Atrial FibrillationCOMPARE-LAAONCT04676880
Left Atrial Appendage Occlusion for AF Patients Unable to Use Oral Anticoagulation Therapy
A study testing Left atrial appendage occlusion (Watchman FLX or Amplatzer Amulet) in people with Atrial Fibrillation and Anticoagulants and Bleeding Disorders, run by R&D Cardiologie at 14 sites in Netherlands.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Atrial Fibrillation, Anticoagulants and Bleeding Disorders
- What is being tested?
- Left atrial appendage occlusion (Watchman FLX or Amplatzer Amulet)
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 609 participants
- Where
- 14 sitesNetherlands
- Study dates
- 1 Jan 2021to 1 Nov 2026
- 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
- 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.
Who cannot join
- 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
Show all 18Show fewer
- 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
- Stroke within the 3 months prior to inclusion, if not yet clinically stable, and/or without adequate diagnostic or prognostic evaluation, and/or in need of other interventions NL75209.100.20 COMPARE-LAAO Study protocol version 1.4 September 2020
- Planned CEA for significant carotid artery disease
- Major bleeding (BARC criteria>type 2) within 1 month prior to inclusion or longer if it has not been resolved yet
- 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
- Life expectancy of less than 1 year
Trial locations and contacts
14 sites in 1 country.
14 sites in 1 country
Netherlands14 sites
OLVG
Amsterdam, North Holland, 1091 AC
Amsterdam UMC
Amsterdam, North Holland, 1105 AZ
Amphia Hospital
Breda, North Brabant, 4818 CK
Medical Spectrum Twente
Enschede, Overijssel, 7512 KZ
UMC Groningen
Groningen, 9713 GZ
Medical Center Leeuwarden
Leeuwarden, Provincie Friesland, 8934 AD
Leiden UMC
Leiden, South Holland, 2333 ZA
Maastricht UMC
Maastricht, Limburg, 6229 HX
St Antonius Hospital
Nieuwegein, North Holland, 3435 CM
Radboud UMC
Nijmegen, Gelderland, 6525 GA
Erasmus MC
Rotterdam, South Holland, 3015 GD
Haga Hospital
The Hague, South Holland, 2545 AA
UMC Utrecht
Utrecht, 3584 CX
Isala Clinics
Zwolle, Overijssel, 8025 BT
About this study
Official title: Comparing Effectiveness and Safety of Left Atrial Appendage Occlusion for Non-valvular Atrial Fibrillation Patients at High Stroke Risk Unable to Use Oral Anticoagulation Therapy
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.
Read the detailed description
Stroke risk for non-valvular AF is estimated with the CHA2DS2-VASc score. When patients have no risk factors, no anticoagulation is recommended with a Class III, loe B. With 1 risk factor in men and 2 in women, anticoagulation should be considered (class IIA, loe-B). When the CHA2DS2-VASc score is 2 or greater in men (3 or greater in women) anticoagulation is recommended in all with a Class I, loe-A, preferably with a NOAC (class I, loe-A). Platelet inhibitor monotherapy is prohibited with a Class III, loe-A. Patients that have or develop a long-term contra-indication for oral anticoagulation have no class I guideline accepted alternative. Instead it is recommended to modify conditions or interrupt anticoagulants (Class IIB, loe-B). Resumption of oral anticoagulants should be guided by a multidisciplinary team that weighs the risks and benefits of such a course of action (class IIA, loe-C). In patients after an intracranial haemorrhage (ICH), it is recommended to initiate or resume anticoagulation after 2-4 weeks (class IIA, loeC) choosing an agent with low intracranial bleeding risk.
There is insufficient data to support the choice of anticoagulant and no evidence at all for avoiding stroke prevention altogether, which has led to wide variations in restarting oral anticoagulation often after several months of abstinence. Over 60% does not even resume therapy after anticoagulation-associated ICH.
