Bioresorbable Arterial Scaffold for Peripheral Artery Disease

(RESOLV I Trial)

Recruiting at 6 trial locations

Overseen By Andrew J Ford, Jr.

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: R3 Vascular Inc.

Must be taking: Antiplatelet medications

Must not be taking: Immunosuppressive medications

Disqualifiers: Pregnancy, Renal insufficiency, Stroke, others

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 1 day

30 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests a new dissolvable stent for patients with severe leg artery blockages. The stent helps improve blood flow, releases medicine to prevent re-blockage, and then dissolves gradually. This could reduce pain and lower the risk of amputation. Bioabsorbable stents have been extensively evaluated in coronary artery disease but remain challenging and less studied in lower extremities.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on antiplatelet medications, you should not have any planned surgery or procedure that requires stopping these medications within 6 months after the procedure.

What data supports the effectiveness of the MAGNITUDE® Bioresorbable Arterial Scaffold treatment for Peripheral Artery Disease?

Research on similar bioresorbable scaffolds, like the Absorb scaffold, shows promising results in maintaining open blood vessels in complex artery conditions, with good long-term outcomes. Additionally, studies on bioresorbable scaffolds highlight their ability to provide temporary support and controlled drug release, which helps in healing and reducing artery narrowing. ^{1 2 3 4 5}

Is the MAGNITUDE Bioresorbable Arterial Scaffold safe for humans?

Bioresorbable scaffolds, like the MAGNITUDE, are designed to provide temporary support to blood vessels and then gradually dissolve, reducing long-term risks associated with permanent implants. Studies have shown that these scaffolds are generally safe, with good healing responses observed in animal models and positive outcomes reported in human trials for similar devices. ^{1 2 3 6 7}

What makes the MAGNITUDE® Bioresorbable Arterial Scaffold treatment unique for peripheral artery disease?

The MAGNITUDE® Bioresorbable Arterial Scaffold is unique because it is designed to be absorbed by the body over time, unlike traditional metal stents that remain permanently. This feature may reduce long-term complications and the need for future interventions. ^{8 9 10 11 12}

Research Team

Juan F Granada, MD

Principal Investigator

Cardiovascular Research Foundation (CRF)

Eligibility Criteria

This trial is for adults aged 18-90 with severe peripheral arterial disease, causing leg pain or risk of limb amputation. Participants must have specific types of blockages in their lower leg arteries and agree to follow-up visits over five years. Pregnant individuals, those with recent major cardiovascular events, uncontrolled diabetes, known allergies to device materials or study medications, prior below-the-knee bypasses or stents in the target vessel are excluded.

Inclusion Criteria

Any non-target leg lesions I have can be treated before my main treatment.

Subject agrees not to participate in any other investigational device or drug study for a period of at least six months following the index procedure. Questionnaire-based studies, or other studies that are non-invasive and do not require investigational devices or medications are allowed

The blood vessels being studied are between 2.5 and 3.5 millimeters wide as measured by a special imaging test.

Exclusion Criteria

I am currently being treated for cancer or have a blood disorder.

I have severe kidney problems or am on dialysis.

I will need surgery that requires stopping blood thinners within 6 months.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive the R3 Vascular MAGNITUDE® Bioresorbable Drug-Eluting Scaffold for treating infrapopliteal artery lesions

1 day

1 visit (in-person)

Initial Follow-up

Participants are monitored for safety and effectiveness, with assessments at 30 days and 180 days post-implantation

6 months

Multiple visits (in-person and virtual)

Long-term Follow-up

Participants are monitored for long-term safety and effectiveness, with assessments up to 5 years post-implantation

5 years

Annual visits (in-person and virtual)

Treatment Details

Interventions

• MAGNITUDE® Bioresorbable Arterial Scaffold

Trial Overview The trial tests a new MAGNITUDE® Bioresorbable Drug-Eluting Scaffold designed to dissolve over time after improving blood flow in the lower leg's diseased artery. This first-in-human study aims to alleviate symptoms and reduce amputation risks by comparing it against standard care for up to three treated vascular blockages.

Participant Groups

Group I: MAGNITUDE® Scaffold Experimental Treatment 1 Intervention

Subject with up to three study lesions treated by implanting a maximum of 3 R3 Vascular MAGNITUDE® Bioresorbable Drug-Eluting Scaffolds

MAGNITUDE® Bioresorbable Arterial Scaffold is already approved in United States, Canada for the following indications:

Approved in United States as Magnitude scaffold for:

• Below-the-knee peripheral arterial disease (PAD)

Approved in Canada as Magnitude scaffold for:

• Below-the-knee peripheral arterial disease (PAD)

Who Is Running the Clinical Trial?

R3 Vascular Inc.

