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Atrial FibrillationOcclusion-AFNCT03642509

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

A study testing Left atrial appendage occlusion and NOAC in people with Atrial Fibrillation and Stroke, run by University of Aarhus at 15 sites in 5 countries.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Atrial Fibrillation, Stroke
What is being tested?
Left atrial appendage occlusion and NOAC
Type of treatment
Medical device
Could I receive a placebo?
No, everyone receives an active treatment
How many people
750 participants
Where
15 sitesin 5 countries
Study dates
1 Jan 2019to 1 Oct 2030
Phase
Interventional
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)

Who cannot join

  • 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.

Trial locations and contacts

15 sites in 5 countries. Contact the study team or a site near you to ask about taking part.

Kasper Korsholm, MD contact

004578452254

kasperkorsholm@clin.au.dk

15 sites in 5 countries

Denmark5 sites, 4 recruiting

  • Aalborg University Hospital

    Aalborg, The North Denmark Region, 9000

    Boris Modrau, MD, PhD

    Recruiting

  • Aarhus University Hospital

    Aarhus, Central Jutland, 8200

    Kasper Korsholm, MD, 004578452254, kasperkorsholm@clin.au.dk

    Jens Erik Nielsen-Kudsk, MD DMSc Prof, 0078452024, jensnils@rm.dk

    Recruiting

  • Rigshospitalet

    Copenhagen

    Ole de Backer

    Not yet recruiting

  • Regional Hospital West Jutland

    Holstebro

    Mohammad Al-Jazi, MD

    Recruiting

  • Odense University Hospital

    Odense, Region Syddanmark, 5000

    Active, not recruiting

Other trials in Denmark

Finland3 sites, 2 recruiting

  • Helsinki University Central Hospital

    Helsinki

    Juha Sinisalo, MD, PhD

    Recruiting

  • Oulu University Hospital

    Oulu

    Withdrawn

  • Turku University Hospital

    Turku, 20521

    Juha Lund, MD

    Not yet recruiting

Other trials in Finland

Norway3 sites, 3 recruiting

  • Haukeland University Hospital

    Bergen, 5021

    Erik JS Packer, MD

    Recruiting

  • Oslo University Hospital

    Oslo

    Anne Hege Aamodt, MD, PhD

    Recruiting

  • Trondheim University Hospital

    Trondheim

    Hanne Ellekjær

    Not yet recruiting

Other trials in Norway

Sweden3 sites, 3 recruiting

  • Sahlgrenska University Hospital

    Gothenburg, 41345

    Jacob Odenstedt, MD, PhD

    Recruiting

  • Skånes University Hospital

    Lund

    Arne Lindgren

    Not yet recruiting

  • Karolinska University Hospital

    Stockholm, 17176

    Nikola Drca, MD, PhD

    Per Wester, MD, PhD

    Recruiting

Other trials in Sweden

Germany1 site, 1 recruiting

  • Jena University Hospital

    Jena

    Günther Albrecht

    Recruiting

Other trials in Germany

About this study

Official title: 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).

Read the 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.

Being tested
Left atrial appendage occlusion, NOAC
Keywords
Left atrial appendage occlusion, Novel oral anticoagulation
Medical subject headings
Atrial Fibrillation, Stroke

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Left atrial appendage occlusionDevice

    Also called Left atrial appendage closure

    Interventional left atrial appendage occlusion with the Amulet or Watchman device

  • NOACDrug

    Also called Edoxaban, Apixaban, Rivaroxaban, Dabigatran

    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.

Study groups in NCT03642509
Study groupRoleWhat they receive
LAAO groupExperimentalPatients will be treated with transcatheter left atrial appendage occlusion. The LAAO may be performed with the Amulet or Watchman device.
Receives: Device: Left atrial appendage occlusion
NOAC groupExperimentalPatients will be treated with one of the currently available NOAC drugs; Apixaban, Dabigatran, Edoxaban or Rivaroxaban.
Receives: Drug: NOAC

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Up to 5-years from randomization

Secondary outcomes (16)

  1. Incidence of ischemic stroke

    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.

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

  2. Incidence of hemorrhagic stroke

    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.

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

  3. Incidence of systemic embolism

    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).

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

  4. Incidence of major or life-threatening bleeding

    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.

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

  5. Incidence of all-cause mortality

    The occurrence of death from any cause

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

  6. Incidence of Transient ischemic attack (TIA)

    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.