As the LAA is the dominant source for cardioembolic stroke, mechanical percutaneous endocardial occlusion procedures have been developed. The WATCHMAN and AMULET (both FDA- and CE approval) are the most used but others are emerging. Basically, a cardiac catheterization is performed from the Femoral Vein, passing a 14F catheter through the Inferior Caval Vein and the interatrial septum to the left atrium. The delivery system is then positioned in the LAA ostium, and the device is deployed blocking the entrance and eliminating the LAA from the circulation. The implant procedure is usually guided by trans-esophageal echo imaging to assess device size and determine optimal position before it can be released. Adequate closure is achieved in 99% of patients nowadays, with a low and manageable procedural risk of 2.5%. To avoid device-related thrombus during reendothelialization patients are treated with dual antithrombotic agents, aspirin and clopidogrel in the first 3 months, which is narrowed down to aspirin until 1 year after which time it may be discontinued.
The 5-year follow up of PROTECT-AF and PREVAIL showed that LAAO was non-inferior to vitamin K antagonist (VKA) for the primary endpoint of stroke/ TIA/systemic embolism/death (HR 0.82, p-value 0.3), while VKA-patients had significantly more major bleeding events after the implant (HR 0.48, p=0.0003). WATCHMAN LAAO is CE and FDA approved and worldwide almost 100.000 WATCHMAN implantations have now been performed. Currently no RCT outcome data are available comparing WATCHMAN LAAO to any type of NOAC. For AMULET and other LAAO devices there are no published RCT compared to either VKA or NOAC. The EWOLUTION all-comers registry data in over 1000 AF pts (73% unable to use (N)OAC, CHA2DS2-VASc 4.7) WATCHMAN LAAO showed stroke and bleeding rates 80% and 46% lower than expected compared to historical data. In 2 similar AMPLATZER-AMULET LAAO registries of >1000 AF patients, stroke and bleeding rates were 50-60% lower. Both in the 2020 ESC and the 2019 AHA/ACC guidelines, LAAO has received a Class IIb, loe-B recommendation for stroke prevention in patients with AF that have non-reversible contra-indications for long-term anticoagulation.
The COMPARE-LAAO trial studies the effectiveness and safety of LAAO as an alternative means for stroke prevention, to establish whether outcomes in The Netherlands are comparable to literature. In the setting of a randomized controlled trial, LAA will be compared to usual care of anti-platelet therapy or nothing based on individual physician's assessment. Cost-effectiveness will be studied by comparing the additional cost of the procedure to cost of usual care, and the differences in cost between both arms for complications due to stroke and other embolism.
- Being tested
- Left atrial appendage occlusion (Watchman FLX or Amplatzer Amulet)
- Keywords
- Atrial fibrillation, Anticoagulation, Left atrial appendage occlusion, Left atrial appendage, Occluder, Stroke
- Medical subject headings
- Atrial Fibrillation, Hemostatic Disorders, Stroke
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Left atrial appendage occlusion (Watchman FLX or Amplatzer Amulet)Device
Also called Watchman FLX device, 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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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). |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to first occurrence of ischemic or hemorrhagic or undetermined stroke.
Measured: 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.
Measured: 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
Measured: Procedure up to 30 days
Secondary outcomes (19)
The composite event rate of stroke (ischemic or hemorrhagic), TIA, systemic embolism and cardiovascular death.
Measured: Through study completion, an average of 3 years
Ischemic stroke event rate
Measured: Through study completion, an average of 3 years
Disabling stroke event rate
Measured: Through study completion, an average of 3 years
Hemorrhagic stroke event rate
Measured: Through study completion, an average of 3 years
TIA event rate
Measured: Through study completion, an average of 3 years
Systemic embolism (SE) event rate
Measured: Through study completion, an average of 3 years
Mortality (cardiovascular) event rate
Measured: Through study completion, an average of 3 years
Mortality (all-cause) event rate
Measured: Through study completion, an average of 3 years
Major bleeding event rate (according to BARC criteria)
Measured: both procedural up to 7 days, as well as total (through study completion, an average of 3 years)
Minor bleeding event rate
Measured: both procedural up to 7 days, as well as total (through study completion, an average of 3 years)
Number of patients with successful device deployment
Measured: procedural up to 7 days
Adverse events rate
Measured: at 30 days, and from 30 days until end of follow up (max. 5 years, avarage of 3 years)
Device related thrombus event rate
Measured: Through study completion, an average of 3 years
Net-clinical benefit of efficacy and safety endpoint (calculated as the difference in time to first occurence of stroke, TIA and SE in both arms in comparison to the 30-day rate of procedural complications in both groups)
Measured: Through study completion, an average of 3 years
Patient-reported health quality assessed by the SF12 questionnaire
SF-12 stands for 12-Item Short Form Health Survey. Every question is scored from 1 to 5 points. Higher scores indicate better outcomes.
