VenoValve® Implant for Venous Insufficiency

(SAVVE Trial)

Not currently recruiting at 31 trial locations

Overseen By NavYash Gupta, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Hancock Jaffe Laboratiores, Inc

Must not be taking: Narcotics, Anticoagulants

Disqualifiers: Superficial reflux, Untreated iliac obstruction, Hypercoagulable condition, 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment, the VenoValve, for individuals with deep vein issues in their legs. The goal is to determine if this tiny valve, when surgically placed in the vein, can safely improve blood flow and reduce symptoms such as swelling or sores. The trial seeks participants who have tried standard treatments, like compression socks, for at least three months without success and have significant vein problems.

As an unphased trial, this study provides patients the opportunity to explore innovative solutions beyond standard treatments.

Do I have to stop taking my current medications for the VenoValve trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you must be able to comply with a post-operative anticoagulation regimen, and certain conditions like chronic narcotic usage or untreated hypercoagulable conditions may affect eligibility.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, you must be able to comply with a post-operative anticoagulation regimen, so discuss your current medications with the trial team.

What prior data suggests that the VenoValve® is safe for treating venous insufficiency?

Research has shown that the VenoValve, a special valve for treating vein problems, has been tested in people with positive safety results. In one study, 73 out of 75 patients successfully received the VenoValve, indicating it is generally well-tolerated. Over three years, the VenoValve remained safe and effective for patients. Another study followed eight patients for two years and confirmed similar safety results. These findings suggest that the VenoValve is safe to use, with no major safety issues reported in these studies. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard treatments for venous insufficiency, which often include compression therapy or surgical options like vein stripping, the VenoValve® is unique because it introduces a bioprosthetic valve directly into the vein. This new approach aims to restore proper blood flow by replacing the faulty natural valve, potentially offering a more lasting solution. Researchers are excited about the VenoValve® because it targets the root cause of venous insufficiency by directly addressing valve failure, rather than just managing symptoms. This could lead to significant improvements in patient outcomes and quality of life.

What evidence suggests that the VenoValve is effective for venous insufficiency?

Research has shown that the VenoValve® device, which trial participants will receive, may help treat deep vein valve problems. One study reported a 54% decrease in the time for blood to flow correctly in the veins, indicating more efficient blood movement. Another study found a 40% improvement in blood flow, reflecting better vein function. Patients experienced significant improvements in their condition, suggesting enhanced overall health. These findings suggest that the VenoValve® could effectively improve blood flow for patients with this condition. ^{6 7 8 9 10}

Who Is on the Research Team?

Marc Glickman, MD

Principal Investigator

Hancock Jaffe Laboratories, Inc

Are You a Good Fit for This Trial?

This trial is for adults over 18 with severe leg vein problems (C4b-C6) who haven't improved after 3 months of standard care. They must be able to have an ultrasound, walk unaided, not be pregnant or breastfeeding, agree to birth control if applicable, and have a BMI under 40. People can't join if they've had recent blood clots, other trials within 30 days, certain vein procedures within six weeks, untreated major vein blockages, specific heart conditions or sensitivities to materials in the device.

Inclusion Criteria

I have tried standard treatments like compression therapy for over 3 months without success.

Willing and able to comply with all compulsory study procedures and provide informed consent prior to any study procedures being performed

The blood takes too long to flow through a specific vein in your leg.

Exclusion Criteria

You regularly use strong pain medications for a long time.

My blood flow through arteries in my legs is significantly reduced.

I have a stent in the vein of my thigh or knee area.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive the VenoValve implant through an open surgical technique

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Multiple visits at 30 days, 3, 6, 12 months, and annually thereafter

What Are the Treatments Tested in This Trial?

Interventions

• Hancock-Jaffe bioprosthetic venous valve (VenoValve®)

Trial Overview

The study tests the VenoValve®, a bioprosthetic valve surgically placed into deep veins as a treatment for patients whose leg veins don’t close properly causing swelling and ulcers. It's a single-group study where all participants receive the valve to see how safe and effective it is.

How Is the Trial Designed?

Group I: VenoValve Experimental Treatment 1 Intervention

Subjects who receive VenoValve implant

Hancock-Jaffe bioprosthetic venous valve (VenoValve®) is already approved in United States for the following indications:

Approved in United States as VenoValve for:

• Under investigation for deep venous valvular insufficiency (C4b-C6 patients); not yet approved

Who Is Running the Clinical Trial?

Hancock Jaffe Laboratiores, Inc

Lead Sponsor

Trials

1

Recruited

80+

Syntactx

Collaborator

Trials

23

Recruited

1,147,000+

AXIOM Real Time Metrics

Collaborator

Trials

4

Recruited

750+

Published Research Related to This Trial

The VenoValve, a prosthetic venous valve, was successfully implanted in 10 patients with severe chronic venous insufficiency (C5-C6), achieving a 100% technical success rate and showing promising early results in improving clinical outcomes and quality of life after 6 months.

Patients demonstrated significant improvements, including a 61% decrease in venous clinical severity scores and a 57% decrease in pain scores, indicating that the VenoValve may be an effective treatment option for those suffering from severe CVI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human trial using the novel bioprosthetic VenoValve in patients with chronic venous insufficiency. Ulloa, JH., Glickman, M.[2022]

A new prosthetic vein valve was successfully implanted in 10 dogs without the use of anticoagulants, showing promising results for treating venous insufficiency.

After 3 to 8 months, the prosthetic valves maintained patency and competency, indicating potential for effective long-term use in managing venous insufficiency.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Experimental prosthetic vein valve. Taheri, SA., Rigan, D., Wels, P., et al.[2019]

A new prosthetic vein valve design effectively prevents regurgitation and reduces venous reflux, showing promising results in a mock-up and prototype testing with low regurgitation values compared to no device.

The valve maintains normal antegrade flow without increasing resistance, indicating its potential as a viable surgical treatment option for chronic venous insufficiency, warranting further in vivo testing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The design, development, and evaluation of a prototypic, prosthetic venous valve. Oberdier, MT., Rittgers, SE.[2018]

In a study of 27 patients with deep venous valve insufficiency, the use of a substitute valve at the popliteal vein significantly reduced ambulatory venous pressure from an average of 9.14 kPa to 5.94 kPa after surgery, indicating improved venous function.

After a follow-up period of 2-6 years, 21 out of 27 patients reported satisfactory results, suggesting that this treatment is effective and has potential for widespread application in managing venous insufficiency.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Substitute valve at popliteal vein in treating deep venous valve insufficiency of lower extremities]. Yin, LP., Feng, C., Gu, Y.[2006]

The ALLEGRA aortic valve, used in 93 patients for aortic valve stenosis or degenerated valve prosthesis, demonstrated a high implantation success rate of 97.8% and a device success rate of 94.6%, indicating its efficacy in routine clinical use.

The procedure had a low complication rate, with in-hospital all-cause mortality at 2.2% and only minor instances of paravalvular leakage, suggesting that the ALLEGRA valve is both safe and effective for patients, particularly those with a mean age of 82.5 years.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel self-expanding ALLEGRA transcatheter aortic valve for native aortic stenosis and degenerated bioprosthesis. Neuser, J., Kempf, T., Bauersachs, J., et al.[2022]

Janus kinase inhibitors (JAKi) are commonly used for treating immune-mediated inflammatory diseases like psoriatic arthritis, but recent studies have raised safety concerns, particularly in patients over 50 with cardiac risk factors.

This review summarizes the latest safety data for various JAKi, including tofacitinib and upadacitinib, and discusses findings from an oral surveillance study to provide context for these safety issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Janus Kinase Inhibitors: Safety in Patients With Psoriatic Arthritis. Nash, P.[2022]

Prosthetic venous valves that are mismatched in size by more than 15% significantly increase regurgitate volume, closing time, and pressure differences, which can negatively impact valve function.

