Sirolimus-Eluting Scaffold for Critical Limb Ischemia

Recruiting at 3 trial locations

Overseen By Jeff Anderson

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: REVA Medical, Inc.

Must not be taking: Anticoagulants, Antiplatelets

Disqualifiers: Stroke, MI, Renal failure, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: Immediate procedure

292 Participants Needed

Trial Summary

What is the purpose of this trial?

Pre-market clinical evaluation of the MOTIV Sirolimus-Eluting Bioresorbable Scaffold for the planned treatment of infrapopliteal lesions.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment for critical limb ischemia?

Research on similar bioresorbable scaffolds, like the sirolimus-eluting Fantom scaffold, shows promising mechanical performance and healing patterns, suggesting that these types of treatments can provide effective support and healing in arteries. Additionally, studies on the Absorb everolimus-eluting scaffold in arteries below the knee indicate positive midterm outcomes, which may imply potential benefits for critical limb ischemia. ^{1 2 3 4 5}

Is the Sirolimus-Eluting Scaffold generally safe for humans?

Research on sirolimus-eluting bioresorbable scaffolds, like the Magmaris and MeRes100, shows they are generally safe in humans, with studies reporting positive safety outcomes over several years. These scaffolds are designed to support blood vessels temporarily and then dissolve, reducing long-term risks associated with permanent implants. ^{6 7 8 9 10}

What makes the MOTIV Sirolimus-Eluting Bioresorbable Scaffold treatment unique for critical limb ischemia?

The MOTIV Sirolimus-Eluting Bioresorbable Scaffold is unique because it provides temporary mechanical support to the blood vessels and gradually dissolves, unlike permanent metal stents. It releases sirolimus, a drug that helps prevent the re-narrowing of blood vessels, while the scaffold itself eventually disappears, allowing the artery to heal naturally. ^{2 3 4 10 11}

Research Team

Ehrin Armstrong, MD

Principal Investigator

Adventist Health

Andrej Schmidt, MD

Principal Investigator

University Leipzig

Eligibility Criteria

Adults with symptomatic critical limb ischemia classified as Rutherford category 4 or 5 can join this trial. They must have specific artery blockages in the leg that are treatable with up to four scaffolds and agree to all study procedures. Excluded are those with severe allergies, recent major amputations, other ongoing clinical studies, certain heart conditions, untreated vessel issues, pregnancy, or a life expectancy of less than one year.

Inclusion Criteria

My target lesion is higher than 4 cm above my ankle.

My target lesion can be treated with a stent without blocking major blood vessels.

My blood vessels in the leg are open and flow well to my foot.

Exclusion Criteria

I had a major amputation less than a year ago and cannot walk on my own.

I had a stroke within the last 3 months.

Subject has severe medical comorbidities or other medical, social or psychological condition that could limit subject's ability to participate in the study or is associated with a life expectancy of less than 1 year

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either the MOTIV Sirolimus-Eluting Bioresorbable Scaffold or Percutaneous Transluminal Angioplasty (PTA) for the treatment of infrapopliteal lesions

Immediate procedure

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness, including freedom from major adverse limb events and all-cause peri-operative death

6 months

Multiple visits (in-person)

Treatment Details

Interventions

• MOTIV Sirolimus-Eluting Bioresorbable Scaffold
• Percutaneous Transluminal Angioplasty (PTA) Device

Trial Overview The MOTIV BTK Trial is testing a new type of scaffold for treating narrow blood vessels below the knee compared to standard balloon angioplasty. The scaffold releases a drug called Sirolimus and dissolves over time aiming to improve blood flow without leaving permanent material behind.