Measured: baseline, 3, 6, 12 months, after that on a yearly base (until the end of the study, max follow up +/- 5 years)
Anxiety and depression assessed by the HADS questionnaire
HADS questionnaire stands for Hospital Anxiety and Depression Scale. The scale of the HADS-questionnaire lies between 0-21.
For both anxiety and depression, de scores indicate:
- 0-7 = normal
- 8-10 = borderline normal
- 11-21 = abnormal
Measured: baseline, 3, 6, 12 months, after that on a yearly base (until the end of the study, max follow up +/- 5 years)
Generic health status assessed by the EQ5D5L questionnaire (in order to perform a cost-effectiveness analysis)
EQ5D5L is a standardized instrument for measuring generic health status, widely used for (among other things) economic evaluations.
The EQ5D5L consists of 5 dimensions (mobility, self care, usual activities, pain/discomfort, anxiety/depression), each with a scale/digit of 1-5 (where 1 indicates no problem and 5 indicates extreme problems).
The digits for 5 dimensions can be combined in a 5-digit number describing a patients health state (this is no cardinal score).
From these 5-digits numbers, a index value can be calculated. These index values will be compared between the different time frames and groups.
Measured: Through study completion, an average of 3 years. Questionnaires will be send on a half yearly basis.
Medical consumption (in order to perform a cost-effectiveness analysis)
iMCQ stands for iMTA Medical Consumption Questionnaire and is developed in order to improve standardization in measurement in health economic evaluation.
The iMCQ is a generic instrument for measuring medical costs. The iMCQ includes questions related to frequently occurring contacts with health care providers.
Measured: Through study completion, an average of 3 years. Questionnaires will be send on a half yearly basis.
Productivity losses (in order to perform a cost-effectiveness analysis)
iPCQ stands for iMTA Productivity Cost Questionnaire and is developed in order to improve standardization in measurement in health economic evaluation.
The iPCQ is a generic questionnaire for the measurement of productivity losses.
Measured: Through study completion, an average of 3 years. Questionnaires will be send on a half yearly basis.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Dec 2020
- Study start1 Jan 2021
- Primary completion1 May 2026 (estimated)
- Study completion1 Nov 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Atrial FibrillationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 609 participants (estimated)
Sponsor and investigators
- Lead sponsor
- R&D Cardiologie
- Sponsor type
- University, hospital or other
- Collaborators
- ZonMw: The Netherlands Organisation for Health Research and Development
- Responsible party
- Principal investigator, L.V.A. Boersma, R&D Cardiologie
- Investigators
- Lucas VA Boersma, Prof. Dr., Principal investigator, St Antonius Ziekenhuis Nieuwegein
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04676880
- Sponsor's protocol ID
- RDC-2020.01
- Acronym
- COMPARE-LAAO
- Status last verified
- Jun 2024
- First submitted
- 25 Nov 2020
- Last updated
- 21 Jun 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- Yes: During/at the end of the study, the database will be transfered to the 'Dutch Heart Registry' (https://nederlandsehartregistratie.nl/). This registry keeps track of all implantable devices that are within the national health insurance package. In this way, data can be obtained by other researchers (fair data principle).
Publications
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.
