Drug-Eluting Balloon Treatment vs. Guideline-Directed Medical Therapy for the Treatment of Lipid-Rich Plaques

Not Applicable

Not yet recruiting

• Conditions: Coronary Artery Disease; Atheroscleroses; Cardiovascular Disease; Vulnerable Coronary Plaques; Vulnerable Plaque; Lipid-Rich Atherosclerosis of Coronary Artery; Acute Coronary Syndromes (ACS)

• Registration Number: NCT07107971
• Lead Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Brief Summary

The goal of this clinical trial is to find out whether treating vulnerable plaques in the coronary arteries with a drug-coated balloon can make them less dangerous than using standard medication alone. The study includes adults with acute coronary syndrome (a type of heart problem caused by reduced blood flow in the coronary arteries).

The main questions the study aims to answer are:

* Does the drug-coated balloon reduce the amount of fat inside the plaque more than medication alone?

* Is this treatment safe for patients?

Participants will:

* Undergo imaging of their coronary arteries during their planned heart procedure (PCI)

* Be randomly assigned to receive either a drug-coated balloon treatment or no extra treatment

* Undergo a second imaging procedure 9 months later to check changes in the plaque

Detailed Description

Rationale:

Acute coronary syndromes (ACS) are often caused by rupture or erosion of certain high-risk vulnerable plaques. These plaques demonstrate specific features, such as a large lipid-rich necrotic core, a thin fibrous cap, and inflammation. Half of patients presenting with non-ST-segment elevation ACS have an additional vulnerable plaque, which increases their risk for non-culprit events during follow-up. Coronary intravascular ultrasound (IVUS) with the addition of near-infrared spectroscopy (NIRS) enables the identification of coronary lesions with high lipid content, quantified using the lipid-core burden index (LCBI) and is therefore able to distinguish plaques at risk to cause future non-culprit events. The question remains whether local and systemic treatment of such high-risk plaques decreases the risk for adverse clinical outcome.

In our previous pilot study, DEBuT-LRP, we demonstrated that it was safe and feasible to treat vulnerable lipid-rich plaques with a drug-coated balloon (DCB) and that it was able to reduce the maximum LCBI on a 4 mm segment (maxLCBI4mm) after 9 months. In this randomized controlled trial, we intend to investigate the impact of DCB treatment on the maxLCBI4mm of lipid-rich plaques when compared to guideline-directed medical therapy alone.

Objective:

To test the hypothesis that paclitaxel-coated balloon treatment of non-obstructive non-culprit vulnerable lipid-rich plaques (LRP) leads to a greater reduction of the lipid-core burden index than guideline-directed medical therapy alone.

Study design:

A prospective two-arm randomized controlled trial.

Study population:

Patients older than 18 years with ACS who are scheduled for invasive percutaneous coronary intervention (PCI) of a native coronary artery.

Intervention:

DCB treatment of LRP in addition to guideline-directed medical therapy (GDMT).

Main study parameters:

The main study endpoint is the difference in maxLCBI4mm reduction from baseline to 9 months follow-up compared between the two randomization groups.

Secondary study endpoints are clinical safety endpoints (1. Flow-limiting dissection related to DCB-treatment necessitating bail-out stenting; 2. Periprocedural myocardial infarction; 3. Bleeding; 4. LRP lesion failure: cardiovascular death, myocardial infarction or repeat revascularization related to the index LRP, 5. Patient-oriented outcome: all-cause death, myocardial infarction or repeat revascularization) and imaging endpoints (1. IVUS-derived parameters; 2. QCA endpoints and 3. NIRS analyses of non-treated vessels).

Study Timeline

• Study First Submitted: 2025-07-28
• Status Verified: 2025-08
• Study Start: 2025-08-01
• Study First Submitted QC: 2025-08-04
• Last Update Submitted: 2025-08-04
• Study First Posted: 2025-08-06
• Last Update Posted: 2025-08-06
• Primary Completion: 2028-01
• Study Completion: 2033-01-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 400

Inclusion Criteria

• Presenting with acute coronary syndrome (ACS);
• Successful PCI of a native coronary artery or major side branch;
• At least 2 native coronary arteries are accessible for invasive coronary imaging; i.e. not totally occluded and >2 mm and <6 mm reference vessel diameter.

Exclusion Criteria

• Hemodynamically unstable (presence of cardiogenic shock, need for intubation, need for inotropes);
• Known hypersensitivity to paclitaxel;
• Procedural complications of the index PCI;
• Known renal insufficiency, i.e. eGFR <30 mL/min/1.73 m2;
• Hypersensitivity or allergy to contrast with inability to administer steroid and antihistamine premedication;
• Presence of a comorbid condition with a life expectancy of less than one year;
• Body weight >250 kg;
• Subject belonging to a vulnerable population (per investigator's judgment, e.g., subordinate hospital staff) or is unable to read or write.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Difference in maxLCBI4mm of the target LRP	From baseline to 9 month follow-up.	The mean difference in maxLCBI4mm of the target LRP between baseline and 9 month follow-up compared between the two randomization groups.

Secondary Outcome Measures

Name	Time	Method
Difference in maxLCBI4mm in non-treated LRPs	From baseline to 9 month follow-up.	The change in maxLCBI4mm as measured with IVUS/NIRS from baseline to 9 month follow-up in identified additional LRPs that are not treated with DCB.
The change in IVUS- and angiography-derived measurements	From baseline to 9 month follow-up.	The change in IVUS- and angiography-derived measurements (plaque burden, minimal lumen area, mean plaque area, diameter stenosis and minimal lumen diameter) between baseline and 9 month follow-up.
Flow-limiting dissection necessitating bail-out stent implantation	From baseline to 9 month follow-up.	Flow-limiting dissection necessitating bail-out stent implantation.
Periprocedural myocardial infarction	From baseline to 9 month follow-up.	Procedure-related myocardial infarction is defined according to the Fourth Universal Definition for Myocardial Infarction. Periprocedural myocardial infarction has occurred when an elevation of cTn values \> 5 times of the 99th percentile URL in patients with normal baseline values is measured within a time window up to 48 hours post-procedure.; Patients with elevated pre-procedural cTn values, in whom the pre-procedural cTn level are stable (≤ 20% variation) or falling, must meet the criteria for a \>5 or \>10 fold increase and manifest a change from the baseline value of \>20%. In addition with at least one of the following: * New ischaemic ECG changes; * Development of new pathological Q waves; * Imaging evidence of loss of viable myocardium that is presumed to be new and in a pattern consistent with an ischaemic aetiology; * Angiographic findings consistent with a procedural flow-limiting complication.
Bleeding (BARC-3 and -5)	From baseline to 5 year follow-up.	The occurence of BARC Type 3 or 5 bleeding events.
LRP lesion failure	From baseline to 5 year follow-up.	LRP lesion failure, defined as the occurence of cardiovascular death, myocardial infarction, or ischemia-driven revascularization related to an identified non-culprit LRP lesion.
Patient-oriented composite outcome	From baseline to 5 year follow-up.	Patient-oriented composite outcome, defined as the occurrence of all-cause mortality, myocardial infarction, or any repeat revascularization.

Trial Locations

Locations (1)

Amsterdam UMC; 🇳🇱 Amsterdam, Netherlands