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

  7. Number of patients with a device-related complication

    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

    Measured: 2 months

  8. Number of patients with a procedure-related complication

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

    Measured: 2 months

  9. Number of patients with a device success

    Device deployed and implanted in correct position

    Measured: 2 months

  10. Number of patients with technical success

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

    Measured: 2 Months

  11. Number of patients with procedural success

    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).

    Measured: 2 months

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

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

    Measured: 2 months

  13. Changes in functional status based on Modified Rankin Scale

    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).

    Measured: 24 months

  14. Changes in Quality of life

    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.

    Measured: 12 months

  15. Compliance to NOAC

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

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

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

    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

    Measured: 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Aug 2018
  2. Study start1 Jan 2019
  3. Primary completion1 Jan 2026 (estimated)
  4. Study completion1 Oct 2030 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
Single blind
Who is masked
Outcomes assessor
Enrolment
750 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03642509
Sponsor's protocol ID
Occlusion-AF-AUH250418-32
Acronym
Occlusion-AF
Status last verified
Dec 2023
First submitted
6 Jul 2018
Last updated
21 Dec 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • Zoni-Berisso M, Lercari F, Carazza T, Domenicucci S. Epidemiology of atrial fibrillation: European perspective. Clin Epidemiol. 2014 Jun 16;6:213-20. doi: 10.2147/CLEP.S47385. eCollection 2014.

    PubMed 24966695

  • Marini C, De Santis F, Sacco S, Russo T, Olivieri L, Totaro R, Carolei A. Contribution of atrial fibrillation to incidence and outcome of ischemic stroke: results from a population-based study. Stroke. 2005 Jun;36(6):1115-9. doi: 10.1161/01.STR.0000166053.83476.4a. Epub 2005 May 5.

    PubMed 15879330

  • Blackshear JL, Odell JA. Appendage obliteration to reduce stroke in cardiac surgical patients with atrial fibrillation. Ann Thorac Surg. 1996 Feb;61(2):755-9. doi: 10.1016/0003-4975(95)00887-X.

    PubMed 8572814

  • Kirchhof P, Benussi S, Kotecha D, Ahlsson A, Atar D, Casadei B, Castella M, Diener HC, Heidbuchel H, Hendriks J, Hindricks G, Manolis AS, Oldgren J, Popescu BA, Schotten U, Van Putte B, Vardas P; ESC Scientific Document Group. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J. 2016 Oct 7;37(38):2893-2962. doi: 10.1093/eurheartj/ehw210. Epub 2016 Aug 27. No abstract available.

    PubMed 27567408

  • Connolly SJ, Ezekowitz MD, Yusuf S, Eikelboom J, Oldgren J, Parekh A, Pogue J, Reilly PA, Themeles E, Varrone J, Wang S, Alings M, Xavier D, Zhu J, Diaz R, Lewis BS, Darius H, Diener HC, Joyner CD, Wallentin L; RE-LY Steering Committee and Investigators. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009 Sep 17;361(12):1139-51. doi: 10.1056/NEJMoa0905561. Epub 2009 Aug 30.

    PubMed 19717844

  • Granger CB, Alexander JH, McMurray JJ, Lopes RD, Hylek EM, Hanna M, Al-Khalidi HR, Ansell J, Atar D, Avezum A, Bahit MC, Diaz R, Easton JD, Ezekowitz JA, Flaker G, Garcia D, Geraldes M, Gersh BJ, Golitsyn S, Goto S, Hermosillo AG, Hohnloser SH, Horowitz J, Mohan P, Jansky P, Lewis BS, Lopez-Sendon JL, Pais P, Parkhomenko A, Verheugt FW, Zhu J, Wallentin L; ARISTOTLE Committees and Investigators. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011 Sep 15;365(11):981-92. doi: 10.1056/NEJMoa1107039. Epub 2011 Aug 27.

    PubMed 21870978

  • Giugliano RP, Ruff CT, Braunwald E, Murphy SA, Wiviott SD, Halperin JL, Waldo AL, Ezekowitz MD, Weitz JI, Spinar J, Ruzyllo W, Ruda M, Koretsune Y, Betcher J, Shi M, Grip LT, Patel SP, Patel I, Hanyok JJ, Mercuri M, Antman EM; ENGAGE AF-TIMI 48 Investigators. Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2013 Nov 28;369(22):2093-104. doi: 10.1056/NEJMoa1310907. Epub 2013 Nov 19.

    PubMed 24251359

  • Patel MR, Mahaffey KW, Garg J, Pan G, Singer DE, Hacke W, Breithardt G, Halperin JL, Hankey GJ, Piccini JP, Becker RC, Nessel CC, Paolini JF, Berkowitz SD, Fox KA, Califf RM; ROCKET AF Investigators. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011 Sep 8;365(10):883-91. doi: 10.1056/NEJMoa1009638. Epub 2011 Aug 10.

