Left Atrial Appendage Occlusion Versus Novel Oral Anticoagulation for Stroke Prevention in Atrial Fibrillation (Occlusion-AF)

December 15, 2023 updated by: University of Aarhus

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

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).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Estimated)

750

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 Locations

  • Denmark
      • Copenhagen, Denmark
        • Not yet recruiting
        • Rigshospitalet
        • Contact:
          • Ole de Backer
      • Holstebro, Denmark
        • Recruiting
        • Regional Hospital West Jutland
        • Contact:
          • Mohammad Al-Jazi, MD
    • Central Denmark Region
      • Aarhus, Central Denmark Region, Denmark, 8200
        • Recruiting
        • Aarhus University Hospital
        • Contact:
        • Contact:
          • Jens Erik Nielsen-Kudsk, MD DMSc Prof
          • Phone Number: 0078452024
          • Email: jensnils@rm.dk
    • Region Of Southern Denmark
      • Odense, Region Of Southern Denmark, Denmark, 5000
        • Active, not recruiting
        • Odense University Hospital
    • The North Denmark Region
      • Aalborg, The North Denmark Region, Denmark, 9000
        • Recruiting
        • Aalborg University Hospital
        • Contact:
          • Boris Modrau, MD, PhD
  • Finland
      • Helsinki, Finland
        • Recruiting
        • Helsinki University Central Hospital
        • Contact:
          • Juha Sinisalo, MD, PhD
      • Oulu, Finland
        • Withdrawn
        • Oulu University Hospital
      • Turku, Finland, 20521
        • Not yet recruiting
        • Turku University Hospital
        • Contact:
          • Juha Lund, MD
  • Germany
      • Jena, Germany
        • Recruiting
        • Jena University Hospital
        • Contact:
          • Günther Albrecht
  • Norway
      • Bergen, Norway, 5021
        • Recruiting
        • Haukeland University Hospital
        • Contact:
          • Erik JS Packer, MD
      • Oslo, Norway
        • Recruiting
        • Oslo University Hospital
        • Contact:
          • Anne Hege Aamodt, MD, PhD
      • Trondheim, Norway
        • Not yet recruiting
        • Trondheim University Hospital
        • Contact:
          • Hanne Ellekjær
  • Sweden
      • Göteborg, Sweden, 41345
        • Recruiting
        • Sahlgrenska University Hospital
        • Contact:
          • Jacob Odenstedt, MD, PhD
      • Lund, Sweden
        • Not yet recruiting
        • Skånes University Hospital
        • Contact:
          • Arne Lindgren
      • Stockholm, Sweden, 17176
        • Recruiting
        • Karolinska University Hospital
        • Contact:
          • Nikola Drca, MD, PhD
        • Principal Investigator:
          • Per Wester, MD, PhD

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

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

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
Experimental: LAAO group
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
Interventional left atrial appendage occlusion with the Amulet or Watchman device
Other Names:
  • Left atrial appendage closure
Experimental: NOAC group
Patients will be treated with one of the currently available NOAC drugs; Apixaban, Dabigatran, Edoxaban or Rivaroxaban.
Drug: NOAC
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:
  • Apixaban
  • Dabigatran
  • Edoxaban
  • Rivaroxaban

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Up to 5-years from randomization

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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-, 3-, 5- and 10-years
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.
2-, 3-, 5- and 10-years
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).
2-, 3-, 5- and 10-years
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.
2-, 3-, 5- and 10-years
Incidence of all-cause mortality
Time Frame: 2-, 3-, 5- and 10-years
The occurrence of death from any cause
2-, 3-, 5- and 10-years
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.
2-, 3-, 5- and 10-years
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
2 months
Number of patients with a procedure-related complication
Time Frame: 2 months
All complications related to the LAAO-procedure will be assessed.
2 months
Number of patients with a device success
Time Frame: 2 months
Device deployed and implanted in correct position
2 months
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.
2 Months
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).
2 months
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.
2 months
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).
24 months
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.
12 months
Compliance to NOAC
Time Frame: 2-, 3-, 5-, and 10-years
Adherence to assigned NOAC therapy will be assessed through the National Prescription Registries.
2-, 3-, 5-, and 10-years
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
12 months

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Minor bleeding
Time Frame: 24 months
Any bleeding clinically mentionable that does not qualify as life-threatening, disabling or major.
24 months
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.
24 months

Collaborators and Investigators

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

Sponsor

University of Aarhus

Collaborators

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

Investigators

  • Study Chair: 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

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)

January 1, 2019

Primary Completion (Estimated)

January 1, 2026

Study Completion (Estimated)

October 1, 2030

Study Registration Dates

First Submitted

July 6, 2018

First Submitted That Met QC Criteria

August 21, 2018

First Posted (Actual)

August 22, 2018

Study Record Updates

Last Update Posted (Estimated)

December 21, 2023

Last Update Submitted That Met QC Criteria

December 15, 2023

Last Verified

December 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Occlusion-AF-AUH250418-32

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

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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