Intravascular Lithotripsy Versus Conventional Therapy for Severely Calcified Coronary Artery Lesions (REC-CHIPCAC)

Intravascular Lithotripsy Versus Conventional Therapy for Severely Calcified Coronary Artery Lesions: an Investigator-initiated, Open-label, Multicentre, Randomised, Superiority Trial

Percutaneous coronary intervention (PCI) encounters challenges with calcified coronary lesions, leading to potential issues such as failed balloon dilatation, incomplete stent expansion, and increased risks of adverse events post-PCI, including stent restenosis and thrombosis.

Intravascular lithotripsy (IVL), a novel approach for severely calcified coronary lesion preparation, has shown promising preliminary outcomes. Combining IVL with conventional approaches, such as Rotational atherectomy (RA), non-compliant balloons, or cutting balloons, may associated with additional benefit than conventional approaches only in terms of better stent expansion and lower long-term adverse events.

This pilot randomized trial aims to investigate whether combining IVL to conventional therapy surpasses the efficacy of conventional approaches alone. The primary effectiveness endpoint is final stent expansion assessed by post-procedure optical coherence tomography (OCT), and the primary safety endpoint is target lesion failure (TVF). The trial seeks to provide valuable insights into the optimal approach for managing severely calcified coronary lesions during PCI.

Study Overview

• Status: Recruiting
• Conditions: De Novo Stenosis; Severely Calcified Coronary Stenoses
• Intervention / Treatment: Procedure: Intravascular Lithotripsy; Procedure: Conventional lesion preparation strategy

• Study Type: Interventional
• Enrollment (Estimated): 220
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Ruining Zhang, BSc; Phone Number: +86-15802990370; Email: ruining-zhang@qq.com
• Study Contact Backup: Name: Chao Gao,, M.D, Ph.D; Phone Number: +86-18629551066; Email: woshigaochao@gmail.com

Study Locations

• China
  • Shannxi
    • Xi'an, Shannxi, China, 710032
      • Recruiting
      • Ling Tao
      • Contact: Chao Gao; Email: woshigaochao@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

General Inclusion Criteria:

1. Patients with acute or chronic coronary artery syndrome indicated for PCI with stenting.
2. Able to understand and provide informed consent and comply with all study procedures

Angiographic Inclusion Criteria:

1. Native and de novo coronary artery disease
2. Lesion navigable by a 0.014" guidewire.

3. Target lesion is severely calcified, meeting one of the following criteria:

   • Presence of calcium ≥ 270°, lengths ≥ 5mm, and thickness ≥ 0.5mm at one cross-section as assessed by OCT
   • If the OCT catheter is unable to pass through the target lesion after dilatation due to calcification or tortuosity, and the target lesion is severely calcified on both sides of the arterial wall during angiography, with the length of the calcification >15 mm, the lesion will be recognized as a severely calcified lesion, meeting the criteria for enrollment

Exclusion Criteria:

General Exclusion Criteria:

1. Patients under 18 years of age.
2. Incapable of providing informed consent.
3. Female patients who are pregnant or nursing (a pregnancy test must be conducted within 7 days before the index procedure for women of childbearing potential, as per local practice).
4. Concurrent medical conditions with a life expectancy of less than 1 year.
5. Hemodynamic instability.
6. Known contraindications to medications such as Heparin, anticoagulation, antiplatelet drugs, or contrast.
7. Active bleeding.
8. New-onset stroke or transient ischemic attack (TIA) within 90 days prior to enrollment.
9. Severe renal dysfunction (eGFR ≤ 30 ml/min).
10. Patients scheduled to undergo cardiac intervention or cardiac surgery within 30 days of the index procedure.
11. Recent ST-segment elevation myocardial infarction (STEMI) within 7 days or recent cardiogenic shock.
12. Lesions located in surgical conduits.

Angiographic Exclusion Criteria:

1. Target vessel exhibiting C-F type dissection.
2. Thrombosis observed by angiography or OCT.
3. Presence of an aneurysm within 10 mm of the target lesion.
4. Left main ostial lesion

