Left Atrial Appendage Occlusion for AF Patients Unable to Use Oral Anticoagulation Therapy

NCT04676880 | Active Not Recruiting DMC FDA Device

• 1 other identifier: RDC-2020.01
• Study Type: interventional
• Target: 609
• Locations: 1 country
• Sites: 14

Brief Summary

Up to 5% of Atrial Fibrillation (AF) patients may have or develop contraindications to use oral anticoagulation (OAC). Randomized controlled trial (RCT) data suggest that Left Atrial Appendage Occlusion (LAAO) may provide a non-inferior alternative for cardioembolic stroke protection in patients tolerant to OAC. However, RCT data for LAAO is lacking in patients with contra-indications to OAC using antiplatelet (APT) or no therapy as usual care. The hypothesis underlying this trial is to demonstrate that LAAO is superior to usual care for the prevention of stroke.

Conditions

Atrial Fibrillation; Anticoagulants and Bleeding Disorders

Keywords

Atrial fibrillation; Anticoagulation; Left atrial appendage occlusion; Left atrial appendage; Occluder; Stroke

Outcome Measures

Primary Outcomes (3)

• Time to first occurrence of ischemic or hemorrhagic or undetermined stroke.

  Minimal follow up is 1 year, maximum follow up +/- 5 years

• Time to first occurrence of the composite of stroke (ischemic or hemorrhagic or undetermined), TIA and systemic embolism.

  Minimal follow up is 1 year, maximum follow up +/- 5 years

• Incidence of procedural complications

  Defined as major procedure-related events that require prolonged hospitalization and/or specific treatment, or that lead to permanent physical or mental disability, including but not limited to: pericardiocentesis, major access site bleeding (BARC), any other major bleeding (BARC), device dislocation from the LAA to the heart or aorta, stroke, death, or other severe complications that are considered due to the procedure

  Procedure up to 30 days

Secondary Outcomes (19)

• The composite event rate of stroke (ischemic or hemorrhagic), TIA, systemic embolism and cardiovascular death.

  Through study completion, an average of 3 years

• Ischemic stroke event rate

  Through study completion, an average of 3 years

• Disabling stroke event rate

  Through study completion, an average of 3 years

• Hemorrhagic stroke event rate

  Through study completion, an average of 3 years

• TIA event rate

  Through study completion, an average of 3 years

Study Arms (2)

Intervention arm - Left atrial appendage occlusion (with Watchman FLX or Amplatzer Amulet device)

EXPERIMENTAL

Patients randomized to the intervention arm will receive left atrial appendage occlusion. In order to prevent device-related thrombus, they will use dual antiplatelet therapy (acetylsalicylzuur + clopidogrel) for three months and single antiplatelet therapy (acetylsalicylzuur) until at least 12 months after the procedure.

Device: Left atrial appendage occlusion (Watchman FLX or Amplatzer Amulet)

Control arm - no or usual care

NO INTERVENTION

The patients in the control arm will stay on optimal treatment as decided by the referring physician (antiplatelet therapy or nothing).

Interventions

Left atrial appendage occlusion (Watchman FLX or Amplatzer Amulet) DEVICE

Currently, there are two devices available on the Dutch market, Watchman and Amulet. After randomization to the intervention arm, additional randomization for type of device will follow. If the amount of procedures is too small to implant two devices, the centre will implant a device of choice.

Also known as: Watchman FLX device, Amplatzer Amulet device

Intervention arm - Left atrial appendage occlusion (with Watchman FLX or Amplatzer Amulet device)

Eligibility Criteria

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

You may qualify if:

• Documented non-valvular AF (paroxysmal or non-paroxysmal) and
• CHA2DS2-VASc score of 2 or more and
• Unsuitable for long-term use of oral anticoagulation as determined by the referring physician team as well as the multidisciplinary team in the study hospital and
• Suitable for dual APT for at least 3 months and single APT from 3 until at most 12 months and
• At least 18 years of age, and willing and able to provide informed consent and adhere to study rules and regulations and follow-up
• The decision of suitability for LAAO should be made by a multidisciplinary team consisting of at least an echocardiographist, an implanting cardiologist, and a cardiac surgeon. The decision of unsuitability for oral anticoagulation by the referring and implanting centers will be clearly and extensively documented in the study charts. This should include the support of physicians other than the referring and implanting cardiologist. These physicians should be specialists in the field where the contra-indication arises such as neurology, gastro-enterology, internal medicine, urology, or other specialties. In many cases the contra-indication may be due to (repeated) major bleeding.Bleeding will be classified according to the BARC criteria as major with a score of 3 or more. The risk of recurrent bleeding should be established by a multidisciplinary team, as well as the decision that the risk of bleeding recurrence outweighs the benefit of restarting oral anticoagulation, which will be documented in the charts. Alternative reasons not to use anticoagulation should be major and irreversible. These may be highly variable and may include but are not limited to occupational or life-style hazards, drug side-effects, ineffectiveness, intolerance, renal or liver failure, falling hazards, vascular problems, cerebral amyloid deposition, and coagulation disorders.

