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

2931 Participants Needed

Trial Summary

What is the purpose of this trial?

The primary objective is to demonstrate the safety and efficacy of the implantation of the LAmbre PlusTM device in patients with large or irregularly shaped appendages with non-valvular atrial fibrillation who are at increased risk for stroke and systemic embolism compared to oral anticoagulation (OAC).

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 data supports the effectiveness of the Lambre Device for Atrial Fibrillation treatment?

Research shows that drugs like edoxaban, apixaban, and rivaroxaban are effective in preventing strokes in patients with atrial fibrillation, often performing as well as or better than warfarin, a traditional treatment. This suggests that the Lambre Device treatment, which involves these drugs, may also be effective for atrial fibrillation. ^{1 2 3 4 5}

Is the Lambre Device for Atrial Fibrillation safe for humans?

The safety of various oral anticoagulants like apixaban, dabigatran, rivaroxaban, and edoxaban has been studied, showing they are generally safe for preventing blood clots in conditions like atrial fibrillation, though they carry a risk of bleeding. These medications are used to prevent strokes and treat blood clots, and safety measures include educational materials to minimize bleeding risks. ^{1 6 7 8 9}

What makes the Lambre Device treatment for atrial fibrillation unique compared to other drugs?

The Lambre Device treatment for atrial fibrillation is unique because it combines the use of a specialized device with anticoagulant drugs like Apixaban, Dabigatran, and Warfarin, which are typically used to prevent blood clots. This combination may offer a novel approach by potentially enhancing the effectiveness of stroke prevention in patients with atrial fibrillation. ^{10 11 12 13 14}

Research Team

Brian O'Neill, MD

Principal Investigator

Henry Ford Health System

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

References

1. Netherlands 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. [2022]

2. Germany 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. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Edoxaban therapy increases treatment satisfaction and reduces utilization of healthcare resources: an analysis from the EdoxabaN vs. warfarin in subjectS UndeRgoing cardiovErsion of atrial fibrillation (ENSURE-AF) study. [2019]

4. England pubmed.ncbi.nlm.nih.gov

Representativeness of the dabigatran, apixaban and rivaroxaban clinical trial populations to real-world atrial fibrillation patients in the United Kingdom: a cross-sectional analysis using the General Practice Research Database. [2021]

5. Japan pubmed.ncbi.nlm.nih.gov

Clinical factors related to successful or unsuccessful cardioversion in the EdoxabaN versus warfarin in subjectS UndeRgoing cardiovErsion of Atrial Fibrillation (ENSURE-AF) randomized trial. [2023]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Apixaban: first global approval. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

Betrixaban: A New Oral Factor Xa Inhibitor for Extended Venous Thromboembolism Prophylaxis in High-Risk Hospitalized Patients. [2019]

8. New Zealand pubmed.ncbi.nlm.nih.gov

Evaluating the Effectiveness of Apixaban Additional Risk Minimisation Measures Using Surveys in Europe. [2021]

9. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Pharmacologic properties of the new oral anticoagulants: a clinician-oriented review with a focus on perioperative management. [2022]

10. New Zealand pubmed.ncbi.nlm.nih.gov

Usefulness of dabigatran etexilate as periprocedural anticoagulation therapy for atrial fibrillation ablation. [2021]

11. Australia pubmed.ncbi.nlm.nih.gov

The Bosentan Patient Registry: long-term survival in pulmonary arterial hypertension. [2018]

12. Denmark pubmed.ncbi.nlm.nih.gov

[Blockade of endothelin receptor with bosentan--a new principle of treatment in pulmonary arterial hypertension]. [2018]

13. New Zealand pubmed.ncbi.nlm.nih.gov

Investigation of the effect of macitentan on the pharmacokinetics and pharmacodynamics of warfarin in healthy male subjects. [2021]

14. Switzerland pubmed.ncbi.nlm.nih.gov

Efficacy and safety of switching from bosentan or ambrisentan to macitentan in pulmonary arterial hypertension: A systematic review and meta-analysis. [2023]