Lead Sponsor

Trials

3

Recruited

360+

Cardiovascular Research Foundation Clinical Trials Center

Collaborator

Trials

1

Recruited

30+

Massachusetts General Physicians Organization / Vascore

Collaborator

Trials

1

Recruited

30+

Cardiovascular Research Foundation, New York

Collaborator

Trials

28

Recruited

27,800+

VasCore Vascular Ultrasound Core Lab

Collaborator

Trials

2

Recruited

190+

Findings from Research

The new thin-walled Magnitude bioresorbable scaffold (BRS) showed significantly fewer fractures during biomechanical testing compared to the Absorb BRS, indicating better structural integrity under stress.

In a study involving 22 swine, the Magnitude-BRS demonstrated superior strut coverage and lower late recoil at 14 and 28 days, suggesting enhanced vascular healing and stability compared to the Absorb scaffold.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vitro mechanical behavior and in vivo healing response of a novel thin-strut ultrahigh molecular weight poly-l-lactic acid sirolimus-eluting bioresorbable coronary scaffold in normal swine. Cheng, Y., Gasior, P., Ramzipoor, K., et al.[2020]

In a study of 31 patients with advanced infra-popliteal peripheral arterial disease, the Absorb bioresorbable vascular scaffold demonstrated a high procedural success rate of 100% and a low rate of clinically driven target vessel failure (93.5%) at 24 months.

The scaffold showed excellent primary patency rates of 96.7% at 12 months and 87.1% at 24 months, with no observed scaffold thrombosis or peri-procedural bleeding, indicating both safety and efficacy in managing chronic limb ischemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Two-year follow-up of bioresorbable vascular scaffolds in severe infra-popliteal arterial disease. Dia, A., Venturini, JM., Kalathiya, RJ., et al.[2022]

Bioresorbable scaffolds offer a temporary support for blood vessels, gradually dissolving to reduce the risk of long-term complications associated with permanent metal implants.

These scaffolds are designed to release drugs in a controlled manner, initially providing a high concentration to prevent vascular injuries and excessive tissue growth, which can help in treating conditions like restenosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bioresorbable Scaffold-Based Controlled Drug Delivery for Restenosis. Tesfamariam, B.[2020]

A 58-year-old man with left subclavian steal syndrome was successfully treated with a bioresorbable vascular scaffold, which improved his symptoms and hemodynamics immediately after implantation.

Two years after the procedure, follow-up imaging confirmed that the treated vessel remained open, demonstrating the long-term efficacy and potential of bioresorbable scaffolds in treating vascular diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful Treatment of a Subclavian Artery Stenosis With a Coronary Bioresorbable Vascular Scaffold. Giordano, A., Messina, S., Biondi-Zoccai, G.[2022]

In a study of 31 patients with advanced infrapopliteal peripheral artery disease (PAD), the Absorb bioresorbable vascular scaffold (BVS) demonstrated a high primary patency rate of 96.7% and a freedom from clinically driven target vessel failure (CD-TVF) of 95.1% at 12 months, indicating its efficacy in managing complex lesions.

The Absorb BVS showed a favorable safety profile, with no instances of scaffold thrombosis or significant bleeding, and all patients remained alive at the 12-month follow-up, suggesting it is a safe option for treating chronic limb ischemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single arm retrospective study of bioresorbable vascular scaffolds to treat patients with severe infrapopliteal arterial disease. Dia, A., Venturini, JM., Kalathiya, R., et al.[2020]

The ART-BRS bioresorbable scaffold demonstrated early lumen enlargement in a porcine model, starting at 3 months and continuing up to 18 months, while the bare metal stent (BMS) showed no significant changes over time.

Complete bioresorption of the ART-BRS occurred by 24 months, with mild to moderate inflammation peaking at 6 months, indicating a favorable long-term vascular response compared to traditional stents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of a Drug-Free Early Programmed Dismantling PDLLA Bioresorbable Scaffold and a Metallic Stent in a Porcine Coronary Artery Model at 3-Year Follow-Up. Yahagi, K., Yang, Y., Torii, S., et al.[2019]

In a study of 125 patients with acute coronary syndromes, the ABSORB bioresorbable vascular scaffold demonstrated a high procedural success rate of 98.2% and a major adverse cardiac event-free survival rate of 90.7% over 4 years.

The use of a predilation-sizing-postdilation (PSP) technique significantly improved event-free survival to 95.8%, highlighting its importance in optimizing outcomes for patients receiving this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Longer Inflation Duration and Predilation-Sizing-Postdilation Improve Bioresorbable Scaffold Outcomes in a Long-term All-Comers Canadian Registry. Haddad, K., Tanguay, JF., Potter, BJ., et al.[2019]

In a study of 114 rheumatoid arthritis (RA) patients, a significant relationship was found between cumulative inflammatory burden (measured as ESR years) and arterial stiffness, indicating that higher inflammation correlates with stiffer arteries.

