Skip to main content
OpenTrials
Recruiting

NCT Number: NCT03642509

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

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).

Recruiting

Interested in participating?

Request Info

Key information

Conditions

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

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Aarhus University Hospital, Aarhus, Central Jutland, Denmark

Loading trial locations.

About this study

An investigator-initiated multicenter, randomized open-label non-inferiority trial with blinded outcome evaluation (PROBE design). The active comparison LAAO is tested against NOAC therapy in a 1:1 stratified randomization. Patients should have AF, and an ischemic stroke or TIA within 6 months prior to enrollment. In total 750 patients will be included. Follow-up will be based on in-office and telephone follow-up during the first 3 years after randomization, along with up to 10 years long-term follow-up through the National Patient Registries.

The main study outcomes: The primary outcome is a composite of stroke (hemorrhagic or ischemic), systemic embolism, major bleeding or all-cause mortality assessed after at least two years follow-up for the last enrolled patient. Secondary outcomes will examine early and late safety outcome measures. The long-term outcome will be assessed up to 10-years after randomization through the National Patient Registries.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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)

Exclusion criteria

  • 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.

Treatment and study plan

Left Atrial Appendage Occlusion

Device

Interventional left atrial appendage occlusion with the Amulet or Watchman device

Other names: Left atrial appendage closure

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.

Other names: Edoxaban, Apixaban, Rivaroxaban, Dabigatran

Primary outcomes

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

    Time frame: Up to 5-years from randomization

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

Secondary outcomes

  1. Incidence of ischemic stroke

    Time frame: 2-, 3-, 5- and 10-years

    The occurrence of an acute onset of a focal neurological deficit of presumed vascular origin lasting for ≥ 24 hours or resulting in death. Stroke is categorized as ischemic based on computed tomography (CT) or magnetic resonance imaging (MRI) of the brain or autopsy.

  2. Incidence of hemorrhagic stroke

    Time frame: 2-, 3-, 5- and 10-years

    The occurrence of an acute onset of a focal neurological deficit of presumed vascular origin lasting for ≥ 24 hours or resulting in death. Stroke is categorized as hemorrhagic based on computed tomography (CT) or magnetic resonance imaging (MRI) of the brain or autopsy.

  3. Incidence of systemic embolism

    Time frame: 2-, 3-, 5- and 10-years

    The occurrence of an acute vascular insufficiency or occlusion of the extremities or any non-CNS organ associated with clinical, imaging, surgical or autopsy evidence of arterial occlusion in the absence of other likely mechanism (e.g. trauma, atherosclerosis, or instrumentation).

  4. Incidence of major or life-threatening bleeding

    Time frame: 2-, 3-, 5- and 10-years

    The occurrence of an overt bleeding associated with one or more of the following: decrease in hemoglobin of at least 3.0 g/dL, transfusion of 2 or more units of blood, causing hospitalization, requiring surgery, causing discontinuation of all antithrombotic therapy or pericardial bleeding with/without tamponade or occurring during the index LAAO procedure or during hospitalization for the index procedure (major bleeding). Life-threatening bleeding is defined as fatal bleeding, causing hypovolaemic shock or severe hypotension requiring vasopressor therapy or intervention, symptomatic bleeding in a critical organ (intracranial, intraspinal, intraocular, intramuscular with compartment syndrome, pericardial bleeding after hospitalization for the index LAAO) or overt bleeding with decrease in hemoglobin ≥ 5 g/dL or requiring transfusion of ≥ 4 units of blood.

  5. Incidence of all-cause mortality

    Time frame: 2-, 3-, 5- and 10-years

    The occurrence of death from any cause

  6. Incidence of Transient ischemic attack (TIA)

    Time frame: 2-, 3-, 5- and 10-years

    an episode of neurological dysfunction caused by focal brain, spinal cord or retinal ischemia leading to symptoms lasting less than 24 hours, without acute infarction based on neuroimaging.

