Left Atrial Appendage Occlusion vs. NOAC for Atrial Fibrillation

(CATALYST Trial)

Recruiting at 139 trial locations

Overseen By Carey Kimmelstiel, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Abbott Medical Devices

Must be taking: NOACs

Must not be taking: P2Y12 inhibitors

Disqualifiers: Mechanical valve, Severe renal failure, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 3 years

2650 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores two methods to assist people with atrial fibrillation (AF), a heart condition that can lead to strokes. One group will use the Amplatzer Amulet LAA Occluder, a device designed to block a part of the heart where clots may form. The other group will take blood-thinning medication known as NOACs (Non-Vitamin K Oral Anticoagulants). Individuals with non-valvular AF, who are at high risk for stroke and can take NOACs long-term, might be suitable for this trial. As an unphased trial, this study provides a unique opportunity to explore innovative treatments for AF and contribute to advancing medical knowledge.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you must be eligible for long-term NOAC therapy and able to comply with the required medication regimen if you are in the Control Group or after the device implant if you are in the Device Group.

What prior data suggests that the Amulet LAA occluder is safe for patients with atrial fibrillation?

Research has shown that the Amplatzer Amulet LAA Occluder is generally safe for people with non-valvular atrial fibrillation (AF). In one study, over 96% of patients did not need blood thinners for three years after receiving the device. Another study reported a low death rate of 3.9% after 12 months and a low risk of stroke or blood clots at 18 months, with only 2.8% of patients experiencing these issues. These findings suggest that the device is well-tolerated, with few serious side effects.

Non-vitamin K oral anticoagulants (NOACs), already approved to prevent strokes in people with AF, are generally safe but can increase the risk of bleeding due to their blood-thinning effects.

Both treatments are considered safe, but each presents different risks and benefits. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the Amplatzer Amulet LAA Occluder because it offers a mechanical solution to reducing stroke risk in patients with atrial fibrillation, unlike traditional blood thinners like NOACs (Non-Vitamin K Oral Antagonists). This device is implanted to physically block the left atrial appendage, which is a common source of blood clots in atrial fibrillation patients. This approach is particularly appealing for patients who cannot tolerate blood thinners due to bleeding risks. By providing a non-pharmacological option, the Amulet could offer a safer alternative for long-term stroke prevention in these patients.

What evidence suggests that this trial's treatments could be effective for atrial fibrillation?

This trial will compare the Amplatzer Amulet LAA occluder with Non-Vitamin K Oral Antagonists (NOACs) for patients with non-valvular atrial fibrillation (AF) who have a high risk of stroke. Studies have shown that the Amplatzer Amulet LAA occluder is effective. Specifically, research indicates that over 96% of patients using the Amulet device did not need blood-thinning medication for three years. Additionally, the device reduced the risk of ischemic stroke (a type of stroke caused by a blood clot) by 67% compared to expectations. The Amulet device also closed off the left atrial appendage (a small pouch in the heart) more effectively than earlier devices. These findings suggest that the Amulet occluder might be a strong alternative to NOACs, which are commonly used blood-thinning pills. ^{1 2 5 6 7}

Who Is on the Research Team?

Vivek Reddy, MD

Principal Investigator

Mt. Sinai Medical Center

Are You a Good Fit for This Trial?

This trial is for adults with non-valvular atrial fibrillation at high risk of stroke (CHA2DS2-VASc score ≥ 3) who can take long-term NOAC therapy. Participants must be able to follow the medication regimen, attend follow-up visits, and provide informed consent. Exclusions include mechanical heart valves, active infections, recent strokes or surgeries, severe renal failure, life expectancy under 2 years, and certain allergies.

Inclusion Criteria

I am at high risk for stroke, with a CHA2DS2-VASc score of 3 or more.

Able to understand, and is willing to provide, written informed consent to participate in the trial, prior to any clinical investigation related procedure or assessment

Able to comply with the required medication regimen post-device implant if subject is randomized to the Device Group or subject is a Roll-in

Exclusion Criteria

I have had blood clots in my veins without a known cause, more than once.

You are allergic to any part of the Amulet LAA occluder device, like nickel.

My atrial fibrillation is caused by a temporary condition.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomized to receive either the Amplatzer Amulet LAA occluder or a NOAC medication

3 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

What Are the Treatments Tested in This Trial?

Interventions

• Amplatzer Amulet LAA Occluder
• Non-Vitamin K Oral Antagonists

Trial Overview The study compares the Amulet LAA occlusion device's safety and effectiveness against Non-Vitamin K Oral Antagonists (NOACs) in preventing stroke in patients with atrial fibrillation. It's a randomized control trial where participants are equally divided into two groups: one receiving the Amulet device and the other NOACs chosen by physicians.

