Intravascular Lithotripsy Versus Rotational Atherectomy for Severe Coronary Artery Calcification: A Prospective, Multicenter, Non-inferiority Randomized Controlled Trial

Overview

Severely calcified coronary lesions represent one of the major challenges in interventional cardiology. Severe coronary calcification increases the difficulty and complexity of percutaneous coronary intervention (PCI), impedes device delivery, and may even lead to device failure. Moreover, stent underexpansion further elevates the risks of cardiac death, myocardial infarction, target vessel revascularization, and in-stent thrombosis. Rotational atherectomy (RA) is an effective modality for treating severely calcified coronary lesions, as it adequately modifies calcific plaques, facilitates luminal enlargement, and improves device deliverability. However, RA fragments calcific plaques into microparticles that are subsequently cleared by the reticuloendothelial system in the distal microvasculature, potentially inducing microvascular dysfunction. In recent years, intravascular lithotripsy (IVL) has emerged as an innovative calcium-modification technique in clinical practice. This technology employs acoustic pressure waves to selectively disrupt deep-seated calcific plaques, inducing fractures within the calcium while sparing the soft tissue of the vessel wall from substantial injury. IVL is performed with low-pressure balloon inflation (4-6 atm), which helps to minimize the risk of vascular injury; its mechanism of action does not produce macroscopic debris, theoretically obviating distal embolization and associated microcirculatory disturbances. Recently published prospective observational studies-the REPLICA-EPIC18 and BENELUX-IVL registries-have demonstrated that IVL is feasible and safe in "real-world" severely calcified lesions, effectively facilitating stent implantation. Although both RA and IVL are important tools for managing severe calcific lesions, there remains a paucity of high-level, head-to-head evidence directly comparing post-procedural minimal stent area between the two modalities. Clarifying this issue is of significant clinical importance for guiding clinicians in selecting optimal revascularization strategies tailored to distinct pathological characteristics and patient profiles, thereby improving procedural safety and patient outcomes. To this end, we plan to conduct a prospective, multicenter, randomized clinical trial (RCT) aimed at comparing the minimal stent area between intravascular lithotripsy and rotational atherectomy in patients with severely calcified lesions.

Interventions

• Procedure intravascular lithotripsy
  The procedure entails the use of a lithotripsy balloon for dilation of severely calcified plaques. Pre-dilatation may be performed with a balloon up to 2.0 mm in diameter. Intravascular ultrasound (IVUS) with automated pullback is mandatory immediately following lithotripsy and upon completion of the procedur
• Procedure rotational atherectomy
  The procedure involves using a rotational atherectomy burr to modify severely calcified plaques. After the burr has traversed the lesion, three to five additional polishing runs are required to achieve optimal plaque modification. If 1:1 balloon dilatation at the target lesion is performed with satisfactory expansion, rotational atherectomy is terminated. Intravascular ultrasound (IVUS) with automatic pullback must be performed both immediately after rotational atherectomy and at the end of the

Primary outcome measures

• minimal stent area [Time frame: Within one hour post-percutaneous coronary intervention]

Eligibility criteria

Inclusion criteria

• Age ≥ 18 years;
• Target lesion with diameter stenosis ≥ 50% (visual estimation) associated with evidence of myocardial ischemia;
• Target lesion must be a de novo, in-situ severely calcified coronary lesion, where severe calcification is defined as: radiopacity visible prior to contrast injection and in the absence of cardiac pulsation, typically involving both sides of the vessel wall; and ≥270° circumferential calcification as evidenced by intravascular ultrasound (IVUS);
• Target vessel reference diameter between 2.5 and 4.0 mm, with successful guidewire traversal;
• A maximum of two non-target lesions requiring interventional treatment, which must be successfully treated prior to the target lesion;
• Patients presenting with evidence of symptomatic or asymptomatic myocardial ischemia, stable or unstable angina pectoris, or prior myocardial infarction;
• Signed written informed consent obtained.

Exclusion criteria

• Cardiogenic shock or hemodynamic instability;
• Chronic total occlusion (CTO);
• Requirement for intraprocedural mechanical circulatory support, such as intra-aortic balloon pump (IABP) or Impella device;
• Acute ST-segment elevation myocardial infarction (STEMI) occurring within 1 month prior to enrollment;
• Angiographically visible thrombus at the target lesion site;
• Left main ostial lesion with stenosis ≥ 50%;
• Left ventricular ejection fraction (LVEF) < 40%;
• New-onset stroke or transient ischemic attack (TIA) within 90 days;
• Bypass graft lesion;
• Coronary artery dissection of type B or greater (NHLBI classification);
• Pregnant or lactating patients;
• Life expectancy < 1 year;
• Active bleeding;
• Renal insufficiency, defined as estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m²;
• Presence of cognitive or psychiatric disorders, as confirmed by clinical diagnosis or investigator assessment;
• Illiteracy, semi-literacy, or any visual impairment, reading/writing disability that prevents the patient from independently reading the patient information sheet and personally providing written informed consent without assistance.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07750964 · 2026-0688

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