PubMed 35537503
Study at a glance
From the registry record, last updated by the sponsor on 21 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparing Effectiveness and Safety of Left Atrial Appendage Occlusion for Non-valvular Atrial Fibrillation Patients at High Stroke Risk Unable to Use Oral Anticoagulation Therapy
- ClinicalTrials.gov ID
- NCT04676880
- Acronym / sponsor ID
- COMPARE-LAAO / RDC-2020.01
- Keywords
- Atrial fibrillation, Anticoagulation, Left atrial appendage occlusion, Left atrial appendage, Occluder, Stroke
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 609 participants (estimated)
- Lead sponsor
- R&D CardiologieUniversity, hospital or other
- Collaborators
- ZonMw: The Netherlands Organisation for Health Research and Development
- Study start
- 1 Jan 2021 (actual)
- Primary completion
- 1 May 2026 (estimated)
- Study completion
- 1 Nov 2026 (estimated)
- First posted
- 21 Dec 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Stroke risk for non-valvular AF is estimated with the CHA2DS2-VASc score. When patients have no risk factors, no anticoagulation is recommended with a Class III, loe B. With 1 risk factor in men and 2 in women, anticoagulation should be considered (class IIA, loe-B). When the CHA2DS2-VASc score is 2 or greater in men (3 or greater in women) anticoagulation is recommended in all with a Class I, loe-A, preferably with a NOAC (class I, loe-A). Platelet inhibitor monotherapy is prohibited with a Class III, loe-A. Patients that have or develop a long-term contra-indication for oral anticoagulation have no class I guideline accepted alternative. Instead it is recommended to modify conditions or interrupt anticoagulants (Class IIB, loe-B). Resumption of oral anticoagulants should be guided by a multidisciplinary team that weighs the risks and benefits of such a course of action (class IIA, loe-C). In patients after an intracranial haemorrhage (ICH), it is recommended to initiate or resume anticoagulation after 2-4 weeks (class IIA, loeC) choosing an agent with low intracranial bleeding risk.
There is insufficient data to support the choice of anticoagulant and no evidence at all for avoiding stroke prevention altogether, which has led to wide variations in restarting oral anticoagulation often after several months of abstinence. Over 60% does not even resume therapy after anticoagulation-associated ICH.
As the LAA is the dominant source for cardioembolic stroke, mechanical percutaneous endocardial occlusion procedures have been developed. The WATCHMAN and AMULET (both FDA- and CE approval) are the most used but others are emerging. Basically, a cardiac catheterization is performed from the Femoral Vein, passing a 14F catheter through the Inferior Caval Vein and the interatrial septum to the left atrium. The delivery system is then positioned in the LAA ostium, and the device is deployed blocking the entrance and eliminating the LAA from the circulation. The implant procedure is usually guided by trans-esophageal echo imaging to assess device size and determine optimal position before it can be released. Adequate closure is achieved in 99% of patients nowadays, with a low and manageable procedural risk of 2.5%. To avoid device-related thrombus during reendothelialization patients are treated with dual antithrombotic agents, aspirin and clopidogrel in the first 3 months, which is narrowed down to aspirin until 1 year after which time it may be discontinued.
The 5-year follow up of PROTECT-AF and PREVAIL showed that LAAO was non-inferior to vitamin K antagonist (VKA) for the primary endpoint of stroke/ TIA/systemic embolism/death (HR 0.82, p-value 0.3), while VKA-patients had significantly more major bleeding events after the implant (HR 0.48, p=0.0003). WATCHMAN LAAO is CE and FDA approved and worldwide almost 100.000 WATCHMAN implantations have now been performed. Currently no RCT outcome data are available comparing WATCHMAN LAAO to any type of NOAC. For AMULET and other LAAO devices there are no published RCT compared to either VKA or NOAC. The EWOLUTION all-comers registry data in over 1000 AF pts (73% unable to use (N)OAC, CHA2DS2-VASc 4.7) WATCHMAN LAAO showed stroke and bleeding rates 80% and 46% lower than expected compared to historical data. In 2 similar AMPLATZER-AMULET LAAO registries of >1000 AF patients, stroke and bleeding rates were 50-60% lower. Both in the 2020 ESC and the 2019 AHA/ACC guidelines, LAAO has received a Class IIb, loe-B recommendation for stroke prevention in patients with AF that have non-reversible contra-indications for long-term anticoagulation.
The COMPARE-LAAO trial studies the effectiveness and safety of LAAO as an alternative means for stroke prevention, to establish whether outcomes in The Netherlands are comparable to literature. In the setting of a randomized controlled trial, LAA will be compared to usual care of anti-platelet therapy or nothing based on individual physician's assessment. Cost-effectiveness will be studied by comparing the additional cost of the procedure to cost of usual care, and the differences in cost between both arms for complications due to stroke and other embolism.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Intervention arm - Left atrial appendage occlusion (with Watchman FLX or Amplatzer Amulet device) | Experimental | Device: Left atrial appendage occlusion (Watchman FLX or Amplatzer Amulet)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. |
| 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). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (18 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Left atrial appendage occlusion (Watchman FLX or Amplatzer Amulet)Also: Watchman FLX device, Amplatzer Amulet deviceCurrently, 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. | Device | Intervention arm - Left atrial appendage occlusion (with Watchman FLX or Amplatzer Amulet device) |
Primary outcome
Time to first occurrence of ischemic or hemorrhagic or undetermined stroke.
