Amplatzer Plug for Aortic Regurgitation

(PARADIGM Trial)

Recruiting at 30 trial locations

Overseen By Leslie Centeno

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Abbott Medical Devices

Disqualifiers: Rocking valve, Hemodynamic instability, Active infection, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 31

Duration: 1 day

200 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effectiveness of a small medical device called the Amplatzer Valvular Plug III. The device aims to fix leaks around heart valves, which can cause heart failure symptoms or require frequent blood transfusions. People with a mechanical or biological heart valve experiencing significant leaks might be good candidates. Participants must have one leak that can be fixed with a single plug and exhibit symptoms like those mentioned.

As an unphased trial, this study offers patients the chance to contribute to important research that could enhance treatment options for heart valve leaks.

Do I need to stop my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications. Please consult with the trial coordinators for more details.

What prior data suggests that the Amplatzer Valvular Plug III is safe for treating paravalvular leaks?

Research has shown that the Amplatzer Valvular Plug III is a safe option for fixing leaks around heart valves. Studies indicate it successfully seals leaks in 93% of patients. In one study, 141 out of 142 leaks were fixed, with most resolved on the first attempt. This outcome suggests the device is well-accepted by patients. No major reports of serious side effects have emerged, indicating it is generally safe for use. ^{1 2 3 4 5}

Why are researchers excited about this trial?

The Amplatzer Valvular Plug III is unique because it offers a minimally invasive approach to addressing aortic regurgitation due to paravalvular leaks, which are challenging to treat with traditional surgical methods like valve replacement or repair. This plug is specifically designed to seal leaks around the edges of a valve implant, targeting areas that are difficult to access and fix with current techniques. Researchers are excited about this treatment because it simplifies the procedure, potentially reducing recovery time and improving outcomes for patients who might not be ideal candidates for surgery.

What evidence suggests that the Amplatzer Valvular Plug III is effective for treating paravalvular leaks?

Research has shown that the Amplatzer Valvular Plug III, which participants in this trial will receive, effectively treats leaks around replacement heart valves, known as paravalvular leaks (PVL). Studies have found that it successfully closes these leaks in over 90% of patients within 30 days. Specifically, one study demonstrated that 141 out of 142 leaks were closed successfully, highlighting its high success rate. The treatment is safe and works well with both mechanical and biological heart valves, making it a promising option for those with significant PVL issues. ^{1 2 3 6 7}

Who Is on the Research Team?

Carlos Ruiz, MD

Principal Investigator

Hackensack Meridian Health

Are You a Good Fit for This Trial?

This trial is for adults over 18 with a mechanical or biological heart valve in the aortic or mitral position and significant paravalvular leak causing heart issues or needing blood transfusions. Not eligible if pregnant, nursing, have limited life expectancy, unstable health, other conflicting conditions, or are in another drug/device study.

Inclusion Criteria

Subject has provided written informed consent

I have a mechanical or biological valve implant in my heart.

Note: Subjects in European countries can only be implanted with a mechanical valve in the aortic or mitral position

Exclusion Criteria

My veins are not suitable for AVP III delivery.

I have leaking around my artificial heart valves.

I cannot have surgery because my heart and blood circulation are not stable.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo an AVP III implant procedure for PVL closure

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

Visits at Discharge, 30 days, 6 months, and 1 year

What Are the Treatments Tested in This Trial?

Interventions

• Amplatzer Valvular Plug III

Trial Overview The PARADIGM study tests the safety and effectiveness of the Amplatzer Valvular Plug III (AVP III) to treat leaks around surgical heart valves. It's a forward-looking single-group study involving multiple centers.

How Is the Trial Designed?

Group I: Paravalvular Leak Closure Experimental Treatment 1 Intervention

Includes all eligible subjects who undergo an AVP III implant attempt for treatment of significant paravalvular leakage with an echocardiographic severity grade of moderate or higher. This is a single arm study.

Amplatzer Valvular Plug III is already approved in European Union, United States for the following indications:

Approved in European Union as Amplatzer Valvular Plug III for:

• Closure of paravalvular leaks (PVLs) following surgical implant of a mechanical or biological heart valve implanted in the aortic or mitral position

Approved in United States as Amplatzer Valvular Plug III for:

• Closure of paravalvular leaks (PVLs) following surgical implant of a mechanical or biological heart valve implanted in the aortic or mitral position

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

The Amplatzer Vascular Plug (AVP) is a safe and effective device for occluding peripheral vessels during endovascular abdominal aortic aneurysm repair, with low complication rates such as buttock claudication and endoleaks.

Compared to traditional coil embolization, the AVP not only reduces the risk of complications but also significantly lowers procedural costs, averaging US$310 for the AVP versus US$2262 for coils.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The use of the Amplatzer Vascular Plug in the prevention of endoleaks during abdominal endovascular aneurysm repair: A systematic literature review on current applications. Bracale, UM., Petrone, A., Provenzano, M., et al.[2022]

The Amplatzer Vascular Plug (AVP) was successfully used in a study of six patients to treat vascular complications related to hemodialysis access, achieving 100% technical success in occluding problematic arteriovenous fistulas and grafts.

All patients experienced immediate improvement in distal arterial flow and resolution of clinical symptoms, with no procedure-related complications reported, highlighting the AVP's safety and efficacy as a minimally invasive treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amplatzer vascular plug for arteriovenous hemodialysis access occlusion: initial experience. Bui, JT., Gaba, RC., Knuttinen, MG., et al.[2019]

An Amplatzer vascular plug II (AVP) was successfully used to occlude an aortic sac in a patient with an infrarenal aortic aneurysm after initial surgical ligation failed, demonstrating its effectiveness in this novel application.

