Lambre Device for Atrial Fibrillation

(CORRAL-AF Trial)

Overseen By Stephen Krafchak, MS

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Brian O'Neill

Must be taking: Oral anticoagulants

Must not be taking: Long-term anticoagulants, DAPT

Disqualifiers: Pregnancy, Rheumatic valve disease, Infection, others

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

Compensation: Varies

Number of Visits: 90

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new device designed for people with atrial fibrillation (irregular heartbeat) who face a higher stroke risk, particularly when pill-based treatments are not ideal. It compares the effectiveness of the LAmbre Plus device, which closes off part of the heart, to standard blood-thinning medications like Warfarin and Apixaban. Suitable candidates have atrial fibrillation and seek alternatives to these blood-thinning medications. The trial aims to demonstrate that the device can safely prevent strokes by stopping harmful clots from forming. As an unphased trial, it offers patients the chance to explore innovative treatment options beyond traditional medications.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it mentions that patients must be suitable for short-term oral anticoagulation therapy, so you might need to continue or adjust your current anticoagulation medication.

What prior data suggests that the LAmbre PlusTM device is safe for patients with atrial fibrillation?

Research has shown that the LAmbre PlusTM device is generally well-tolerated by patients with atrial fibrillation. In a study with 101 patients, the device was successfully placed in 98 cases. Over approximately 12 months of follow-up, about 5 out of 100 patients experienced a new issue, indicating that the device is mostly safe to use.

Another study found that the procedure is usually successful and that the device helps prevent strokes related to atrial fibrillation. While some patients might encounter minor issues, the device is generally considered safe.

For those interested in joining a clinical trial with this device, these findings provide reassurance about its safety based on past experiences. ^{1 2 3 4 5}

Why are researchers excited about this trial?

The LAmbre Plus™ device is unique because it offers a new approach to treating atrial fibrillation by physically closing off the left atrial appendage to prevent blood clots, which is different from the standard oral anticoagulants like Apixaban or Warfarin that work by thinning the blood. Researchers are excited about this device because it targets the source of clot formation directly, potentially reducing the risk of bleeding, a common side effect of traditional blood thinners. Additionally, the LAmbre Plus™ device might provide peace of mind for patients who have difficulties managing their anticoagulation therapy due to lifestyle or dietary restrictions associated with oral medications.

What evidence suggests that the LAmbre PlusTM device is effective for atrial fibrillation?

Research has shown that the LAmbre Plus device works well for individuals with non-valvular atrial fibrillation, an irregular heartbeat not caused by a heart valve issue. This condition increases their risk of stroke. Studies have found that the device effectively closes the left atrial appendage, a small pouch in the heart, helping to prevent blood clots that could lead to strokes. The device boasts a high success rate, with some studies reporting 100% success in correct placement. Early results also suggest that the device is safe and effectively reduces stroke risk in the short term. In this trial, participants in the Device Arm will receive the LAmbre Plus device, while those in the Control Arm will receive market-approved oral anticoagulation (OAC) as a comparator. Overall, the LAmbre Plus device offers a promising alternative to blood thinners for preventing strokes in these patients. ^{2 4 5 6 7}

Who Is on the Research Team?

Brian O'Neill, MD

Principal Investigator

Henry Ford Health System

Are You a Good Fit for This Trial?

This trial is for adults with non-valvular atrial fibrillation at increased risk of stroke, who have a CHADS2 score ≥ 2 or CHA2DS2-VASc score ≥ 3 and are recommended for oral anticoagulation therapy. Candidates should be able to follow the study protocol and provide consent. Exclusions include recent stroke, certain heart conditions, planned surgeries, pregnancy, other clinical trials participation, severe infections or heart failure.

Inclusion Criteria

I have a type of irregular heartbeat not caused by a heart valve issue.

My doctor thinks short-term blood thinners are okay for me, but we're looking for a non-drug option.

