Clinical trial NCT04253171: Balloon Lithoplasty for Preparation of Severely Calcified Coronary Lesions
Official title: Balloon Lithoplasty for Preparation of Severely Calcified Coronary Lesions Before Stent Implantation - a Nationwide Randomized Trial (BALI)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Percutaneous Coronary Intervention
Coronary Artery Calcification
Coronary Artery Disease
Lead sponsor: Herlev and Gentofte Hospital
Sponsor class: OTHER
Collaborators: name: Abbott
name: Shockwave Medical, Inc.
First posted: 2020-02-05
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Investigator-initiated 1:1 randomized, controlled, multinational, superiority trial.
Primary purpose: TREATMENT

Brief summary: Severely calcified coronary stenoses are difficult to treat with percutaneous coronary intervention (PCI) using current techniques and there is little specific evidence on how to best treat these cases. It is hypothesized that balloon lithoplasty is superior to conventional balloons for lesion preparation of severely calcified coronary lesions before stent implantation in terms of procedural failure and 1-year target vessel failure.

Detailed description: Severely calcified coronary stenoses are difficult to treat with percutaneous coronary intervention (PCI) using current techniques. Severe calcifications make it difficult to sufficiently prepare lesions before stenting, to advance stents, and to achieve full stent expansion. There is increased risk of vessel dissection and perforation with angioplasty on severely calcified lesions, and long-term outcomes of PCI are adversely affected. Because severely calcified lesions are often excluded from interventional studies, there is little specific evidence on how to best treat these cases. Only a few randomized studies have specifically explored this question, focusing on the use of rotational atherectomy

Recently, the technique of balloon-based lithoplasty was made commercially available. With this technique, calcifications are cracked with the creation of high-frequency pressure oscillations in a special angioplasty balloon. Standard techniques are used to deliver and dilate the balloon. The method was developed for treatment of otherwise non-dilatable lesions, and first reported results have been encouraging. The lithoplasty device used in the current study (Shockwave IVL, Shockwave Medical, CA, USA) has received CE-mark and post-approval safety has recently been confirmed for treatment of severely calcified coronary lesions in patients.

Besides obvious benefits in non-dilatable lesions for which interventional cardiologists have few other options, it is possible this technique could change the way all severely calcified lesions are treated. Balloon lithoplasty could theoretically crack plates of calcium in the vessel wall in an orderly fashion, which could lead to safer and quicker preparation of severely calcified lesions. Furthermore, a better softening of vessel wall calcium could allow full and symmetric expansion of coronary stents, which could lead to better long-term stent patency.

Eligibility criteria: Inclusion Criteria:

* Age ≥ 18 years and \< 90 years
* Stable coronary heart disease or non-ST elevation acute coronary syndrome
* PCI planned in severely calcified, non-occluded, de-novo lesion in native vessel. Definition of severe calcifications (minimum 1 of 3 (i-iii)); i. Angiography: Radioopacities of the vessel wall visible on cine images before contrast injection on both sides of the vessel lumen in more than one projection. ii. OCT (before lesion preparation): Maximum calcium 1) angle \>180 degrees AND 2) thickness 0.5mm, AND 3) longitudinal length \>5m m. iii. IVUS (before lesion preparation): Maximum calcium angle \>270 degrees.
* Functional evidence of ischemia (non-invasive stress test or fractional flow reserve) in the target vessel territory or stenosis ≥ 90% by visual estimate
* Target vessel reference diameter visually estimated at 2.5-4 mm with ability to pass a 0.014" guidewire across lesion
* Ability to tolerate dual antiplatelet therapy
* Informed consent

Angiographic exclusion criteria:

* Unprotected left main stenosis
* Chronic total occlusion
* Severely calcified bifurcated lesion with expected need to use two stent technique
* Coronary artery dissection

Clinical exclusion criteria

* ST-segment elevation acute myocardial infarction
* Planned later revascularization in non-study lesions
* Planned cardiovascular intervention within 30 days after study intervention
* Clinical instability including decompensated heart disease
* Life expectancy of less than 1 year
* Active peptid ulcer or upper gastrointestinal bleeding within 6 months
* Ongoing systemic infection

Paraclinical exclusion criteria

* Left ventricular ejection fraction \<35 %
* Renal function with eGFR \<30 mL/min
* Pregnant or nursing

Primary outcomes:
measure: Number of patients with combined outcome of strategy failure
timeFrame: 1 year
Secondary outcomes:
measure: Number of patients with composite and components of in-hospital major adverse cardiac events (MACE)
timeFrame: In-hospital
measure: Number of patients with composite and components of major adverse cardiac events (MACE)
timeFrame: 1 year
measure: Number of patients with in-hospital procedure-related adverse events
timeFrame: In-hospital
measure: Number of patients with components of the primary outcome
timeFrame: 1 year
measure: Number of patients with components of target vessel failure
timeFrame: 1 year
measure: OCT outcomes at index procedure
timeFrame: During procedure
measure: OCT outcomes at 1 year procedure
timeFrame: 1 year
Other outcomes:
Locations:
city: Leuven
country: Belgium
facility: University Hospital Leuven
city: Gentofte
country: Denmark
facility: Gentofte University Hospital
state: Copenhagen
city: Aalborg
country: Denmark
facility: Aalborg University Hospital
city: Aarhus
country: Denmark
facility: Aarhus University Hospital Skejby
city: Copenhagen
country: Denmark
facility: Rigshospitalet
city: Odense
country: Denmark
facility: Odense University Hospital
city: Roskilde
country: Denmark
facility: Zealand University Hospital, Roskilde Sygehus
city: Tallinn
country: Estonia
facility: North-Estonia Medical Center
city: Trondheim
country: Norway
facility: Trondheim University Hospital
Study officials:
affiliation: Herlev and Gentofte Hospital
name: Niels Thue Olsen, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: