Intravascular Balloon Lithotripsy in Left Main Stem Percutaneous Coronary Intervention

The IVL Left Main study is a prospective non-randomised pilot study to investigate the mechanical and procedural outcomes and safety of distal left main stenting with coronary lithotripsy in addition to standard techniques in patients with calcific left main disease and a clinical indication for revascularisation.

Study Overview

• Status: Unknown
• Conditions: Left Main Coronary Artery Disease; Coronary Artery Calcification
• Intervention / Treatment: Device: Left main stenting with intravascular lithotripsy

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Claudia Cosgrove; Phone Number: 02087252807; Email: Claudia.Cosgrove@nhs.net
• Study Contact Backup: Name: Giovanna Bonato; Phone Number: 02087252807; Email: gbonato@sgul.ac.uk

Study Locations

• United Kingdom
  • Bristol, United Kingdom
    • University Hospitals Bristol NHS Foundation Trust
    • Contact: Julian Strange; Email: Julian.Strange@UHBristol.nhs.uk
  • London, United Kingdom
    • King's College Hospital NHS Foundation Trust
    • Contact: Ian Webb; Email: IanWebb@nhs.net
  • London, United Kingdom
    • St George's University Hospitals NHS Foundation Trust
    • Contact: Claudia Cosgrove; Email: Claudia.Cosgrove@nhs.net
  • London, United Kingdom
    • Royal Brompton & Harefield NHS Foundation Trust
    • Contact: Jonathan Hill; Email: J.Hill@rbht.nhs.uk
  • Northern Ireland
    • Belfast, Northern Ireland, United Kingdom
      • Belfast Health & Social Care Trust
      • Contact: Simon Walsh; Email: simon.j.walsh@btinternet.com
  • Scotland
    • Clydebank, Scotland, United Kingdom
      • Golden Jubilee Hospital
      • Contact: Margaret McEntagert; Email: margaret.mcentegart@nhs.net

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subject is ≥ 18 years old.

• Unprotected distal LM (or equivalent) disease defined as:

  1. >70% diameter stenosis (DS) on angiography in the distal LM; or
  2. ≥50% DS in the distal LM with a) non-invasive evidence of ischaemia referable to a hemodynamically significant left main lesion, and/or b) FFR ≤0.80; or
  3. >70% diameter stenosis in either the ostial left anterior descending (LAD) or ostial left circumflex (LCX) that is within 10 mm of the ostium and requires stenting back into the LM (distal LM equivalent); or
  4. >50% diameter stenosis in either the ostial left anterior descending (LAD) or ostial left circumflex (LCX) that is within 10 mm of the ostium and requires stenting back into the LM (distal LM equivalent) with a) non-invasive evidence of ischaemia referable to its myocardial territory and/or b) FFR ≤0.80
• Clinical indication for revascularisation by PCI
• Viability of the treatment vessel as determined by echocardiography, cardiac MRI or other equivalent imaging modality.
• ≥ 270° arc of calcification within at least one stenotic segment demonstrated on intravascular imaging.
• Ability to pass a 0.014" guide wire across the lesion.
• Ability to provide informed consent and comply with all study procedures, including follow-up at 30 days.

• Lesions not related to the distal LM requiring PCI can be treated:

  1. at the time of the study procedure if completed prior to distal LM PCI and the procedure was successful and uncomplicated (defined as a final lesion angiographic diameter stenosis <30% and TIMI 3 flow (visually assessed) for all non-target lesions and vessels without perforation, cardiac arrest or need for defibrillation or cardioversion or hypotension/heart failure requiring mechanical or intravenous hemodynamic support or intubation. In situations where the distal LM lesion is critical, the LM can be ballooned or treated first so long as the study protocol is not deviated.
  2. as a staged procedure either within the same hospital admission or within 30 days. Any staged procedure must be declared at the index procedure otherwise it will be recorded as an event.