The analysis showed that for every 100 ESR-years increase, arterial stiffness (measured by aortic augmentation index) increased by 0.51, suggesting that managing inflammation could be important for cardiovascular health in RA patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Arterial stiffness and cumulative inflammatory burden in rheumatoid arthritis: a dose-response relationship independent of established cardiovascular risk factors. Crilly, MA., Kumar, V., Clark, HJ., et al.[2009]

The new heart-thigh pulse wave velocity (htPWV) method shows comparable results to the established carotid-femoral pulse wave velocity (cfPWV) in measuring arterial stiffness, with no significant difference in mean values between the two methods (713 ± 145 cm/s for cfPWV vs. 699 ± 150 cm/s for htPWV).

The htPWV method is advantageous for clinical use as it requires less technical skill and time, making it a promising tool for easily assessing arterial stiffness in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Heart-Thigh Cuff Pulse Wave Velocity: A Novel Nontechnical Measure of Arterial Stiffness. Fico, BG., Gourley, DD., Wooten, SV., et al.[2020]

In a study of 101 patients undergoing peritoneal dialysis, a higher neutrophil-lymphocyte ratio (NLR) was independently associated with increased arterial stiffness, as measured by brachial-ankle pulse wave velocity (baPWV).

The findings suggest that NLR could serve as a useful inflammatory marker for assessing arterial stiffness in these patients, but further research is needed to establish a causal relationship and explore potential treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neutrophil-lymphocyte ratio is associated with arterial stiffness in patients with peritoneal dialysis. Cai, K., Luo, Q., Zhu, B., et al.[2018]

In hemodialyzed patients, the pulse wave velocity ratio (PWV-ratio) is significantly higher on the side of the body where the vascular access (VA) is placed compared to the contralateral side, indicating increased arterial stiffness in that area.

The study found a strong correlation between arterial stiffness measurements (cf-PWV, cb-PWV, and PWV-ratio) on both sides of the body, suggesting that researchers should consider the specific side of measurement when evaluating PWV-ratio in future studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Central-To-Peripheral Arterial Stiffness Gradient in Hemodialyzed Patients Depends on the Location of the Upper-limb Vascular Access. Bia, D., Galli, C., Zocalo, Y., et al.[2019]

In young rheumatoid arthritis (RA) patients, the aortic augmentation index (AIx) is significantly higher compared to healthy controls, indicating increased arterial dysfunction, while carotid-radial pulse wave velocity (PWV) does not show a significant difference.

Treatment with infliximab, an anti-TNF-alpha therapy, significantly lowers PWV in RA patients, suggesting it improves arterial wall function, although it does not affect AIx, highlighting the different sensitivities of these measures in assessing arterial health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Non-invasive assessment of arterial stiffness indices by applanation tonometry and pulse wave analysis in patients with rheumatoid arthritis treated with TNF-alpha blocker remicade (infliximab). Cypiene, A., Laucevicius, A., Venalis, A., et al.[2015]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

In vitro mechanical behavior and in vivo healing response of a novel thin-strut ultrahigh molecular weight poly-l-lactic acid sirolimus-eluting bioresorbable coronary scaffold in normal swine. [2020]

2. England pubmed.ncbi.nlm.nih.gov

Two-year follow-up of bioresorbable vascular scaffolds in severe infra-popliteal arterial disease. [2022]

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

Bioresorbable Scaffold-Based Controlled Drug Delivery for Restenosis. [2020]

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

Successful Treatment of a Subclavian Artery Stenosis With a Coronary Bioresorbable Vascular Scaffold. [2022]

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

Single arm retrospective study of bioresorbable vascular scaffolds to treat patients with severe infrapopliteal arterial disease. [2020]

6. England pubmed.ncbi.nlm.nih.gov

Comparison of a Drug-Free Early Programmed Dismantling PDLLA Bioresorbable Scaffold and a Metallic Stent in a Porcine Coronary Artery Model at 3-Year Follow-Up. [2019]

7. England pubmed.ncbi.nlm.nih.gov

Longer Inflation Duration and Predilation-Sizing-Postdilation Improve Bioresorbable Scaffold Outcomes in a Long-term All-Comers Canadian Registry. [2019]

8. England pubmed.ncbi.nlm.nih.gov

Arterial stiffness and cumulative inflammatory burden in rheumatoid arthritis: a dose-response relationship independent of established cardiovascular risk factors. [2009]

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

Heart-Thigh Cuff Pulse Wave Velocity: A Novel Nontechnical Measure of Arterial Stiffness. [2020]

10. England pubmed.ncbi.nlm.nih.gov

Neutrophil-lymphocyte ratio is associated with arterial stiffness in patients with peritoneal dialysis. [2018]

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

Central-To-Peripheral Arterial Stiffness Gradient in Hemodialyzed Patients Depends on the Location of the Upper-limb Vascular Access. [2019]

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

Non-invasive assessment of arterial stiffness indices by applanation tonometry and pulse wave analysis in patients with rheumatoid arthritis treated with TNF-alpha blocker remicade (infliximab). [2015]