You may not qualify if:

• Any invasive cardiac procedure within 30 days prior to randomization and 90 days after LAAO that would interfere with the study follow-up and medication
• Unsuitable LAA anatomy for closure or thrombus in the LAA at the time of procedure
• Contraindications or unfavourable conditions to perform cardiac catheterization or TEE
• Atrial septal malformations, atrial septal defect or a high-risk patient foramen ovale that may cause thrombo-embolic events
• Atrial septal defect repair or closure device or a patent foramen ovale repair or any other anatomical condition as this may preclude an LAAO procedure
• LVEF\<31% and/or heart failure NYHA 3-4
• Mitral valve regurgitation grade 3 or more
• Mitral stenosis as this makes AF by definition valvular in nature
• Aortic valve stenosis (AVA\<1.0 cm2 or Pmax\>50 mmHg) or regurgitation grade 3 or more
• Planned cardiac surgery for any reason within 3 months
• Planned CEA for significant carotid artery disease
• Compelling medical reason to use VKA or NOAC (e.g. mechanical heart valve, pulmonary embolism, ventricular aneurysm)
• Major contraindications for using aspirin or clopidogrel
• (planned) pregnancy
• Participation in any other clinical trial that interferes with the current study

Sponsors & Collaborators

• R&D Cardiologie: lead
• ZonMw: The Netherlands Organisation for Health Research and Development: collaborator

Study Sites (14)

Radboud UMC

Nijmegen, Gelderland, 6525 GA, Netherlands

Location

Maastricht UMC

Maastricht, Limburg, 6229 HX, Netherlands

Location

Amphia Hospital

Breda, North Brabant, 4818 CK, Netherlands

Location

OLVG

Amsterdam, North Holland, 1091 AC, Netherlands

Location

Amsterdam UMC

Amsterdam, North Holland, 1105 AZ, Netherlands

Location

St Antonius Hospital

Nieuwegein, North Holland, 3435 CM, Netherlands

Location

Medical Spectrum Twente

Enschede, Overijssel, 7512 KZ, Netherlands

Location

Isala Clinics

Zwolle, Overijssel, 8025 BT, Netherlands

Location

Medical Center Leeuwarden

Leeuwarden, Provincie Friesland, 8934 AD, Netherlands

Location

Leiden UMC

Leiden, South Holland, 2333 ZA, Netherlands

Location

Erasmus MC

Rotterdam, South Holland, 3015 GD, Netherlands

Location

Haga Hospital

The Hague, South Holland, 2545 AA, Netherlands

Location

UMC Groningen

Groningen, 9713 GZ, Netherlands

Location

UMC Utrecht

Utrecht, 3584 CX, Netherlands

Location

Related Publications (1)

• Huijboom M, Maarse M, Aarnink E, van Dijk V, Swaans M, van der Heijden J, IJsselmuiden S, Folkeringa R, Blaauw Y, Elvan A, Stevenhagen J, Vlachojannis G, van der Voort P, Westra S, Chaldoupi M, Khan M, de Groot J, van der Kley F, van Mieghem N, van Dijk E, Dijkgraaf M, Tijssen J, Boersma L. COMPARE LAAO: Rationale and design of the randomized controlled trial "COMPARing Effectiveness and safety of Left Atrial Appendage Occlusion to standard of care for atrial fibrillation patients at high stroke risk and ineligible to use oral anticoagulation therapy". Am Heart J. 2022 Aug;250:45-56. doi: 10.1016/j.ahj.2022.05.001. Epub 2022 May 7.

  PMID: 35537503 DERIVED

MeSH Terms

Conditions

Atrial Fibrillation; Hemostatic Disorders; Stroke

Condition Hierarchy (Ancestors)

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

Study Officials

• Lucas VA Boersma, Prof. Dr.

  St Antonius Ziekenhuis Nieuwegein

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical professor

Model Details: This trial is set-up as an open-label, national multicentre, superiority randomized controlled trial where patients will be randomized in a 2:1 fashion to the device arm or the usual care arm.

Study Record Dates

• First Submitted: November 25, 2020
• First Posted: December 21, 2020
• Study Start: January 1, 2021
• Primary Completion: May 1, 2026
• Study Completion (Estimated): November 1, 2026
• Last Updated: June 21, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: After publishing the main study articles, all data will be available.
• Access Criteria: Specific degrees in the field of research have to be demonstrated, as well as links with hospitals or research institutes (e.g. an employee contract) of the researcher/physician.

Locations

NL (14)