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Conventional lesion preparation plus Intravascular Lithotripsy strategy; IVL could be performed before, amidst, or after Conventional lesion preparation therapy; However, the use of IVL treatment is mandatory.	Procedure: Intravascular Lithotripsy; The size of the IVL balloon catheter is selected in a 1:1 ratio to the distal reference vessel diameter. The balloon catheter is then inflated to 4 atm, and 10 impulses are delivered. Subsequently, the balloon is inflated to 8 atm and then deflated to re-establish blood flow. Up to 100 impulses can be delivered, and the balloon can be repositioned within the lesion. In cases involving multiple lesions with different reference vessel diameters, various sizes of IVL balloons may be employed. If the IVL balloon catheter is unable to pass through the lesion, pre-dilatation can be performed using a smaller diameter noncompliant balloon or rotational atherectomy.; Procedure: Conventional lesion preparation strategy; Conventional lesion preparation strategy includes the use of Compliant, noncompliant, cutting, or scoring balloons, Excimer laser coronary atherectomy, or Rotational atherectomy at the discretion of the operator.
Active Comparator: Conventional lesion preparation strategy; Conventional lesion preparation strategy includes the use of Compliant, noncompliant, cutting, or scoring balloons, Excimer laser coronary atherectomy, or Rotational atherectomy at the discretion of the operator.	Procedure: Conventional lesion preparation strategy; Conventional lesion preparation strategy includes the use of Compliant, noncompliant, cutting, or scoring balloons, Excimer laser coronary atherectomy, or Rotational atherectomy at the discretion of the operator.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Final stent expansion (%) assessed by OCT	The primary efficacy endpoint of the trial is the Final stent expansion %, defined as the minimum stent area (MSA) / mean reference lumen area assessed by OCT.	Measured by the data collected at the end of the PCI procedure
Target vessel failure (TVF)	The primary safety endpoint of the trial is target vessel failure (TVF), defined as a non-hierarchical composite endpoint of cardiovascular death, target-vessel myocardial infarction (TV-MI), and clinically indicated target vessel revascularization (CI-TVR).	1, 12, 36, and 60 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major cardiovascular adverse events	Major adverse cardiovascular events (MACE) is defined as a hierarchical composite of cardiovascular death, target-vessel myocardial infarction, clinically indicated target vessel revascularization, stent delivery failure, and suboptimal stent deployment. The between-group difference in terms of MACE will be compared using the Win Ratio approach in the abovementioned order.	1, 12, 36, and 60 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Suboptimal stent deployment	Suboptimal stent deployment is defined as fulfilling any of the following criteria: minimum stent area (MSA) ≤4.5mm2 (by OCT), MSA/mean reference lumen area ≤80%, flow-limiting dissections, or incomplete stent apposition (axial distance ≥0.4 mm and length ≥1 mm)	Measured by the data collected at the end of the PCI procedure
Stent delivery failure		Measured by the data collected at the end of the PCI procedure
Cardiac cause death		1, 12, 36, and 60 months
Target vessel myocardial infarction (TV-MI)		1, 12, 36, and 60 months
Clinically indicated target lesion revascularization (CI-TLR)		1, 12, 36, and 60 months
Clinically indicated target vessel revascularization (CI-TVR)		1, 12, 36, and 60 months
All cause death		1, 12, 36, and 60 months
Any stroke		1, 12, 36, and 60 months
Any MI		1, 12, 36, and 60 months
Any revascularisation		1, 12, 36, and 60 months
Patient-oriented composite endpoint (PoCE)	Patient-oriented composite endpoint (PoCE) is defined as all-cause death, any stroke, any MI, and any clinically indicated revascularisation	1, 12, 36, and 60 months
Definite/Probable Stent thrombosis rates	According to ARC-II classification	1, 12, 36, and 60 months
Peri-procedural MI	According to SCAI definition	48 hours
Peri-procedural major adverse events	Peri-procedural major adverse events were defined as a composite of the procedure of periprocedural MI, flow-limiting dissections, perforation/rupture, acute occlusion, slow-flow/no-reflow, ventricular tachycardia/ventricular fibrillation within 30 days	30 days
Acute gain	Acute gain is the difference between post- and pre-procedural minimal lumen diameter (MLD) as measured in (preferable) identical orthogonal views by OCT (MLDpost - MLDpre)	Measured by the data collected at the end of the PCI procedure
The difference between post- and pre-procedural FFR/IMR	FFR/IMR can be measured either by wire or derived from coronary angiography	Measured by the data collected at the end of the PCI procedure
Procedure time of the PCI		Measured by the data collected at the end of the PCI procedure
Radiation dose of the PCI		Measured by the data collected at the end of the PCI procedure
Contrast volume		Measured by the data collected at the end of the PCI procedure
Calcium fracture		Measured by the data collected at the end of the PCI procedure
Angiographic success	Angiographic success is defined as the ability of the allocated treatment to produce residual stenosis <20% after stenting without serious angiographic complications (severe dissection impairing flow [type D-F], perforation, abrupt closure, persistent slow flow, or no-reflow).	Measured by the data collected at the end of the PCI procedure
Strategy success	Strategy success is defined as Angiographic success without treatment crossover or stent loss	Measured by the data collected at the end of the PCI procedure
Clinical (Procedural) success	Clinical (Procedural) success is defined as Device success without the occurrence of in-hospital cardiovascular death, target-vessel myocardial infarction, or clinically indicated target vessel revascularization.	1 month
Coronary flow velocity	Coronary flow velocity is measured by Quantitative Flow Ratio (QFR)	Measured by the data collected at the end of the PCI procedure
TIMI Flow		Measured by the data collected at the end of the PCI procedure
Stent malapposition		Measured by the data collected at the end of the PCI procedure
Stent volume / reference lumen volume	Assessed by OCT	Measured by the data collected at the end of the PCI procedure
Mean stent area / Mean reference lumen area	Assessed by OCT Assessed by OCT	Measured by the data collected at the end of the PCI procedure

Collaborators and Investigators

• Sponsor: Xijing Hospital
• Investigators: Study Chair: Ling Tao, M.D, Ph.D., Xijing Hospital; Study Chair: Chao Gao, M.D, Ph.D., Xijing Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 5, 2024
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): March 1, 2025

Study Registration Dates

• First Submitted: January 16, 2024
• First Submitted That Met QC Criteria: January 25, 2024
• First Posted (Actual): February 2, 2024

Study Record Updates

• Last Update Posted (Actual): February 2, 2024
• Last Update Submitted That Met QC Criteria: January 25, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: percutaneous coronary intervention; Intravascular Lithotripsy; Severely Calcified Coronary Stenoses
• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Pathological Conditions, Anatomical; Coronary Disease; Constriction, Pathologic; Coronary Stenosis
• Other Study ID Numbers: KY20232390-C-1

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No