Time frame: 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.
Time frame: Minimal follow up is 1 year, maximum follow up +/- 5 years
Incidence of procedural complications
Time frame: Procedure up to 30 days
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
19 secondary outcomes
The composite event rate of stroke (ischemic or hemorrhagic), TIA, systemic embolism and cardiovascular death.
Time frame: Through study completion, an average of 3 years
Ischemic stroke event rate
Time frame: Through study completion, an average of 3 years
Disabling stroke event rate
Time frame: Through study completion, an average of 3 years
Hemorrhagic stroke event rate
Time frame: Through study completion, an average of 3 years
TIA event rate
Time frame: Through study completion, an average of 3 years
Systemic embolism (SE) event rate
Time frame: Through study completion, an average of 3 years
Mortality (cardiovascular) event rate
Time frame: Through study completion, an average of 3 years
Mortality (all-cause) event rate
Time frame: Through study completion, an average of 3 years
Major bleeding event rate (according to BARC criteria)
Time frame: both procedural up to 7 days, as well as total (through study completion, an average of 3 years)
Minor bleeding event rate
Time frame: both procedural up to 7 days, as well as total (through study completion, an average of 3 years)
Number of patients with successful device deployment
Time frame: procedural up to 7 days
Adverse events rate
Time frame: at 30 days, and from 30 days until end of follow up (max. 5 years, avarage of 3 years)
Device related thrombus event rate
Time frame: Through study completion, an average of 3 years
Net-clinical benefit of efficacy and safety endpoint (calculated as the difference in time to first occurence of stroke, TIA and SE in both arms in comparison to the 30-day rate of procedural complications in both groups)
Time frame: Through study completion, an average of 3 years
Patient-reported health quality assessed by the SF12 questionnaire
Time frame: baseline, 3, 6, 12 months, after that on a yearly base (until the end of the study, max follow up +/- 5 years)
Anxiety and depression assessed by the HADS questionnaire
Time frame: baseline, 3, 6, 12 months, after that on a yearly base (until the end of the study, max follow up +/- 5 years)
Generic health status assessed by the EQ5D5L questionnaire (in order to perform a cost-effectiveness analysis)
Time frame: Through study completion, an average of 3 years. Questionnaires will be send on a half yearly basis.
Medical consumption (in order to perform a cost-effectiveness analysis)
Time frame: Through study completion, an average of 3 years. Questionnaires will be send on a half yearly basis.
Productivity losses (in order to perform a cost-effectiveness analysis)
Time frame: Through study completion, an average of 3 years. Questionnaires will be send on a half yearly basis.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Jun 2024.
- Derived from this study: PubMed 35537503Huijboom 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.
- Individual participant dataSharing planned: Yes. During/at the end of the study, the database will be transfered to the 'Dutch Heart Registry' (https://nederlandsehartregistratie.nl/). This registry keeps track of all implantable devices that are within the national health insurance package. In this way, data can be obtained by other researchers (fair data principle).
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lucas VA Boersma, Prof. Dr. principal investigator
St Antonius Ziekenhuis Nieuwegein
14 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Left atrial appendage occlusion (Watchman FLX or Amplatzer Amulet) in people with Atrial Fibrillation and Anticoagulants and Bleeding Disorders, run by R&D Cardiologie at 14 sites in Netherlands.
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 6 inclusion and 18 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: under way, not looking for participants, as of the sponsor's last update on 21 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 14 sites in Netherlands. 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?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time to first occurrence of ischemic or hemorrhagic or undetermined stroke. (time frame: Minimal follow up is 1 year, maximum follow up +/- 5 years). The study lists 3 primary outcomes in all. 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 NCT04676880, which also lists 1 linked publication.
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 Jun 2024; AzTrials last refreshed its copy on 6 Nov 2026.