Participant Groups

Group I: MOTIV Sirolimus-Eluting Bioresorbable Scaffold Experimental Treatment 1 Intervention

Participants who receive the MOTIV device will be included in this arm

Group II: Percutaneous Transluminal Angioplasty (PTA) Active Control 1 Intervention

Participants who receive PTA treatment will be included in this arm

MOTIV Sirolimus-Eluting Bioresorbable Scaffold is already approved in United States for the following indications:

Approved in United States as MOTIV Sirolimus-Eluting Bioresorbable Scaffold for:

• Infrapopliteal lesions

Who Is Running the Clinical Trial?

REVA Medical, Inc.

Lead Sponsor

Trials

7

Recruited

2,200+

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]

The sirolimus-eluting Fantom bioresorbable scaffold (BRS) demonstrated effective healing patterns at 6 and 9 months post-implantation, with nearly complete strut coverage (98.1% at 6 months and 98.9% at 9 months) and resolution of strut malapposition.

The scaffold maintained stability throughout the follow-up period, showing no signs of late recoil, which suggests its potential for safe and effective use in patients with stable angina pectoris.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mechanical performance and healing patterns of the novel sirolimus-eluting bioresorbable Fantom scaffold: 6-month and 9-month follow-up by optical coherence tomography in the FANTOM II study. Simonsen, JK., Holck, EN., Carrié, D., et al.[2021]

Bioresorbable scaffolds (BRS) are a new type of device for treating blocked arteries that provide temporary support and drug delivery to prevent re-narrowing, functioning similarly to drug-eluting stents initially.

As BRS degrade over time, they transition from providing mechanical support to allowing the artery to regain its natural function, which may offer long-term benefits similar to traditional balloon angioplasty.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paving the way to a bioresorbable technology: Development of the absorb BRS program. Perkins, LE., Kossuth, MB., Fox, JC., et al.[2017]

In a long-term study involving 14 bioresorbable scaffolds (BRS) implanted in the iliofemoral arteries of 7 Yucatan miniswine, the sirolimus-eluting BRS demonstrated significant improvements in lumen area over time, indicating effective vessel support and remodeling.

The study showed that the BRS had minimal inflammatory reactions and nearly complete polymer degradation by 3.3 years, suggesting a favorable safety profile and potential for long-term use without the complications associated with metallic stents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term performance and biocompatibility of a novel bioresorbable scaffold for peripheral arteries: A three-year pilot study in Yucatan miniswine. Melnick, G., Ferrone, M., Cheng, Y., et al.[2020]

The everolimus-eluting bioresorbable vascular scaffold (Absorb) showed excellent midterm safety and efficacy in treating tibial and distal popliteal lesions, with a 96% primary patency rate at 12 months and 84.6% at 24 months based on a study involving 33 patients and 38 treated limbs.

Only 6% of the scaffolds experienced binary restenosis, and there were no major amputations, resulting in a 100% limb-salvage rate, indicating that this treatment is effective for patients with critical limb ischemia and severe claudication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Experience With the Absorb Everolimus-Eluting Bioresorbable Vascular Scaffold in Arteries Below the Knee: 12-Month Clinical and Imaging Outcomes. Varcoe, RL., Schouten, O., Thomas, SD., et al.[2018]

The BIOSOLVE-II and -III studies, involving 184 patients, demonstrated that a magnesium-based sirolimus-eluting bioresorbable scaffold is safe, with no cases of definite or probable scaffold thrombosis reported over a 3-year follow-up period.

At 3 years post-implantation, 91.5% of patients remained symptom-free, and the target lesion failure rate was low at 6.3%, indicating effective long-term performance of the scaffold in treating coronary artery lesions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sustained Safety and Performance of the Second-Generation Sirolimus-Eluting Absorbable Metal Scaffold: Pooled Outcomes of the BIOSOLVE-II and -III Trials at 3 Years. Haude, M., Ince, H., Kische, S., et al.[2021]

In a study involving 1,189 patients who received bioresorbable vascular scaffolds (BVS) during percutaneous coronary intervention, the target lesion failure (TLF) rate was 4.4% at six months, indicating acceptable early and midterm outcomes for this treatment.