    PubMed 21830957

  • Diener HC, Connolly SJ, Ezekowitz MD, Wallentin L, Reilly PA, Yang S, Xavier D, Di Pasquale G, Yusuf S; RE-LY study group. Dabigatran compared with warfarin in patients with atrial fibrillation and previous transient ischaemic attack or stroke: a subgroup analysis of the RE-LY trial. Lancet Neurol. 2010 Dec;9(12):1157-1163. doi: 10.1016/S1474-4422(10)70274-X. Epub 2010 Nov 6.

    PubMed 21059484

  • Hankey GJ, Patel MR, Stevens SR, Becker RC, Breithardt G, Carolei A, Diener HC, Donnan GA, Halperin JL, Mahaffey KW, Mas JL, Massaro A, Norrving B, Nessel CC, Paolini JF, Roine RO, Singer DE, Wong L, Califf RM, Fox KA, Hacke W; ROCKET AF Steering Committee Investigators. Rivaroxaban compared with warfarin in patients with atrial fibrillation and previous stroke or transient ischaemic attack: a subgroup analysis of ROCKET AF. Lancet Neurol. 2012 Apr;11(4):315-22. doi: 10.1016/S1474-4422(12)70042-X. Epub 2012 Mar 7.

    PubMed 22402056

  • Easton JD, Lopes RD, Bahit MC, Wojdyla DM, Granger CB, Wallentin L, Alings M, Goto S, Lewis BS, Rosenqvist M, Hanna M, Mohan P, Alexander JH, Diener HC; ARISTOTLE Committees and Investigators. Apixaban compared with warfarin in patients with atrial fibrillation and previous stroke or transient ischaemic attack: a subgroup analysis of the ARISTOTLE trial. Lancet Neurol. 2012 Jun;11(6):503-11. doi: 10.1016/S1474-4422(12)70092-3. Epub 2012 May 8.

    PubMed 22572202

  • Rost NS, Giugliano RP, Ruff CT, Murphy SA, Crompton AE, Norden AD, Silverman S, Singhal AB, Nicolau JC, SomaRaju B, Mercuri MF, Antman EM, Braunwald E; ENGAGE AF-TIMI 48 Investigators. Outcomes With Edoxaban Versus Warfarin in Patients With Previous Cerebrovascular Events: Findings From ENGAGE AF-TIMI 48 (Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48). Stroke. 2016 Aug;47(8):2075-82. doi: 10.1161/STROKEAHA.116.013540. Epub 2016 Jul 7.

    PubMed 27387994

  • Gadsboll K, Staerk L, Fosbol EL, Sindet-Pedersen C, Gundlund A, Lip GYH, Gislason GH, Olesen JB. Increased use of oral anticoagulants in patients with atrial fibrillation: temporal trends from 2005 to 2015 in Denmark. Eur Heart J. 2017 Mar 21;38(12):899-906. doi: 10.1093/eurheartj/ehw658.

    PubMed 28110293

  • Hellfritzsch M, Husted SE, Grove EL, Rasmussen L, Poulsen BK, Johnsen SP, Hallas J, Pottegard A. Treatment Changes among Users of Non-Vitamin K Antagonist Oral Anticoagulants in Atrial Fibrillation. Basic Clin Pharmacol Toxicol. 2017 Feb;120(2):187-194. doi: 10.1111/bcpt.12664. Epub 2016 Oct 28.

    PubMed 27580086

  • Reddy VY, Sievert H, Halperin J, Doshi SK, Buchbinder M, Neuzil P, Huber K, Whisenant B, Kar S, Swarup V, Gordon N, Holmes D; PROTECT AF Steering Committee and Investigators. Percutaneous left atrial appendage closure vs warfarin for atrial fibrillation: a randomized clinical trial. JAMA. 2014 Nov 19;312(19):1988-98. doi: 10.1001/jama.2014.15192.

    PubMed 25399274

Questions about this trial

What is this clinical trial studying?

A study testing Left atrial appendage occlusion and NOAC in people with Atrial Fibrillation and Stroke, run by University of Aarhus at 15 sites in 5 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 21 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 15 sites in Denmark, Finland, Norway, Sweden, Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Kasper Korsholm, MD (004578452254, kasperkorsholm@clin.au.dk), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Composite endpoint of stroke (ischemic and hemorrhagic), systemic embolism, major bleeding and all-cause mortality. (time frame: Up to 5-years from randomization). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03642509, which also lists 22 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Dec 2023.

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