BlueLeaf System for Chronic Venous Insufficiency

(INFINITE-US Trial)

No longer recruiting at 4 trial locations

Overseen By Kristine Orosz, BS

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Intervene, Inc.

Must not be taking: Oral contraceptives, others

Disqualifiers: DVT, Heart failure, Infection, others

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

Compensation: Varies

Number of Visits: 2

Duration: Procedure day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new device called the BlueLeaf® Endovenous Valve Formation System to treat chronic venous insufficiency (CVI) in the legs. CVI occurs when blood doesn't flow back to the heart properly, causing symptoms like pain and swelling. The trial aims to determine if the BlueLeaf System can improve these symptoms. Individuals with CVI symptoms that haven't improved with other treatments for at least six months might be suitable candidates for this trial. As an unphased trial, it offers patients the chance to explore innovative treatment options that might not yet be widely available.

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, if you have untreated significant superficial venous incompetence or contraindications to anticoagulation, you may not be eligible. It's best to discuss your specific medications with the trial team.

What prior data suggests that the BlueLeaf System is safe for treating chronic venous insufficiency?

Research has shown that the BlueLeaf Endovenous Valve Formation System safely creates new valves in veins. This system is minimally invasive, requiring no large cuts or implants. Studies have found that veins treated with the BlueLeaf System remain open, indicating positive safety outcomes. Earlier studies reported that the device was well-tolerated, with no major safety issues. This suggests it could be a safe option for individuals with chronic venous insufficiency, a condition where leg veins struggle to return blood to the heart. Overall, the BlueLeaf System appears to be a promising and safe treatment under study. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard treatments for chronic venous insufficiency, which often involve surgical interventions or stenting, the BlueLeaf® Endovenous Valve Formation System offers a novel approach by forming valves in situ within the vein. This method is minimally invasive and aims to restore proper blood flow without the need for implants or extensive surgery. Researchers are excited about this technique because it has the potential to provide a more natural and less invasive solution, potentially leading to quicker recovery times and fewer complications for patients.

What evidence suggests that the BlueLeaf System is effective for treating chronic venous insufficiency?

Research has shown that the BlueLeaf Endovenous Valve Formation System, which trial participants will receive, could be a promising treatment for chronic venous insufficiency (CVI) in the lower leg. One study found that 93% of patients successfully developed at least one valve using this system. Another study reported that after a year, 97% of these valves remained open and functioning well. The BlueLeaf System creates these valves without implants, avoiding potential complications. These findings suggest the treatment could be effective for people with CVI. ^{1 3 4 5 6}

Who Is on the Research Team?

Jeff Elkins

Principal Investigator

Intervene, Inc.

Are You a Good Fit for This Trial?

Inclusion Criteria

You have tried conservative treatments for at least 6 months to manage your condition, but the symptoms did not improve or you were unable to continue the treatment.

Deep system venous reflux characterized by >1 second reflux time in two vein segments (vein segments defined as: proximal femoral, distal femoral, and popliteal), as assessed by duplex ultrasound (DUS) with patient in the standing position

Presence of at least two potential target sites within a target vessel as assessed preliminarily by DUS, with a target site being defined as a segment within the femoral or popliteal vein that is: 7mm to 11mm in luminal diameter and at least 3cm long and absent features that, in the Investigator's opinion, would preclude formation of a monocuspid valve (at any orientation)

Exclusion Criteria

You have a history of heart failure specifically affecting the right side of your heart, which can be caused by different conditions that increase pressure in the right side of the heart.

Non-ambulatory patients

You are unable to take any of the recommended blood thinning medications listed in the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Subjects are treated with the BlueLeaf System for the formation of autogenous vein valves

Procedure day

1 visit (in-person)

Initial Follow-up

Participants are monitored for safety and effectiveness of the procedure

30 days

1 visit (in-person)

Extended Follow-up

Participants are monitored for changes in Venous Clinical Severity Score (rVCSS) and long-term safety

1 year

Periodic visits (in-person)

Long-term Follow-up

Participants are monitored for safety and effectiveness up to 5 years

5 years

What Are the Treatments Tested in This Trial?

