Paclitaxel-Coated Balloon Catheter for Stent Restenosis

(AGENT IDE Trial)

Not currently recruiting at 25 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

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

Compensation: Varies

Number of Visits: 1

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a special balloon catheter coated with the drug paclitaxel for individuals with in-stent restenosis, where a blockage has returned in a coronary artery previously treated with a stent. The trial aims to determine if this new balloon can safely and effectively clear the blockage. Individuals who previously had a stent placed in a heart artery and now face a new blockage might be suitable candidates for this trial. As a Phase 3 trial, this treatment is in the final step before FDA approval, offering participants the opportunity to contribute to a potentially groundbreaking therapy.

Do I need to stop taking my current medications for this trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you should discuss your current medications with the trial team, especially if you have allergies or intolerances to antiplatelet drugs, anticoagulants, or contrast dye.

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 should not have an intolerance to antiplatelet drugs or anticoagulants, as these are required for the procedure.

What prior data suggests that the Agent Paclitaxel Coated PTCA Balloon Catheter is safe for treating in-stent restenosis?

Research has shown that the Agent Paclitaxel Coated PTCA Balloon Catheter is safe to use. Previous studies compared it to regular balloon angioplasty and found it effectively reduces issues at the treatment site. Another study indicated that it is safe and effective for patients with small blood vessels and for those whose stents have narrowed again after placement. This treatment uses a balloon catheter coated with paclitaxel, a drug that helps prevent the artery from narrowing again.

So far, studies have shown that the Agent DCB is well-tolerated, with no major safety issues reported. This suggests it is a safe option for patients whose arteries have narrowed again after previous treatment. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about the Paclitaxel-Coated Balloon Catheter because it offers a novel approach to treating stent restenosis. While traditional treatments often involve plain balloon angioplasty or additional stenting, this catheter is unique because it delivers paclitaxel directly to the artery wall via a drug-coated balloon. Paclitaxel is known for its ability to prevent the re-narrowing of arteries by inhibiting cell growth. Additionally, this method uses a semi-compliant balloon coated with a combination of paclitaxel and an excipient, which helps in the effective delivery of the drug to the targeted site. This innovative delivery mechanism could potentially reduce the recurrence of restenosis more effectively than existing treatments.

What evidence suggests that the Agent Paclitaxel Coated PTCA Balloon Catheter is effective for in-stent restenosis?

Studies have shown that the Agent Paclitaxel Coated PTCA Balloon Catheter, which participants in this trial may receive, effectively treats in-stent restenosis (ISR), a condition where a stent in a heart artery narrows again. Research indicates that this treatment surpasses regular balloon angioplasty in reducing the likelihood of the artery narrowing again. Specifically, it lowers the rate of target lesion failure, meaning the original problem area is less likely to cause issues after treatment. Compared to uncoated balloons, paclitaxel-coated balloons like the Agent DCB effectively manage coronary ISR, helping ensure that blood flows more freely through the artery. ^{1 2 4 6 7}

Who Is on the Research Team?

Robert Yeh, MD

Principal Investigator

Beth Israel Deaconess Medical Center

Are You a Good Fit for This Trial?

This trial is for patients who have had a previous stent placed in their heart's arteries and are now experiencing re-narrowing within the same spot. The affected artery must be between 2.0 mm to 4.0 mm wide, and the blockage up to 36 mm long.

Inclusion Criteria

My heart's artery blockage is more than 50% but not completely blocked.

My target lesion has been successfully pre-dilated.

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

Exclusion Criteria

I am not pregnant or nursing.

I do not have a serious illness that could shorten my life to under 2 years.

Subject has current problems with substance abuse (e.g. alcohol, cocaine, heroin, etc.)

Timeline for a Trial Participant

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 for in-stent restenosis

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Regular visits as per protocol

What Are the Treatments Tested in This Trial?

Interventions

• Agent Paclitaxel Coated PTCA Balloon Catheter

Trial Overview The study is testing a special drug-coated balloon catheter called AGENT DCB 40 mm, designed to treat narrowed areas inside previously placed stents in heart arteries without needing another stent.

How Is the Trial Designed?

Group I: AGENT DCB 40 mm Experimental Treatment 1 Intervention

Agent DCB 40 mm 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).

Agent Paclitaxel Coated PTCA Balloon Catheter is already approved in United States for the following indications:

Approved in United States as Agent DCB for:

• Treatment of in-stent restenosis (ISR) in native coronary arteries

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

Published Research Related to This Trial

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]

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]

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]

In a study involving 14 patients undergoing peripheral angioplasty with paclitaxel-coated balloons, the procedure was successful and showed no systemic side effects from the drug, as paclitaxel plasma levels remained below harmful thresholds.

Paclitaxel levels peaked at 40 ng/ml immediately after the procedure but dropped to undetectable levels within 24 hours, indicating that the use of these coated balloons is safe and effective for preventing restenosis without significant systemic exposure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Plasma levels following application of paclitaxel-coated balloon catheters in patients with stenotic or occluded femoropopliteal arteries. Freyhardt, P., Zeller, T., Kröncke, TJ., et al.[2015]

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 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]

Citations

1. accessdata.fda.gov accessdata.fda.gov/cdrh_docs/pdf23/P230035B.pdf

SUMMARY OF SAFETY AND EFFECTIVENESS DATA (SSED) The AGENT™ Paclitaxel-Coated Balloon Catheter is intended to be used after appropriate vessel preparation in adult patients undergoing ...

2. acc.org acc.org/Latest-in-Cardiology/Clinical-Trials/2023/10/24/14/45/agent-ide

A Clinical Trial to Assess the Agent Paclitaxel Coated ... The results of this trial indicate that the Agent DCB is superior to conventional balloon angioplasty in reducing target lesion failure at 12 ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40803784/

Paclitaxel-Coated Balloon for the Treatment of Multilayer In ... Patients with ISR of multiple stent layers had higher rates of adverse stent-related events compared with patients with single-layer ISR.

4. jamanetwork.com jamanetwork.com/journals/jama/fullarticle/2816073

Paclitaxel-Coated Balloon vs Uncoated ... Treatment with a paclitaxel-coated balloon offers an effective treatment strategy for the management of coronary in-stent restenosis.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04647253

A Clinical Trial to Assess the Agent Paclitaxel Coated ... 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) ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37642826/

One-year safety and effectiveness of the Agent paclitaxel ... These data support the safety and effectiveness of the Agent paclitaxel-coated balloon in patients with small vessels and ISR.

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0735109725067786

Paclitaxel-Coated Balloon for the Treatment of Multilayer In ... We evaluated the efficacy and safety of a low-dose paclitaxel-coated vs uncoated balloon among patients with multilayer or single-layer ISR in ...