life expectancy less than 2 years.

Sponsors & Collaborators

• University of Aarhus: lead
• Aarhus University Hospital: collaborator
• Aalborg University Hospital: collaborator
• Odense University Hospital: collaborator
• Sahlgrenska University Hospital: collaborator
• Karolinska University Hospital: collaborator
• Haukeland University Hospital: collaborator
• Helsinki University Central Hospital: collaborator
• Gødstrup Hospital: collaborator
• Lund University Hospital: collaborator
• Oslo University Hospital: collaborator
• Trondheim University Hospital: collaborator
• Rigshospitalet, Denmark: collaborator
• Jena University Hospital: collaborator

Study Sites (15)

Aarhus University Hospital

Aarhus, Central Jutland, 8200, Denmark

RECRUITING

Odense University Hospital

Odense, Region Syddanmark, 5000, Denmark

ACTIVE NOT RECRUITING

Aalborg University Hospital

Aalborg, The North Denmark Region, 9000, Denmark

RECRUITING

Rigshospitalet

Copenhagen, Denmark

NOT YET RECRUITING

Regional Hospital West Jutland

Holstebro, Denmark

RECRUITING

Helsinki University Central Hospital

Helsinki, Finland

RECRUITING

Oulu University Hospital

Oulu, Finland

WITHDRAWN

Turku University Hospital

Turku, 20521, Finland

NOT YET RECRUITING

Jena University Hospital

Jena, Germany

RECRUITING

Haukeland University Hospital

Bergen, 5021, Norway

RECRUITING

Oslo University Hospital

Oslo, Norway

RECRUITING

Trondheim University Hospital

Trondheim, Norway

NOT YET RECRUITING

Sahlgrenska University Hospital

Gothenburg, 41345, Sweden

RECRUITING

Skånes University Hospital

Lund, Sweden

NOT YET RECRUITING

Karolinska University Hospital

Stockholm, 17176, Sweden

RECRUITING

Related Publications (22)

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MeSH Terms

Conditions

Atrial Fibrillation; Stroke

Interventions

Left Atrial Appendage Closure; N(4)-oleylcytosine arabinoside; edoxaban; apixaban; Rivaroxaban; Dabigatran

Condition Hierarchy (Ancestors)

Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases

Intervention Hierarchy (Ancestors)

Cardiac Catheterization; Catheterization; Therapeutics; Investigative Techniques; Thiophenes; Sulfur Compounds; Organic Chemicals; Morpholines; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyridines; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Kasper Korsholm, MD

  Aarhus University Hospital

  STUDY CHAIR

• Jens Erik Nielsen-Kudsk, MD DMSc Prof

  Aarhus University Hospital

  STUDY CHAIR

• Dorte Damgaard, MD PhD

  Aarhus University Hospital

  STUDY CHAIR

• Søren Paaske Johnsen, MD PhD Prof

  Aalborg University Hospital

  STUDY CHAIR

Central Study Contacts

Kasper Korsholm, MD

CONTACT

004578452254; kasperkorsholm@clin.au.dk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Open-label study with blinded outcome assessment by an independent clinical event committee
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 6, 2018
• First Posted: August 22, 2018
• Study Start: January 1, 2019
• Primary Completion: January 1, 2026
• Study Completion (Estimated): October 1, 2030
• Last Updated: December 21, 2023

Record last verified: 2023-12

Locations

DE (1); FI (3); DK (5); SE (3); NO (3)