Left Atrial Appendage Closure vs. Novel Anticoagulation Agents in Atrial Fibrillation

NCT02426944 | Completed Phase 4 DMC

• 1 other identifier: PRAGUE - 17
• Study Type: interventional
• Target: 400
• Locations: 1 country
• Sites: 1

Brief Summary

Atrial fibrillation (AF) is the most common cardiac arrhythmia with a prevalence of 1-2%. Without antithrombotic treatment, the annual risk of a cardioembolic event is 5-6%. The source of a cardioembolic event is a thrombus, which usually forms in the left atrial appendage (LAA). The prevention of cardioembolic events involves treatment with anticoagulant drugs, which were limited to, until recently, vitamin K antagonists (e.g. warfarin). Anticoagulant treatment with warfarin can lead to adverse bleeding events, some of which can be life threatening. Recently, two new options for thrombus prevention have been developed. The first is the novel anticoagulants (NOAC), which were associated with slightly better safety profiles due to a lower frequency of intracranial bleeding in large randomized trials . The second option involves interventional occlusion of the LAA. The aim of this project is to compare the LAA occlusion intervention to NOAC pharmacological treatment in a randomized multicenter study of AF patients at high risk of a cardioembolic event.

Conditions

Atrial Fibrillation

Keywords

atrial fibrillation; cardioembolic event; stroke; left atrial appendage closure; novel anticoagulants

Outcome Measures

Primary Outcomes (1)

• Combined endpoint: stroke OR systemic cardioembolic event OR clinically significant bleeding OR cardiovascular death OR procedure or device-related complications

  The primary endpoint is the combination of stroke, other systemic cardiovascular event, clinically significant ISTH major or non-major bleeding (ISTH major: a decrease in hemoglobin level of 20 g/l or more over a 24-hour period, transfusion of 2 or more units of packed red cells, bleeding at a critical site (intracranial, intraspinal, intraocular, pericardial, intramuscular with compartment syndrome, or retroperitoneal), or fatal bleeding; ISTH non-major: requiring hospitalization or invasive procedure, which doesn´t meet the ISTH major criteria), cardiovascular death or procedure or device-related complications (i.e. a pericardial effusion with a need for drainage, surgical or pericardiocentesis; cardioembolic event during the procedure; significant periprocedural bleeding (such as major vascular bleeding with a need for surgical revision, or blood concentrate transfusion); device embolization, or thrombus of the device with a consequent cardioembolic event).

  From the date of randomization until the date of 6 month follow-up visit of the last enrolled patient

Secondary Outcomes (7)

• Stroke

  From the date of randomization until the date of 6 month follow-up visit of the last enrolled patient

• Systemic cardioembolic event

  From the date of randomization until the date of 6 month follow-up visit of the last enrolled patient

• Clinically significant bleeding (ISTH major)

  From the date of randomization until the date of 6 month follow-up visit of the last enrolled patient

• Cardiovascular death

  From the date of randomization until the date of 6 month follow-up visit of the last enrolled patient

• An procedure or device-related complications

  Within 6 months after the procedure

Study Arms (2)

LAAO group

EXPERIMENTAL

Patients will be treated interventionally by left atrial appendage occlusion (LAAO). LAAO will be done using Amulet or Watchman device.

Device: Left atrial appendage closure

NOAC group

EXPERIMENTAL

Patients will be treated by novel anticoagulants (NOAC).

Drug: NOAC

Interventions

NOAC DRUG

Medical arm, patients will be treated by NOAC.

NOAC group

Left atrial appendage closure DEVICE

The patients will be treated by interventional closure of the left atrial appendage.

LAAO group

Eligibility Criteria

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

You may qualify if:

• history of significant bleeding (i.e. bleeding which required intervention or hospitalization), even in the absence of anticoagulation treatment at the time of the bleeding event, or
• a cardioembolic event, which occurred on anticoagulation, or
• a high risk profile of the patient, defined as a CHA2DS2-VASc score ≥ 3 and a HAS-BLED score ≥ 2

You may not qualify if:

• thrombus in the LA or LAA;
• mechanical valve prosthesis;
• mitral stenosis;
• previous LAA ligation during cardiac surgery;
• life expectancy less than 2 years;
• comorbidities other than AF, which present an indication for anticoagulation;
• patent foramen ovale with atrial septal aneurysm
• mobile plaque in the aorta;
• symptomatic atherosclerosis of the carotid artery;
• pericardial effusion greater than 10 mm;
• clinically significant bleeding within the 30 days prior to the scheduled procedure;
• stroke or other cardioembolic event within the 30 days prior to the scheduled procedure;
• acute coronary syndrome within the 90 days prior to the scheduled procedure,
• gravidity,
• significant valvular disease,

Sponsors & Collaborators

• Charles University, Czech Republic: lead
• Ministry of Health, Czech Republic: collaborator

Study Sites (1)

Cardiocenter, 3rd Medical School, Charles University and University Hospital Kralovske Vinohrady

Prague, 10034, Czechia

Location

Related Publications (23)

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• Osmancik P, Neuzil P, Karel T, Waldauf P, Hozmanova J, Hozman M, Kralovec S, Herman D, Petru J, Sediva L, Fischer J, Stepanek L, Mala I, Whang W, Reddy VY. Pulsed field ablation vs sham ablation to treat atrial fibrillation (the PFA-SHAM trial). Heart Rhythm O2. 2025 Aug 7;6(11):1815-1824. doi: 10.1016/j.hroo.2025.07.103. eCollection 2025 Nov.

  PMID: 41357284 DERIVED

• Osmancik P, Herman D, Neuzil P, Hala P, Taborsky M, Kala P, Poloczek M, Stasek J, Haman L, Branny M, Chovancik J, Cervinka P, Holy J, Kovarnik T, Zemanek D, Havranek S, Vancura V, Peichl P, Tousek P, Lekesova V, Jarkovsky J, Novackova M, Benesova K, Widimsky P, Reddy VY; PRAGUE-17 Trial Investigators. 4-Year Outcomes After Left Atrial Appendage Closure Versus Nonwarfarin Oral Anticoagulation for Atrial Fibrillation. J Am Coll Cardiol. 2022 Jan 4;79(1):1-14. doi: 10.1016/j.jacc.2021.10.023. Epub 2021 Nov 5.

  PMID: 34748929 DERIVED

• Osmancik P, Herman D, Neuzil P, Hala P, Taborsky M, Kala P, Poloczek M, Stasek J, Haman L, Branny M, Chovancik J, Cervinka P, Holy J, Kovarnik T, Zemanek D, Havranek S, Vancura V, Opatrny J, Peichl P, Tousek P, Lekesova V, Jarkovsky J, Novackova M, Benesova K, Widimsky P, Reddy VY; PRAGUE-17 Trial Investigators. Left Atrial Appendage Closure Versus Direct Oral Anticoagulants in High-Risk Patients With Atrial Fibrillation. J Am Coll Cardiol. 2020 Jun 30;75(25):3122-3135. doi: 10.1016/j.jacc.2020.04.067.

  PMID: 32586585 DERIVED

MeSH Terms

Conditions

Atrial Fibrillation; Stroke

Interventions

N(4)-oleylcytosine arabinoside; Left Atrial Appendage Closure

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

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: 3. Faculty of Medicine and University Hospital Kralovske Vinohrady

Study Record Dates

• First Submitted: April 16, 2015
• First Posted: April 27, 2015
• Study Start: October 13, 2015
• Primary Completion: July 20, 2019
• Study Completion: July 20, 2019
• Last Updated: June 11, 2021

Record last verified: 2021-06

Locations

CZ (1)