How Is the Trial Designed?

Group I: Device Group Experimental Treatment 1 Intervention

Randomized to Amplatzer Amulet LAA occluder

Group II: Control Group Active Control 1 Intervention

Randomized to NOAC

Amplatzer Amulet LAA Occluder is already approved in United States, European Union for the following indications:

Approved in United States as Amplatzer Amulet LAA Occluder for:

• Reduction of stroke risk in patients with non-valvular atrial fibrillation

Approved in European Union as Amplatzer Amulet LAA Occluder for:

• Prevention of thromboembolic complications associated with non-valvular atrial fibrillation

Who Is Running the Clinical Trial?

Abbott Medical Devices

Lead Sponsor

Trials

659

Recruited

420,000+

Founded

1888

Headquarters

Abbott Park, Illinois, USA

Known For

Medical Devices Innovation

Top Products

FreeStyle Libre, MitraClip, XIENCE Stents, TECNIS IOLs

Dr. Etahn Korngold

Abbott Medical Devices

Chief Medical Officer

Medical training at Harvard Medical School and Massachusetts General Hospital

Robert B. Ford

Abbott Medical Devices

Chief Executive Officer since 2020

Bachelor's degree from Boston College, MBA from UC Berkeley, Haas School of Business

Published Research Related to This Trial

A meta-analysis of seven studies involving 2926 patients found that left atrial appendage occlusion (LAAO) using either the Amplatzer Amulet or Watchman 2.5 devices is a safe procedure with minimal adverse event rates.

There were no significant differences in safety or efficacy outcomes between the two devices, indicating that both are effective options for reducing stroke risk in patients with nonvalvular atrial fibrillation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of the Amplatzer Amulet and Watchman 2.5 for left atrial appendage occlusion: A systematic review and meta-analysis. Zhu, MZ., Song, H., Song, GM., et al.[2022]

In a study of 59 patients undergoing left atrial appendage occlusion (LAAO), the Amplatzer Amulet device demonstrated a significant reduction in residual leaks compared to the Amplatzer Cardiac Plug (ACP), with only 8% of Amulet patients experiencing leaks versus 48% of ACP patients.

Both devices had similar procedural success rates and short-term outcomes, with no major complications like embolization or stroke, indicating that the Amulet is a safe and effective option for LAAO.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Side-by-Side Comparison of LAA Occlusion Performance With the Amplatzer Cardiac Plug and Amplatzer Amulet. Abualsaud, A., Freixa, X., Tzikas, A., et al.[2019]

In a study of 108,697 patients with atrial fibrillation, those who underwent left atrial appendage (LAA) occlusion had a significantly lower risk of all-cause mortality compared to those on non-vitamin K antagonist oral anticoagulant (NOAC) therapy (1.51% vs. 5.60%).

While LAA occlusion showed a mortality benefit, there were no significant differences in the rates of thrombotic events, ischaemic stroke, or intracranial hemorrhage between the two treatment groups, suggesting that LAA occlusion could be a viable alternative for stroke prevention in atrial fibrillation patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes of left atrial appendage occlusion vs. non-vitamin K antagonist oral anticoagulants in atrial fibrillation. Ding, WY., Rivera-Caravaca, JM., Fazio-Eynullayeva, E., et al.[2022]

In a study of 1088 patients with atrial fibrillation, left atrial appendage occlusion (LAAO) using the Amplatzer Amulet device achieved a 99.1% implant success rate and significantly reduced the ischaemic stroke rate by 67% compared to predicted risks.

The procedure demonstrated a low incidence of major adverse events (4.0% within 7 days), with only 1.6% of patients developing device-related thrombus, indicating a favorable safety profile for the Amulet device.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Left atrial appendage occlusion with the Amplatzer™ Amulet™ device: full results of the prospective global observational study. Hildick-Smith, D., Landmesser, U., Camm, AJ., et al.[2021]

In a study of 30 patients with atrial fibrillation at high risk of stroke, the Amplatzer Amulet device successfully closed the left atrial appendage in 96.7% of cases, demonstrating its efficacy as a treatment alternative to anticoagulation therapy.