The patient (or his or her legally authorized representative) has been informed of the nature of the study, agrees to its provisions, and has been provided written informed consent approved by the appropriate Institutional Review Board (IRB) or Ethics Committee (EC)

Exclusion Criteria

My atrial fibrillation was temporary or caused by a specific condition.

I have not had a stroke, mini-stroke, or heart attack in the last 3 months.

I am not pregnant or nursing and do not plan to become pregnant within a year.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Implantation of the LAmbre PlusTM device in patients with non-valvular atrial fibrillation

1 day

In-hospital procedure

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

In-hospital and at 45 days, 6 months, 12 months, and annually up to 5 years

Imaging Follow-up

CT/Imaging or Transesophageal echocardiographic (TEE) follow-up to assess device placement and closure success

1 year

45 days and 1 year

What Are the Treatments Tested in This Trial?

Interventions

• Apixaban
• Betrixaban
• Dabigatran
• Edoxaban
• LAmbre PlusTM
• LAmbreTM
• Rivaroxaban
• Warfarin

Trial Overview The LAmbre PlusTM device's safety and effectiveness in preventing strokes in patients with irregularly shaped appendages is being tested against standard oral anticoagulants like warfarin and dabigatran. The goal is to find a non-pharmacologic alternative for those suitable for short-term OAC but needing long-term solutions.

How Is the Trial Designed?

Group I: Roll-in Arm Experimental Treatment 1 Intervention

225 roll-in subjects

Group II: Device Arm Experimental Treatment 1 Intervention

The LAmbre PlusTM Left Atrial Appendage Closure System (LAmbre device)

Group III: Control Arm Active Control 1 Intervention

Market approved oral anticoagulation (OAC)

Apixaban is already approved in European Union, United States for the following indications:

Approved in European Union as Eliquis for:

• Deep vein thrombosis
• Pulmonary embolism
• Nonvalvular atrial fibrillation

Approved in United States as Eliquis for:

• Deep vein thrombosis
• Pulmonary embolism
• Nonvalvular atrial fibrillation
• Stroke prevention

Who Is Running the Clinical Trial?

Brian O'Neill

Lead Sponsor

Trials

1

Recruited

2,900+

Brian O'Neill MD

Lead Sponsor

Trials

1

Recruited

2,900+

Lifetech Scientific (Shenzhen) Co., Ltd.

Industry Sponsor

Trials

45

Recruited

8,600+

Published Research Related to This Trial

In the ENSURE-AF study involving 2199 patients, edoxaban demonstrated similar efficacy to enoxaparin-warfarin in preventing serious cardiovascular events after electrical cardioversion for non-valvular atrial fibrillation, with fewer events reported in the edoxaban group (0.5% vs. 0.9% for VKA experienced patients).

The safety profile of edoxaban was comparable to that of enox-warf, with no significant differences in major bleeding rates or clinically relevant nonmajor bleeding, regardless of whether patients were experienced or naïve to vitamin K antagonists.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Edoxaban versus warfarin in vitamin K antagonist experienced and naïve patients from the edoxaban versus warfarin in subjects undergoing cardioversion of atrial fibrillation (ENSURE-AF) randomised trial. Kozieł, M., Al-Saady, N., Hjortshøj, SP., et al.[2021]

In a study involving 14 healthy male subjects, macitentan did not alter the pharmacokinetics or pharmacodynamics of warfarin, indicating that the two medications can be safely used together without requiring dose adjustments.

The study found that plasma concentrations of warfarin remained consistent whether macitentan was administered or not, suggesting no significant drug interactions between these two treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Investigation of the effect of macitentan on the pharmacokinetics and pharmacodynamics of warfarin in healthy male subjects. Sidharta, PN., Dietrich, H., Dingemanse, J.[2021]

Healthcare professionals (HCPs) and patients demonstrated satisfactory knowledge of bleeding risks associated with apixaban, with 96.1% of HCPs recognizing symptoms that require immediate attention and 71.2% of patients identifying abnormal bleeding as a significant side effect.

