Balloon Lithoplasty for Preparation of Severely Calcified Coronary Lesions

Coronary Artery Disease Clinical Trial

— BALI  

Official title:

Balloon Lithoplasty for Preparation of Severely Calcified Coronary Lesions Before Stent Implantation - a Nationwide Randomized Trial (BALI)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04253171
• Other study ID #: H-19051822
• Status: Active, not recruiting
• Phase: N/A
• Start date: January 29, 2020
• Est. completion date: January 1, 2027

Study information

• Verified date: November 2023
• Source: Herlev and Gentofte Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 200
• Est. completion date: January 1, 2027
• Est. primary completion date: September 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

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

Related Conditions & MeSH terms

• Coronary Artery Calcification
• Coronary Artery Disease
• Percutaneous Coronary Intervention

Intervention

Device:
• Lithoplasty
The lithoplasty balloon should be utilized as early as possible. If it is necessary for passage of the lithoplasty balloon, the lesion may first be predilated with an undersized conventional balloon, non-compliant or semi-compliant. If passage of the lithoplasty balloon is still not possible, it is recommended to perform rotational atherectomy with a small burr size. The lithoplasty balloon is sized 1:1 to reference diameter. Lithoplasty is performed with the balloon dilated at 4 atmospheres, and 10 shocks are delivered, after which the balloon is expanded to 6 atmospheres for 30 seconds, and then deflated. Up to 8 series of balloon expansion/deflation can be delivered in this manner if necessary, and several balloons may be used for long lesions.
• Conventional
Lesion preparation is performed starting with conventional balloons, non-compliant or semi-compliant. Unless fully satisfactory dilatation is achieved with conventional balloons, it is recommended to also use modified balloons (scoring balloons, cutting balloons). If balloons cannot be passed or if dilatation is inadequate, the lesion may first be predilated with an undersized conventional, non-compliant, or semi-compliant balloon. If necessary, rotational atherectomy with a small burr size can be used to facilitate adequate balloon preparation.

Locations

Country	Name	City	State
Belgium	University Hospital Leuven	Leuven
Denmark	Aalborg University Hospital	Aalborg
Denmark	Aarhus University Hospital Skejby	Aarhus
Denmark	Rigshospitalet	Copenhagen
Denmark	Gentofte University Hospital	Gentofte	Copenhagen
Denmark	Odense University Hospital	Odense
Denmark	Zealand University Hospital, Roskilde Sygehus	Roskilde
Estonia	North-Estonia Medical Center	Tallinn
Norway	Trondheim University Hospital	Trondheim

Sponsors (2)

Lead Sponsor	Collaborator
Herlev and Gentofte Hospital	Abbott

Countries where clinical trial is conducted

Belgium,  Denmark,  Estonia,  Norway, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of patients with combined outcome of strategy failure	Failed stent delivery, residual area stenosis = 20% (OCT-assessed) after PCI, or target vessel failure.; Residual area stenosis will be defined as [minimal stent area/reference area]. The reference area will be calculated by averaging the proximal and distal reference areas, which will be determined by measuring the lumen contours on most healthy-looking frame of the final OCT in the 0-5 mm edge segments. If a reference cannot be measured on the final OCT, it will be measured on a pre-stent OCT or by using quantitative coronary angiography if pre-stent OCT is unavailable. Target vessel failure will be defined as cardiac death, target vessel-related myocardial infarction, or clinically driven target vessel revascularization).	1 year
Secondary	Number of patients with composite and components of in-hospital major adverse cardiac events (MACE)	Cardiac death, Any myocardial infarction, Stroke	In-hospital during and immediately after procedure
Secondary	Number of patients with in-hospital procedure-related adverse events	Periprocedural myocardial infarction, Coronary dissection (beyond intended by lesion preparation), Coronary perforation/rupture, Coronary abrupt closure, Coronary low flow/no flow, Arrhythmia	In-hospital during and immediately after procedure
Secondary	Number of patients with components of target vessel failure	Cardiac death, Target vessel-related myocardial infarction, Clinically driven target vessel revascularization	1 year
Secondary	Number of patients with components of the primary outcome	Failed stent delivery, Residual area stenosis >20% (OCT-assessed) after PCI, Target vessel failure	1 year
Secondary	OCT outcomes at index procedure	Core-lab quantification of: Stent expansion, Stent malapposition, Quantified evidence of calcium disruption	During procedure
Secondary	OCT outcomes at 1 year procedure	Core-lab quantification of: In-stent late lumen loss, In-segment late lumen loss, In-segment re-stenosis, Stent malapposition, Quantified evidence of calcium disruption,	1 year
Secondary	Number of patients with composite and components of major adverse cardiac events (MACE)	Cardiac death, Any myocardial infarction, Stroke	1 year
Secondary	Number of patients with primary endpoint and its composites at 2 years	Failed stent delivery, residual area stenosis = 20% (OCT-assessed) after PCI, or target vessel failure	2 years
Secondary	Number of patients with composite of target vessel failure and its components at 2 years	Cardiac death, Target vessel-related myocardial infarction, Clinically driven target vessel revascularization	2 years
Secondary	Overall mortality at 1 year	Death due to any cause	1 year
Secondary	Overall mortality at 2 years	Death due to any cause	2 years