The procedure was found to be safe, with no reported complications, and it allows for a shift from anticoagulants to antiplatelet medications like acetylsalicylic acid and clopidogrel post-procedure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retrospective study assessing efficacy and safety of left atrial appendage occlusion. Misikova, S., Haramiova, Z., Juhas, S., et al.[2020]

In a study of 1,000 patients (500 undergoing left atrial appendage closure (LAAC) with AMPLATZER occluders and 500 receiving medical therapy), LAAC demonstrated a significant reduction in the risk of stroke, systemic embolism, and cardiovascular death compared to medical therapy, with a hazard ratio of 0.70.

LAAC was associated with lower rates of all-cause and cardiovascular mortality, indicating a net clinical benefit over medical therapy, while showing similar safety profiles in terms of major procedural adverse events and major bleeding.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Left atrial appendage closure versus medical therapy in patients with atrial fibrillation: the APPLY study. Gloekler, S., Fürholz, M., de Marchi, S., et al.[2020]

In the Amulet IDE trial's roll-in cohort of 201 patients with nonvalvular atrial fibrillation, the Amplatzer™ Amulet™ occluder achieved a high device success rate of 99% and a closure rate of 98.9% at 45 days, indicating its efficacy for left atrial appendage occlusion.

The safety profile showed a slightly higher rate of complications in the roll-in cohort (18.4%) compared to the randomized group (14.5%), but the stroke rate was low at 3.1%, similar to the randomized cohort, suggesting that the Amulet device is a safe alternative to anticoagulants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes of the roll-in cohort of the Amulet IDE trial of left atrial appendage occlusion. Lakkireddy, D., Thaler, D., Ellis, CR., et al.[2022]

The left atrial appendage is a major source of blood clots in patients with non-valvular atrial fibrillation, highlighting its importance in managing stroke risk.

Non-vitamin K oral anticoagulants (NOACs) are effective and safe for preventing embolic complications, and percutaneous left atrial appendage closure (LAAC) is a viable option for patients who cannot use long-term oral anticoagulants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Left atrial appendage closure: Six reasons why I wouldn't choose a percutaneous closure for my appendage. Ferlini, M., Rossini, R.[2018]

In a study of 140 patients with non-valvular atrial fibrillation, the LAmbre LAA occluder system demonstrated a 100% implant success rate, comparable to the Amulet and Watchman devices, indicating its effectiveness as an alternative to anticoagulation.

All three devices (LAmbre, Amulet, and Watchman) showed low rates of major peri-procedural adverse events and maintained good clinical outcomes at six months, suggesting they are safe options for left atrial appendage closure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Left atrial appendage occlusion using LAmbre Amulet and Watchman in atrial fibrillation. Chen, S., Chun, KRJ., Bordignon, S., et al.[2020]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37587599/

3-Year Outcomes From the Amplatzer Amulet Left Atrial ... The Amulet occluder demonstrated continued safety and effectiveness with over 96% free of oral anticoagulation usage through 3 years in a high-risk population.

2. jacc.org jacc.org/doi/10.1016/j.jcin.2023.06.022

3-Year Outcomes From the Amplatzer Amulet Left Atrial ... The Amulet occluder demonstrated continued safety and effectiveness with over 96% free of oral anticoagulation usage through 3 years in a high-risk population.

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0735109724103130

5-Year Results From the AMPLATZER Amulet Left Atrial ... The dual-seal Amulet LAA occluder demonstrated noninferior safety and effectiveness with superior LAA occlusion rates compared with the first-generation ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT02879448

NCT02879448 | AMPLATZER™ Amulet™ LAA Occluder Trial The Amulet™ device will be evaluated for safety and efficacy by demonstrating its performance is non-inferior to the commercially available WATCHMAN® left ...

5. my-connext.com my-connext.com/fileadmin/connext/downloads-content/amplatzer-laa/JACC-Amulet-5_years.pdf

5-Year Results From the AMPLATZER Amulet Left Atrial ... In this study, ischemic stroke was reduced by 67% compared with the predicted rate, whereas most patients (93.4%) were free of OAC, a finding suggesting that ...

6. structuralheart.abbott structuralheart.abbott/products/laa-closure-device/amplatzer-amulet-laa-occluder

Amplatzer Amulet LAA Occluder | Left Atrial Appendage ... The Amplatzer Amulet LAA Occluder offers complete closure of the left atrial appendage (LAA) and immediately eliminates the need for oral anticoagulants.

7. accessdata.fda.gov accessdata.fda.gov/cdrh_docs/pdf20/P200049C.pdf

Amplatzer™ Amulet™ Left Atrial Appendage Occluder The high rate of implant success, a 12-month all-cause mortality rate of 3.9%, along with a low rate of ischemic stroke or systemic embolism at. 18 months (2.8 ...