Interventions

• BlueLeaf® Endovenous Valve Formation System

How Is the Trial Designed?

Group I: Investigational Experimental Treatment 1 Intervention

Subjects will be treated with the investigational device and followed per protocol.

Who Is Running the Clinical Trial?

Intervene, Inc.

Lead Sponsor

Trials

4

Recruited

30+

Published Research Related to This Trial

In a study of 67 patients with iliofemoral chronic venous disease, the novel blueflow Venous Stent showed a high primary patency rate of 91.7% at 6 months and 79.8% at 12 months, indicating its effectiveness in treating venous outflow obstruction.

Patients experienced significant clinical improvements, with a median reduction in the revised venous clinical severity score (rVCSS) from 8 to 4 over 12 months, and no major safety concerns were reported, suggesting the stent is a safe option for this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Braided nitinol stent for chronic iliofemoral venous disease - the real-world BLUEFLOW registry. Lichtenberg, M., Stahlhoff, S., Özkapi, A., et al.[2021]

In a study of 308 lower limbs treated with the 1470 nm diode laser for varicose veins, the endovenous laser ablation showed a remarkable 99.6% success rate in eliminating venous reflux after one year.

The treatment was found to be safe, with no cases of deep vein thrombosis or pulmonary embolism, and only a low recurrence rate of varicose veins at 2.81%, indicating both high efficacy and safety for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Endovenous laser ablation of varicose veins with the 1470 nm diode laser using a radial fiber - 1-year follow-up. von Hodenberg, E., Zerweck, C., Knittel, M., et al.[2016]

In a study involving 14 patients with chronic venous insufficiency, the BlueLeaf System successfully formed at least one deep venous valve in 93% of cases, demonstrating its efficacy as a minimally invasive treatment option.

There were no serious adverse events or deep venous thromboses reported during the study, indicating a high safety profile for the BlueLeaf System over a 1-year follow-up period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and feasibility report on nonimplantable endovenous valve formation for the treatment of deep vein reflux. Vasudevan, T., Robinson, DA., Hill, AA., et al.[2022]

Endovenous laser ablation (EVLA) demonstrated a high success rate, with 96% of treated veins showing complete occlusion after three months in a study of 631 patients.

The procedure is considered safe, with only one non-fatal pulmonary embolism reported and no other complications, indicating that EVLA can be effectively performed with proper training and skill acquisition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Introducing endovenous laser therapy ablation to a national health service vascular surgical unit - the Aberdeen experience. Mackenzie, RK., Cassar, K., Brittenden, J., et al.[2016]

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S2213333X20307289

Safety and feasibility report on nonimplantable ... Key Findings: Endovenous venous valve formation in patients with severe chronic venous insufficiency and deep vein reflux was feasible with the BlueLeaf System.

2. evtoday.com evtoday.com/articles/2025-july/endovenous-valves-from-the-present-to-the-near-future

Endovenous Valves: From the Present to the Near Future Results were quite good: 1-year valve patency was 97%, VCSS ... Initial US experience with the BlueLeaf endovenous valve formation system.

3. clinicaltrials.gov clinicaltrials.gov/ct2/show/NCT04225806

Investigation of Femoropopliteal In Situ Valve Formation ... The purpose of this early feasibility study is to provide information on the BlueLeaf System for the formation of one or more autogenous vein ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33359385/

Safety and feasibility report on nonimplantable ... Results: Of the 14 patients, 13 (93%) had successful formation of at least one monocuspid valve, with a mean number of 1.4 valves (range, 0-3 valves) per ...

5. jvsvenous.org jvsvenous.org/article/S2213-333X(20)30728-9/pdf

Safety and feasibility report on nonimplantable ... The BlueLeaf System provides an endovenous method for the formation of deep venous valves without an implant, avoiding the complications associated with ...

6. symplr.com symplr.com/publication/blueleaf-endovenous-valve-formation-evf-system-for-chronic-venous-insufficiency

BlueLeaf Endovenous Valve Formation (EVF) System for ... The BlueLeaf Endovenous Valve Formation (EVF) System is an endovascular device intended to form autogenous tissue leaflets from femoral and popliteal vein ...