Intravascular Identification and Drug-Eluting Balloon Treatment of Vulnerable Lipid-Rich Plaques (DEBuT-LRP)

Rationale: Two-thirds of intracoronary thrombi causing acute coronary syndrome (ACS) result from rupture of lipid-rich plaques (LRP). After treatment of the culprit lesion in ACS patients, additional LRPs are found in approximately 50% of patients. Near infrared spectroscopy (NIRS) combined with intracoronary ultrasound (IVUS) can identify these vulnerable plaques during coronary angiography (CAG) and is able to assess plaque characteristics and the lipid-core burden index in a 4mm segment (LCBImm4). It is currently unknown whether treatment of LRPs leads to plaque stabilization, potentially reducing the number of subsequent ACS. We hypothesize that LRPs can be treated with balloons coated with an antiproliferative drug (i.e. drug-eluting balloons; DEB) to deliver selective pharmacotherapeutic treatment to halt the local atherosclerotic process and subsequently reduce the risk for atherosclerotic events.

Objectives: To determine the change in plaque characteristics of non-culprit LRPs, as measured with IVUS/NIRS, after treatment with DEB in patients with ACS.

Study design: Prospective single-arm clinical trial

Study population: Patients with non-ST-elevation acute coronary syndromes

Intervention: If a LRP is detected with IVUS/NIRS, it will be treated with DEB. In case multiple LRPs are detected, only one will be treated.

Main study endpoints: The difference in LCBImm4 between baseline and 9 months of plaques treated with DEB.

Study Overview

• Status: Recruiting
• Conditions: Coronary Artery Disease
• Intervention / Treatment: Device: Drug-eluting balloon treatment

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jose Henriques; Phone Number: +31205669111; Email: j.p.henriques@amsterdamumc.nl
• Study Contact Backup: Name: Anna van Veelen; Email: a.vanveelen@amsterdamumc.nl

Study Locations

• Netherlands
  • Amsterdam, Netherlands, 1105AZ
    • Recruiting
    • Amsterdam UMC, location AMC
    • Contact: Jose Henriques; Email: j.p.henriques@amsterdamumc.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patient has an acute coronary syndrome without ST-segment elevation on the ECG (NSTE-ACS), including non-ST-elevation myocardial infarction and unstable angina pectoris, defined according to the Fourth Universal Definition of Myocardial Infarction.
• An invasive revascularization strategy for NSTE-ACS with PCI is chosen.

Exclusion Criteria:

- Angiographic exclusion criteria:

1. Previous coronary artery bypass-grafting;
2. Presence of a chronic total occlusion;
3. Too many (complex) coronary lesions requiring staged PCI procedure(s);

4. Procedural complication of the index PCI;

   - Clinical exclusion criteria:

5. Unstable patients (the presence of cardiogenic shock, need for intubation, need for inotropes);
6. Patients with ST-segment elevations on the ECG requiring immediate primary PCI;
7. Body weight > 250 kg;
8. Known renal insufficiency (estimated Glomerular Filtration Rate [eGFR] <30 mL/min/1.73m2 or subject on dialysis);
9. Hypersensitivity or allergy to contrast with inability to properly pre-hydrate;
10. Presence of a comorbid condition with a life expectancy of less than one year;
11. Participation in another trial;
12. Subject is belonging to a vulnerable population (per investigator's judgment, e.g., subordinate hospital staff) or is unable to read or write.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Drug-eluting balloon treatment; Drug-eluting balloon (DEB) treatment of lipid-rich plaque	Device: Drug-eluting balloon treatment; Drug-eluting balloon (DEB) treatment of lipid-rich plaque

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
LCBImm4 difference of DEB-treated LRPs	The difference in LCBImm4 between baseline and 9 months follow-up of lipid-rich plaques treated with drug-eluting balloon, as measured with near-infrared spectroscopy (NIRS).	9 months

Secondary Outcome Measures

Outcome Measure	Time Frame
The change in lipid-core burden index in a 4 mm segment (LCBImm4) as measured with IVUS + NIRS from baseline to 9 month follow-up in identified additional LRPs that are not treated with DEB.	9 months
Rate of flow-limiting dissections necessitating bail-out stent implantation;	9 months
Rate of periprocedural myocardial infarction;	9 months
Rate of LRP lesion failure (defined as cardiac death, myocardial infarction, or ischemia-driven revascularization related to an identified non-culprit LRP lesion up to one-year follow-up);	1 year
Patient-oriented composite outcomes, defined as all-cause mortality, myocardial infarction, or any repeat revascularization up to one-year follow-up;	1 year
Additional IVUS + NIRS lesion characteristics: plaque volume	9 months
Additional IVUS + NIRS lesion characteristics: minimal lumen area	9 months

Collaborators and Investigators

• Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Study record dates

Study Major Dates

• Study Start (Actual): January 19, 2021
• Primary Completion (Anticipated): December 1, 2022
• Study Completion (Anticipated): June 1, 2023

Study Registration Dates

• First Submitted: February 18, 2021
• First Submitted That Met QC Criteria: February 22, 2021
• First Posted (Actual): February 23, 2021

Study Record Updates

• Last Update Posted (Actual): February 15, 2022
• Last Update Submitted That Met QC Criteria: February 14, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: Near-infrared spectroscopy; Drug-eluting balloon; Lipid-rich plaque; Non-ST-elevation myocardial infarction
• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Disease; Coronary Artery Disease
• Other Study ID Numbers: DEBuT-LRP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes