VenoValve® Implant for Venous Insufficiency

(SAVVE Trial)

Recruiting at 30 trial locations

Overseen By Kevin Belteau

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

75 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing the VenoValve System, an artificial valve that is surgically placed in leg veins. It aims to help patients with severe vein valve problems by improving blood flow. The study will check if this treatment is safe and effective. The VenoValve is a new prosthetic venous valve being tested for the first time in humans to treat chronic venous insufficiency.

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 data supports the idea that VenoValve® Implant for Venous Insufficiency is an effective treatment?

The available research shows that the VenoValve® Implant is a promising treatment for chronic venous insufficiency. In a human trial, the VenoValve was tested for its safety and performance, indicating it could be a feasible option for patients with severe forms of the condition. Additionally, the study on patient selection suggests that the VenoValve is most beneficial for those with significant blood flow issues, like chronic venous insufficiency, compared to other conditions. This suggests that the VenoValve may be more effective than other treatments, which often fail or have complications over time. ^{1 2 3 4 5}

What data supports the effectiveness of the VenoValve treatment for venous insufficiency?

Research shows that the VenoValve treatment has been tested in humans and dogs, demonstrating initial safety and performance in humans and maintaining function in dogs for several months. Additionally, a similar treatment using a prosthetic patch showed improvement in a patient with chronic venous insufficiency, suggesting potential benefits of prosthetic valves. ^{1 2 3 4 5}

What safety data is available for the VenoValve® treatment?

The provided research does not contain specific safety data for the VenoValve® treatment or its other names like Hancock-Jaffe bioprosthetic venous valve. The articles focus on other medical devices and treatments, such as the ALLEGRA valve, Janus kinase inhibitors, and adalimumab biosimilars. Therefore, no relevant safety data for VenoValve® is available in the given research. ^{6 7 8 9 10}

Is the VenoValve® treatment a promising option for venous insufficiency?

Yes, the VenoValve® treatment is promising because it offers a new option for patients with severe venous insufficiency, a condition where blood struggles to return from the legs to the heart. Current treatments often fail, but the VenoValve® has shown potential in early studies to improve blood flow and quality of life for patients. ^{1 2 3 11 12}

How is the VenoValve treatment different from other treatments for venous insufficiency?

The VenoValve is unique because it is a prosthetic venous valve designed to replace faulty valves in the veins, which is a novel approach for treating chronic venous insufficiency. Unlike other treatments, it specifically targets the mechanical failure of the venous valves, aiming to restore normal blood flow from the legs to the heart. ^{1 2 3 11 12}

Research Team

Marc Glickman, MD

Principal Investigator

Hancock Jaffe Laboratories, Inc

Eligibility Criteria

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

I am 18 years old or older.

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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 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]

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 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]

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]

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 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]

References

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

Human trial using the novel bioprosthetic VenoValve in patients with chronic venous insufficiency. [2022]

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

Prosthetic venous valve patient selection by validated physics-based computational models. [2018]

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

Experimental prosthetic vein valve. [2019]

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

Femoral vein valve incompetence: treatment with a xenograft monocusp patch. Preliminary report. [2012]

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

Role of vessel-to-prosthesis size mismatch in venous valve performance. [2018]

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

Novel self-expanding ALLEGRA transcatheter aortic valve for native aortic stenosis and degenerated bioprosthesis. [2022]

7. Canada pubmed.ncbi.nlm.nih.gov

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

8. England 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). [2022]

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

Postmarketing safety of biologics and biological devices. [2018]

10. England 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. [2015]

11. England pubmed.ncbi.nlm.nih.gov

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

12. China pubmed.ncbi.nlm.nih.gov

[Substitute valve at popliteal vein in treating deep venous valve insufficiency of lower extremities]. [2006]