However, the study also found that scaffold thrombosis occurred in 2.1% of patients by six months, with most cases happening within the first 30 days, highlighting a safety concern that needs to be monitored closely.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Percutaneous coronary intervention with everolimus-eluting bioresorbable vascular scaffolds in routine clinical practice: early and midterm outcomes from the European multicentre GHOST-EU registry. Capodanno, D., Gori, T., Nef, H., et al.[2022]

In a study involving 183 patients with de novo coronary artery disease, the Absorb bioresorbable vascular scaffold demonstrated a high procedural success rate of 100% and achieved significant improvements in artery diameter after treatment.

At the one-year follow-up, the safety profile was favorable, with only one death (0.5%) and a low rate of complications, including 2.8% requiring further procedures due to restenosis, indicating effective long-term outcomes in a real-world setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Beyond the early stages: insights from the ASSURE registry on bioresorbable vascular scaffolds. Wöhrle, J., Naber, C., Schmitz, T., et al.[2015]

The Magmaris sirolimus-eluting bioresorbable magnesium scaffold demonstrated a high device success rate of 97.3% and a procedure success rate of 98.9% in a large study of 1,075 patients with 1,121 lesions.

At 12 months, the target lesion failure rate was low at 4.3%, with only 0.5% of patients experiencing scaffold thrombosis, indicating a strong safety profile for the scaffold in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

BIOSOLVE-IV-registry: Safety and performance of the Magmaris scaffold: 12-month outcomes of the first cohort of 1,075 patients. Verheye, S., Wlodarczak, A., Montorsi, P., et al.[2022]

The MeRes100 bioresorbable vascular scaffold (BRS) demonstrated a safe and tolerable profile with limited systemic exposure to sirolimus, as shown in a pharmacokinetic sub-study involving 10 patients.

Sirolimus reached peak concentration in the bloodstream between 0.5 to 3 hours after implantation, with a half-life of approximately 98.6 hours, indicating effective drug release from the scaffold over time.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetic Study of Sirolimus-Eluting BioResorbable Vascular Scaffold System for Treatment of De Novo Native Coronary Lesions: A Sub-Study of MeRes-1 Trial. Chandra, P., Mahajan, AU., Bulani, VD., 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]

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

Mechanical performance and healing patterns of the novel sirolimus-eluting bioresorbable Fantom scaffold: 6-month and 9-month follow-up by optical coherence tomography in the FANTOM II study. [2021]

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

Paving the way to a bioresorbable technology: Development of the absorb BRS program. [2017]

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

Long-term performance and biocompatibility of a novel bioresorbable scaffold for peripheral arteries: A three-year pilot study in Yucatan miniswine. [2020]

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

Experience With the Absorb Everolimus-Eluting Bioresorbable Vascular Scaffold in Arteries Below the Knee: 12-Month Clinical and Imaging Outcomes. [2018]

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

Sustained Safety and Performance of the Second-Generation Sirolimus-Eluting Absorbable Metal Scaffold: Pooled Outcomes of the BIOSOLVE-II and -III Trials at 3 Years. [2021]

7. France pubmed.ncbi.nlm.nih.gov

Percutaneous coronary intervention with everolimus-eluting bioresorbable vascular scaffolds in routine clinical practice: early and midterm outcomes from the European multicentre GHOST-EU registry. [2022]

8. France pubmed.ncbi.nlm.nih.gov

Beyond the early stages: insights from the ASSURE registry on bioresorbable vascular scaffolds. [2015]

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

BIOSOLVE-IV-registry: Safety and performance of the Magmaris scaffold: 12-month outcomes of the first cohort of 1,075 patients. [2022]

10. Canada pubmed.ncbi.nlm.nih.gov

Pharmacokinetic Study of Sirolimus-Eluting BioResorbable Vascular Scaffold System for Treatment of De Novo Native Coronary Lesions: A Sub-Study of MeRes-1 Trial. [2022]

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

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