Balloon Lithoplasty for Preparation of Severely Calcified Coronary Lesions

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Percutaneous Coronary Intervention, Coronary Artery Calcification, Coronary Artery Disease

Intervention / Treatment
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* Device: Lithoplasty
* Device: Conventional


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Investigator-initiated 1:1 randomized, controlled, unblinded, nationwide, superiority trial.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Lithoplasty lesion preparation<br>Balloon lithoplasty will be used as lesion preparation. | Device: Lithoplasty<br>* 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.<br>* Other names: Lithotripsy;|
| Active Comparator: Conventional lesion preparation<br>Conventional and modified balloons will be used as lesion preparation. | Device: Conventional<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| Number of patients with components of target vessel failure | Cardiac death, Target vessel-related myocardial infarction, Clinically driven target vessel revascularization | 1 year | 
| 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 | 
| OCT outcomes at index procedure | Core-lab quantification of: Stent expansion, Stent malapposition, Quantified evidence of calcium disruption | During procedure | 
| 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 | 
| Number of patients with composite and components of major adverse cardiac events (MACE) | Cardiac death, Any myocardial infarction, Stroke | 1 year | 
| 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 | 
| 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 | 
| Overall mortality at 1 year | Death due to any cause | 1 year | 
| Overall mortality at 2 years | Death due to any cause | 2 years |