To optimize the performance of venous valves and reduce wall stress, it is crucial that the size of the prosthetic valve is within 15% of the maximum vein size, as larger mismatches can double or triple the wall stress compared to normal physiological levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of vessel-to-prosthesis size mismatch in venous valve performance. Tien, WH., Zhao, X., Chen, HY., et al.[2018]

The study identified that patients with chronic venous insufficiency (CVI) classes 4 to 6, right heart hypertrophy (RHH), and right heart failure (RHF) are the most likely to benefit from a venous valve prosthesis, as simulations showed a significant reduction in mechanical stress ratios for these groups.

Conversely, patients with deep venous thrombosis (DVT) are least likely to benefit from the prosthetic valve due to low flow conditions, although the valve may be useful for post-thrombotic patients after thrombus removal and flow restoration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prosthetic venous valve patient selection by validated physics-based computational models. Chen, HY., Berwick, ZC., Kemp, A., et al.[2018]

A study analyzing 741 adverse events reported for three biologics (adalimumab, etanercept, and infliximab) in the Portuguese pharmacovigilance system found that all three were significantly associated with increased risks of infections and neoplasms, indicating potential safety concerns.

Adalimumab and etanercept showed strong associations with specific adverse events, while infliximab was linked to a broader range of issues, including immune system disorders and respiratory problems, suggesting that each biologic may have unique safety profiles that require careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety profiles of adalimumab, etanercept and infliximab: a pharmacovigilance study using a measure of disproportionality in a database of spontaneously reported adverse events. Mendes, D., Alves, C., Batel-Marques, F.[2015]

A 36-year-old woman with chronic venous insufficiency successfully underwent venous valve reconstruction using prosthetic bovine monocusp patches, indicating a promising surgical intervention for this condition.

Postoperative assessments, including Doppler studies and phlebography, showed restored valvular competence and significant clinical improvement after 15 months, demonstrating the efficacy of the procedure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Femoral vein valve incompetence: treatment with a xenograft monocusp patch. Preliminary report. Garcia-Rinaldi, R., Revuelta, JM., Martinez, MJ., et al.[2012]

The study demonstrated that AVT02, an adalimumab biosimilar, is bioequivalent to both the EU- and US-approved reference products, with pharmacokinetic parameters falling within the acceptable range of 80% to 125% for bioequivalence.

Safety and immunogenicity profiles of AVT02 were found to be comparable to those of the reference products, indicating that it is a safe alternative for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized, adaptive design, double-blind, 3-arm, parallel study assessing the pharmacokinetics and safety of AVT02, a high-concentration (100 mg/mL) Adalimumab biosimilar, in healthy adult subjects (ALVOPAD FIRST). Wynne, C., Schwabe, C., Lemech, C., et al.[2022]

Postmarketing safety surveillance is essential for identifying rare adverse events and complications associated with biologics and biological devices that may not be detected during premarketing studies.

Adverse event reporting has led to important safety notifications and label changes, highlighting risks such as airway compromise from bone morphogenetic protein and fatal air embolisms from fibrin sealants, underscoring the need for ongoing monitoring of these products.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Postmarketing safety of biologics and biological devices. Woo, EJ.[2018]

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The VenoValve is a porcine based bioprosthetic device that is implanted in the deep femoral vein of the leg to treat a condition called Chronic ...

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The objective of this study is to assess the safety and effectiveness of the VenoValve System for the treatment of patients with deep venous ...

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This study provides 2-year outcomes for 8 patients who were implanted with the bioprosthetic VenoValve for treating severe CVI with deep venous reflux.

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Conclusion. VenoValve implantation demonstrated mid-term safety and efficacy in restoring deep venous competence in patients with refractory PTS, leading to ...

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Implantation of the bioprosthetic venous valve device into the femoral vein successfully performed in 73 of 75 patients (97.3%), and meaningful ...

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Promising results from the first-in-human study demonstrated that, at three-years post implantation, VenoValve remained safe and effective.