  7. Number of patients with a device-related complication

    Time frame: 2 months

    A complication related to the presence of the device. Device-related complications include:

    • Device embolization
    • Device erosion
    • Clinically significant device interference with surrounding structures. This includes structures at the implant location (circumflex coronary artery, mitral valve, pulmonary artery, pulmonary vein) or cardiovascular structures in the vicinity of the location to which the device migrated (if applicable).
    • Device thrombus
    • Device fracture
    • Device infection/endocarditis/pericarditis
    • Device perforation/laceration
    • Device allergy

  8. Number of patients with a procedure-related complication

    Time frame: 2 months

    All complications related to the LAAO-procedure will be assessed.

  9. Number of patients with a device success

    Time frame: 2 months

    Device deployed and implanted in correct position

  10. Number of patients with technical success

    Time frame: 2 Months

    Exclusion of the left atrial appendage (LAA) achieved without device-related complications and no leak >5 mm on color Doppler TEE.

  11. Number of patients with procedural success

    Time frame: 2 months

    Technical success and no procedure-related complications, except uncomplicated device embolization (i.e. device embolization resolved by percutaneous retrieval during the procedure without surgical intervention or damage to surrounding cardiovascular structures).

  12. Number of patients with peri-device leaks at follow-up imaging

    Time frame: 2 months

    Detection of any peri-device flow/gap at follow-up cardiac CT/TEE.

  13. Changes in functional status based on Modified Rankin Scale

    Time frame: 24 months

    The Modified Rankin scale is used to measure the degree of disability or dependence in daily activities caused by a stroke. The scale runs from 0-6, from no symptoms (0) to death (6).

  14. Changes in Quality of life

    Time frame: 12 months

    Based on patient self-reported EuroQol-5D questionnaires. The EuroQol-5D is a standardized instrument to measure health-related quality of life. It includes five self-rated dimensions of mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The questionnaire have 3 levels of severity for each of the five dimensions. It also includes a visual scale from 0 (worst thinkable health condition) to 100 (best thinkable health condition) to report an overall measure.

  15. Compliance to NOAC

    Time frame: 2-, 3-, 5-, and 10-years

    Adherence to assigned NOAC therapy will be assessed through the National Prescription Registries.

  16. Changes in neurological status based on National Institute of Health (NIH) Stroke scale score

    Time frame: 12 months

    Assessed by the NIH stroke scale at baseline and 12 month follow-up. A scale to quantify the neurological impairment caused by a stroke. It includes 11 items, each of which scores a specific ability between 0 to 4. For each item, a score of 0 typically indicates normal function in that specific ability, while a higher score is indicative of some level of impairment. The individual scores are summed to calculate the total NIH Stroke Scale score, that can range from 0 to 42, with 0 being no symptoms.

    • Score 0: No stroke symptoms
    • Score 1-4: Minor stroke
    • Score 5-15: Moderate stroke
    • Score 16-20: Moderate to severe stroke
    • Score 21-42: Severe stroke

Other outcomes

  1. Minor bleeding

    Time frame: 24 months

    Any bleeding clinically mentionable that does not qualify as life-threatening, disabling or major.

  2. Comparison of the cost-effectiveness of LAAO and NOAC therapy

    Time frame: 24 months

    All costs and cost-effectiveness will be evaluated and compared between the two diagnostic strategies.

Study contacts

Contact information is provided by the study sponsor or research team.

Kasper Korsholm, MD

CONTACT

[email protected]

004578452254

Sponsors and collaborators

Lead sponsor

University of Aarhus

Other

Collaborators

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

Registry information

Official study title

Left Atrial Appendage Occlusion Versus Novel Oral Anticoagulation for Stroke Prevention in Atrial Fibrillation. A Multicenter Randomized Clinical Trial. (Occlusion-AF)

Acronym: Occlusion-AF

Important dates

Study start
2019
Primary completion
2026
Study completion
2030
First posted
Aug 22, 2018
Registry last updated
Dec 21, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.