Paclitaxel Coated Balloon for Stent Restenosis

(AGENT IDE Trial)

Recruiting at 39 trial locations

Overseen By Patricia O'Mara

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Boston Scientific Corporation

Must not be taking: Antiplatelets, Anticoagulants

Disqualifiers: Cancer, Heart failure, Substance abuse, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

Duration: 1 day

600 Participants Needed

Trial Summary

What is the purpose of this trial?

AGENT IDE is a Prospective, Randomized (2:1), Multicenter Trial. The purpose of this study is to assess the safety and effectiveness of the Agent Paclitaxel Coated PTCA Balloon Catheter compared to balloon angioplasty (POBA) in patients with in-stent restenosis (ISR) of a previously treated lesion of up to 26 mm in length (by visual estimate) in a native coronary artery 2.0 mm to 4.0 mm in diameter.

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 an intolerance to antiplatelet drugs or anticoagulants, you may not be eligible to participate.

What data supports the effectiveness of the drug-coated balloon treatment for stent restenosis?

Research shows that paclitaxel-coated balloons can help reduce the risk of restenosis (re-narrowing of blood vessels) after procedures like angioplasty, especially in conditions like femoropopliteal artery disease. However, their effectiveness for drug-eluting stent restenosis in coronary arteries is less clear, with some studies indicating limited benefits. ^{1 2 3 4 5}

Is the Paclitaxel Coated Balloon generally safe for humans?

The safety of the Paclitaxel Coated Balloon, including the AGENT DCB, has been studied in various conditions. Some studies suggest it is safe for use in treating coronary and femoropopliteal artery diseases, but there is conflicting evidence about the risk of mortality, indicating the need for careful consideration and consultation with a healthcare provider. ^{1 3 6 7 8}

How is the Agent DCB drug different from other treatments for stent restenosis?

The Agent DCB is unique because it uses a paclitaxel coating to deliver the drug directly to the vessel wall, which may help prevent the narrowing of the artery after a stent is placed. This method is different from traditional treatments as it combines the mechanical action of a balloon with the targeted drug delivery, potentially reducing the risk of restenosis (re-narrowing of the artery). ^{3 4 6 7 9}

Research Team

Robert Yeh, MD

Principal Investigator

Beth Israel Deaconess Medical Center

Eligibility Criteria

This trial is for adults with in-stent restenosis, a condition where arteries narrow after stent placement. Participants must have a lesion treatable by one balloon and agree to contraception if applicable. Exclusions include recent heart procedures, severe heart or kidney issues, COVID-19 within 4 weeks, pregnancy, certain blood disorders, drug abuse, and allergies to trial materials.

Inclusion Criteria

Subject (or legal guardian) understands the trial requirements and the treatment procedures, and provides written informed consent before any trial-specific tests or procedures are performed

My target lesion is in a vein or artery graft.

My target lesion is smaller than 26 mm and can be covered by one balloon.

Exclusion Criteria

I have severe kidney problems or am on dialysis.

I had a severe heart attack less than 72 hours ago.

I have had COVID-19 recently or am currently infected but my symptoms have resolved.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive treatment with the Agent Paclitaxel Coated PTCA Balloon Catheter or balloon angioplasty (POBA) for in-stent restenosis

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Multiple visits (in-person)

Treatment Details

Interventions

• AGENT DCB
• PTCA balloon catheter

Trial Overview The study compares the Agent Paclitaxel Coated PTCA Balloon Catheter against standard balloon angioplasty for treating narrowed arteries due to previous stents. It's randomized (2:1) across multiple centers with participants having lesions up to 26 mm long in coronary arteries sized 2.0-4.0 mm.

Participant Groups

Group I: AGENT DCB Experimental Treatment 1 Intervention

Agent DCB is a Monorail Percutaneous Transluminal Coronary Angioplasty (PTCA) balloon catheter with a semi-compliant balloon coated with a formulation of paclitaxel (drug) and an excipient, Acetyl-Tri-n-butyl citrate (ATBC). The balloon catheter platform is based on the commercially available BSC Emerge™ PTCA balloon catheter system (K130391).

Group II: Commercially available, PTCA Dilation Catheter Active Control 1 Intervention

Who Is Running the Clinical Trial?

Boston Scientific Corporation

Lead Sponsor

Trials

758

Recruited

867,000+

Michael F. Mahoney

Boston Scientific Corporation

Chief Executive Officer since 2016

MBA from Wake Forest University, BBA in Finance from the University of Iowa

Kenneth Stein

Boston Scientific Corporation

Chief Medical Officer since 2020

MD from Harvard Medical School, MMSc in Clinical Investigation from Harvard-MIT Division of Health Sciences and Technology

Findings from Research

Paclitaxel-coated balloons (DCB) significantly increased the risk of needing further procedures to treat the same artery (freedom from target lesion revascularization) compared to plain old balloon angioplasty (POBA), with a risk ratio of 1.24 at 12 months and 1.39 at 24 months based on a meta-analysis of 14 studies involving 2504 patients.

