Balloon Lithoplasty for Preparation of Severely Calcified Coronary Lesions (BALI)

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Coronary Artery Disease; Percutaneous Coronary Intervention; Coronary Artery Calcification
• Intervention / Treatment: Device: Lithoplasty; Device: Conventional

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.

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Belgium
  • Leuven, Belgium
    • University Hospital Leuven
• Denmark
  • Aalborg, Denmark, 9100
    • Aalborg University Hospital
  • Aarhus, Denmark, 8200
    • Aarhus University Hospital Skejby
  • Copenhagen, Denmark, 2100
    • Rigshospitalet
  • Odense, Denmark, 5000
    • Odense University Hospital
  • Roskilde, Denmark, 4000
    • Zealand University Hospital, Roskilde Sygehus
  • Copenhagen
    • Gentofte, Copenhagen, Denmark, 2900
      • Gentofte University Hospital
• Estonia
  • Tallinn, Estonia
    • North-Estonia Medical Center
• Norway
  • Trondheim, Norway
    • Trondheim University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Lithoplasty lesion preparation; Balloon lithoplasty will be used as lesion preparation.	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.; Other Names: Lithotripsy; Shockwave
Active Comparator: Conventional lesion preparation; Conventional and modified balloons will be used as lesion preparation.	Device: 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.

What is the study measuring?

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
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 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
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
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

Collaborators and Investigators

• Sponsor: Herlev and Gentofte Hospital
• Collaborators: Abbott
• Investigators: Principal Investigator: Niels Thue Olsen, MD, PhD, Herlev and Gentofte Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 29, 2020
• Primary Completion (Estimated): September 1, 2025
• Study Completion (Estimated): January 1, 2027

Study Registration Dates

• First Submitted: January 28, 2020
• First Submitted That Met QC Criteria: January 30, 2020
• First Posted (Actual): February 5, 2020

Study Record Updates

• Last Update Posted (Actual): November 8, 2023
• Last Update Submitted That Met QC Criteria: November 6, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• 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: H-19051822

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data will be shared by request.
• IPD Sharing Time Frame: Within 1 year of study completion.
• IPD Sharing Access Criteria: Requests for access will be reviewed by the Steering Committee. A Data Access Agreement will be needed for access.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

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