The procedure involved placing the AVP in conjunction with coil embolization of lumbar arteries, and follow-up CT confirmed successful occlusion of the sac, highlighting the AVP's versatility as an embolic device.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of an Amplatzer vascular plug II for aortic sac occlusion after failed surgical ligation. Tam, MD., Morrow, D., Crawford, MB.[2016]

In a study of 50 patients with congenital cardiovascular disease, the Amplatzer vascular plugs (plug 1 and plug 2) demonstrated 100% effectiveness in achieving complete occlusion of targeted blood vessels, highlighting their efficacy in vascular occlusion procedures.

The use of these plugs was associated with a low complication rate of only 3.8%, indicating that they are safe for use in a variety of vascular structures, particularly plug 2 for high-flow conditions like type C patent ductus arteriosus.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Amplatzer vascular plug and Amplatzer vascular plug II for vascular occlusion procedures in 50 patients with congenital cardiovascular disease. Schwartz, M., Glatz, AC., Rome, JJ., et al.[2012]

In a study involving 31 patients, 39 Amplatzer vascular plugs (AVPs) were successfully implanted, achieving a 92% deployment success rate and complete occlusion of the target vessels within 10 minutes, demonstrating their efficacy in treating various congenital cardiovascular malformations.

The use of AVPs was found to be safe, with no procedure-related complications reported, highlighting their reliability as a treatment option for closing medium-to-large vascular communications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amplatzer vascular plugs in congenital cardiovascular malformations. Barwad, P., Ramakrishnan, S., Kothari, SS., et al.[2022]

In an in-vitro study testing Amplatzer devices for closing paravalvular leaks (PVL) after transcatheter aortic valve implantation, the devices showed a maximum efficiency of less than 50% in reducing PVL, indicating limited effectiveness.

The study found that the vascular plugs interfered with the leaflets of the prosthetic valve, suggesting that currently used devices may compromise the valve's structural integrity, highlighting the need for specifically designed occluders for this purpose.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vitro hemodynamic testing of Amplatzer plugs for paravalvular leak occlusion after transcatheter aortic valve implantation. Burriesci, G., Peruzzo, P., Susin, FM., et al.[2022]

The Amplatzer Vascular Plug (AVP) is an effective embolic device for occluding medium to large vessels, but there is a risk of migration, as demonstrated in a case where a 6-mm AVP migrated from the common hepatic artery to the proper hepatic artery during a procedure for pancreatic cancer.

In cases where retrieval of a migrated AVP is not feasible, delivering the device to a less critical artery, such as the splenic artery, can be a viable alternative to achieve complete occlusion, as shown by the successful redeployment of a 10-mm AVP in this case.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcatheter retrieval of an Amplatzer Vascular Plug. Sato, Y., Inaba, Y., Hasegawa, T., et al.[2022]

In a study of seven patients, the Amplatzer vascular II Plug (AVPII) was successfully used for the percutaneous closure of small patent ductus arteriosus, achieving adequate occlusion in 6 out of 7 cases.

The procedure demonstrated safety, with only one major complication reported, and confirmed complete occlusion through echocardiography within 24 hours, indicating the AVPII is an effective option for this type of closure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Percutaneous closure of patent ductus arteriosus using the Amplatzer vascular Plug II]. Parra-Bravo, R., Beirana-Palencia, L., Corona-Rodríguez, A., et al.[2011]

Citations

1. cardiovascular.abbott cardiovascular.abbott/int/en/hcp/products/structural-heart/structural-interventions/amplatzer-valvular.html

Amplatzer™ Valvular Plug III As such, the Amplatzer Valvular Plug III can provide effective closure in over 90% of patients at 30 day follow up.6,7,8. A Solution To A Key Issue. Around the ...

2. structuralheart.abbott structuralheart.abbott/int/products/paravalvular-leak/amplatzer-valvular-plug/clinical-data

Amplatzer Valvular Plug III (PVL) Clinical Data Clinical studies continue to show that the Amplatzer Valvular Plug III is a highly effective solution in closing PVL near mechanical surgical valves.

3. sciencedirect.com sciencedirect.com/science/article/pii/S0828282X25010700

Multiple Amplatzer Vascular Plug III implantation–feasible ... Successful leak closure was achieved in 141 out of 142 leaks, with 131 occluded at the first (technical success 93%) and 10 at the second ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/25037539/

Paravalvular leak closure with the Amplatzer Vascular Plug ... Mitral and aortic paravalvular leak closure with the Amplatzer Vascular Plug III is feasible and safe, with high clinical and echocardiographic success rates.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04489823

PARADIGM: Amplatzer Valvular Plug for PVL Closure The Paradigm study is a prospective, multicenter, single arm study to demonstrate the safety and effectiveness of the Amplatzer Valvular Plug III (AVP III)

6. my-connext.com my-connext.com/fileadmin/connext/downloads-trending/PVL/files/amplatzer-valvular-plug-III-hcp.pdf

CLOSES LEAKS OPENS OPPORTUNITIES AMPLATZER™ VALVULAR PLUG III (FORMERLY AVP III). ONE-CLASS IMPROVEMENT IN. THE NYHA CLASSIFICATION IN. UP TO 90% OF PATIENTS1,2,3,4. CLOSES LEAKS. OPENS ...

7. structuralheart.abbott structuralheart.abbott/int/products/paravalvular-leak/amplatzer-valvular-plug

Amplatzer Valvular Plug III (PVL) | Paravalvular leaks As such, the Amplatzer Valvular Plug III can provide effective closure in up to 93% of patients.1, 5, 6. PATIENTS WHO BENEFIT. A solution to a key issue. Around ...