There was also an increased risk of all-cause mortality at 24 months after DCB treatment, with a risk ratio of 1.53, indicating a potential safety concern, although causation was not established.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Benefit and risk from paclitaxel-coated balloon angioplasty for the treatment of femoropopliteal artery disease: A systematic review and meta-analysis of randomised controlled trials. Klumb, C., Lehmann, T., Aschenbach, R., et al.[2022]

In a study of 135 patients treated with paclitaxel drug-coated balloons (DCB) for in-stent restenosis (ISR), DCB was found to be significantly less effective for drug-eluting stent (DES) ISR compared to bare metal stent (BMS) ISR, with higher rates of binary restenosis (57% vs. 29%) and target lesion revascularization (TLR) (46% vs. 18%).

The reduced efficacy of DCB treatment was particularly notable in DES-ISR located in degenerated saphenous vein grafts (SVGs), where TLR was required in 72% of cases, compared to only 14% for BMS-ISR, highlighting the challenges of treating DES-ISR.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug Coated Balloon Is Less Effective for Treatment of DES In-Stent Restenosis Both in Native Coronary Arteries and Saphenous Vein Grafts: Results From a Bicenter Registry. Resch, M., Ostheim, P., Endemann, DH., et al.[2019]

The Agent paclitaxel-coated balloon (DCB) demonstrated a high procedural success rate of 92% and a one-year major adverse cardiac event (MACE) rate of 5.7% across 354 patients treated in a real-world registry, indicating its safety and efficacy during percutaneous coronary intervention (PCI).

While the overall MACE rate was low, patients with in-stent restenosis (ISR) experienced a higher rate of 8.3%, suggesting that this group may be at greater risk, which aligns with their more complex clinical profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Percutaneous Coronary Intervention With the Agent Paclitaxel-Coated Balloon: A Real-World Multicenter Experience. Iannopollo, G., Giannini, F., Ponticelli, F., et al.[2021]

A novel drug-coated balloon (DCB) with 6 μg of paclitaxel (Ptx) per mm² was shown to significantly increase drug concentration in the vessel wall compared to a standard DCB with 3 μg/mm², potentially enhancing its effectiveness in preventing restenosis.

Using a single balloon with 6 μg Ptx/mm² not only doubles the drug delivery compared to the 3 μg/mm² balloons but also simplifies the procedure and may lower healthcare costs by reducing the need for multiple balloons.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A novel paclitaxel coated balloon with increased drug transfer for treatment of complex vascular lesions. Gemeinhardt, O., Schnorr, B., Speck, U., et al.[2021]

In a multicenter trial involving 171 patients, the novel paclitaxel-coated drug-coated balloon (DCB) significantly reduced late lumen loss by 0.92 mm compared to uncoated balloon angioplasty (POBA) at six months, indicating better efficacy in preventing restenosis.

Patients treated with the DCB showed improved walking ability and a much lower rate of target lesion revascularization (1.3% in the DCB group vs. 18.7% in the POBA group) after 12 months, demonstrating both safety and effectiveness of the DCB in treating peripheral artery disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of a novel paclitaxel-nano-coated balloon for femoropopliteal angioplasty: one-year results of the EffPac trial. Teichgräber, U., Lehmann, T., Aschenbach, R., et al.[2020]

References

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

Drug-Coated Balloon Treatment for Femoropopliteal Artery Disease: The IN.PACT Global Study De Novo In-Stent Restenosis Imaging Cohort. [2022]

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

Paclitaxel-coated balloon for the treatment of drug-eluting stent restenosis: subanalysis results from the Valentines I trial. [2015]

3. England pubmed.ncbi.nlm.nih.gov

Benefit and risk from paclitaxel-coated balloon angioplasty for the treatment of femoropopliteal artery disease: A systematic review and meta-analysis of randomised controlled trials. [2022]

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

Drug Coated Balloon Is Less Effective for Treatment of DES In-Stent Restenosis Both in Native Coronary Arteries and Saphenous Vein Grafts: Results From a Bicenter Registry. [2019]

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

Paclitaxel exposure: Long-term safety and effectiveness of a drug-coated balloon for claudication in pooled randomized trials. [2021]

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

Percutaneous Coronary Intervention With the Agent Paclitaxel-Coated Balloon: A Real-World Multicenter Experience. [2021]

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

Rationale and design of a randomized study comparing the agent drug coated balloon to plain old balloon angioplasty in patients with In-stent restenosis. [2021]

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

A novel paclitaxel coated balloon with increased drug transfer for treatment of complex vascular lesions. [2021]

9. France pubmed.ncbi.nlm.nih.gov

Efficacy and safety of a novel paclitaxel-nano-coated balloon for femoropopliteal angioplasty: one-year results of the EffPac trial. [2020]