The study found that a significant majority of HCPs (97.8%) who received the Prescriber Guide utilized it in patient discussions, and 90.9% of patients who received the Patient Alert Card read it at least once, indicating effective distribution and utilization of these educational materials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluating the Effectiveness of Apixaban Additional Risk Minimisation Measures Using Surveys in Europe. Mayall, S., Kahlon, R., Al-Dakkak, I., et al.[2021]

In a study of 21,038 atrial fibrillation patients in Germany, edoxaban was found to be more effective than other oral anticoagulants, showing significantly lower risks of ischemic stroke or systemic embolism compared to apixaban, dabigatran, rivaroxaban, and vitamin K antagonists.

Edoxaban also exhibited a favorable safety profile, with lower risks of major bleeding compared to rivaroxaban and vitamin K antagonists, while showing similar bleeding risks to apixaban and dabigatran.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of clinical outcomes of edoxaban versus apixaban, dabigatran, rivaroxaban, and vitamin K antagonists in patients with atrial fibrillation in Germany: A real-world cohort study. Marston, XL., Wang, R., Yeh, YC., et al.[2022]

Apixaban, an oral direct factor Xa inhibitor, has been approved in the EU for preventing venous thromboembolism (VTE) after hip or knee replacement surgeries, demonstrating its efficacy in reducing the risk of blood clots in these patients.

The drug is also undergoing phase III trials for preventing strokes in patients with atrial fibrillation, indicating its potential for broader applications in thrombotic disorders, although development for acute coronary syndromes has been halted.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Apixaban: first global approval. Watson, J., Whiteside, G., Perry, C.[2021]

Dabigatran etexilate is shown to be an effective and safe anticoagulation therapy for patients undergoing atrial fibrillation (AF) ablation, with no embolic complications reported in the study.

The safety outcomes, including the incidence of pericardial tamponade and other complications, were similar between dabigatran etexilate and warfarin groups, suggesting that dabigatran can be a viable alternative to warfarin for this procedure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Usefulness of dabigatran etexilate as periprocedural anticoagulation therapy for atrial fibrillation ablation. Yamaji, H., Murakami, T., Hina, K., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06465706

Assessing the Safety and Efficacy of the LAmbre™ Plus ... The goal of this clinical trial is to demonstrate the safety and efficacy of the LAmbre Plus device in patients with non-valvular atrial fibrillation.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7017553/

Systematic review on left atrial appendage closure with the ... Based on the available published data, the LAmbre™ LAAC has been proven as an effective and safe LAAC device for NVAF patients with a high risk ...

3. jacc.org jacc.org/doi/10.1016/j.jcin.2017.06.072

Percutaneous Left Atrial Appendage Closure With ... - JACC We have shown that LAA closure with the LAmbre device is feasible and has a high short-term procedural success rate. Moreover, follow-up results suggest that ...

4. eurointervention.pcronline.com eurointervention.pcronline.com/article/occlusion-of-large-left-atrial-appendage-using-the-lambre-device-procedural-and-short-term-outcomes

Procedural and short-term outcomes of occluding large left ... The principal finding of this study is that the LAmbre device was feasible and safe in occluding large LAA with an ostium ≥31 mm. This study is the first and ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S0929664624000317

Impact of left atrial appendage orifice diameter on the ... In our study, the implantation success rate was 100 %. These results indicate that LAAC with the LAmbre device has a high success rate, regardless of the LAA ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7769662/

Long-Term Safety and Efficacy of Percutaneous Left Atrial ... Taken together, we demonstrate that execution of LAAC with the LAmbre device has high procedural success and prevents AF-related stroke. However ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37943004/

Left atrial appendage occlusion using the LAmbre device ... LAmbre device placement was successful in 101 patients (98.05%). Mean follow-up was 12.2 months. Five patients (4.95%) developed a new ...