Exclusion Criteria:

• Subject is participating in another research study involving an investigational agent (pharmaceutical, biologic, or medical device) that has not reached the primary endpoint.
• Daughter vessel reference diameter < 2.5 mm.
• Use of rotational atherectomy, scoring or cutting balloon, or any investigational device.
• Evidence of aneurysm in target vessel within 10 mm of the target lesion.
• Prior PCI of the LM or PCI of the proximal LAD or proximal LCX within 10 mm of the ostium.
• Prior coronary artery by-pass graft (CABG) surgery.
• Chronic total occlusion (CTO) of the LM, proximal LAD or proximal LCX.
• Untreated pre-procedural haemoglobin < 8 g/dL.
• Renal failure with serum creatinine > 2.5 mg/dL and not on chronic dialysis.
• Uncontrolled diabetes defined as a HbA1c >10%.
• Coagulopathy manifested by platelet count < 50,000/ mL or International Normalized ratio (INR) > 1.7 (INR is only required in patients who have taken warfarin within 2 weeks of enrolment).
• Cardiogenic shock.
• Ongoing ST elevation myocardial infarction (STEMI).
• History of stroke or transient ischemic attack (TIA) within 3 months.
• NYHA class IV heart failure or LVEF < 20%.
• Active peptic ulcer or upper gastrointestinal (GI) bleeding within 6 months.
• Patients with a life expectancy of less than 1 year.
• Visible thrombus (by angiography) at target lesion site.
• Patient has active systemic infection on the day of the index procedure with either fever or requiring intravenous antibiotics.
• Patient has vascular connective tissue disease (e.g. Marfan's syndrome).
• Patient has a hypercoagulable disorder.
• Patient has allergy to imaging contrast media for which they cannot be pre-medicated.
• Allergy to Aspirin.
• Allergy to Clopidogrel, Ticagrelor and Prasugrel.
• Allergy to any component of the drug eluting stent that is planned for use.
• Patient has any other severe comorbidity that is felt to preclude enrolment by the investigator.
• Subject is pregnant or nursing (a negative pregnancy test is required for women of child-bearing potential within 7 days prior to enrolment).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PCI to left main with IVL	Device: Left main stenting with intravascular lithotripsy; Intravascular lithotripsy (IVL) will be used to modify coronary artery calcification prior to stent implantation in left main coronary disease. Intravascular ultrasound (IVUS) will be used pre and post IVL and post stenting.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary effectiveness endpoint 1	Mean MSA (mm2) by segment for segments with obstructive disease and ≥ 270 degrees calcification.	Time of procedure
Primary effectiveness endpoint 2	Incidence of residual area stenosis <50% by segment for segments with obstructive disease and ≥ 270 degrees calcification.	Time of procedure
Primary safety endpoint	Incidence of Major Adverse Cardiac Events (MACE) at 30 days MACE consists of cardiac death, myocardial infarction and target vessel revascularisation	30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Minimum stent diameter (MSD) (mm) for segments with obstructive disease and ≥ 270 degrees calcification		Time of procedure
Stent symmetry ratio for segments with obstructive disease and ≥ 270 degrees calcification		Time of procedure
Stent expansion index (%) for segments with obstructive disease and ≥ 270 degrees calcification		Time of procedure
MSA (mm2) for all segments.		Time of procedure
MSD (mm) for all segments.		Time of procedure
Stent symmetry ratio for all segments.		Time of procedure
Stent expansion (%) for all segments.		Time of procedure
Device crossing success	ARC-2 criteria	Time of procedure
Angiographic success	ARC-2 criteria	Time of procedure
Procedural success	ARC-2 criteria	Time of procedure
Serious angiographic complications	ARC-2 criteria. Composite of loss of major vessel/side branch, embolisation, disruption of collateral flow, persistent slow-flow or no reflow, major dissection, new regional wall motion abnormality, imaging evidence of loss of viable myocardium.	24-48 hours
MACE at 12 months		12 months
Individual components of MACE at 30 days		30 days
Individual components of MACE at 12 months		12 months
Canadian Cardiovascular Society (CCS) angina status at 30 days		30 days
Canadian Cardiovascular Society (CCS) angina status at 12 months		12 months
Stroke at 30 days		30 days
Stroke at 12 months		12 months
Target lesion failure (TLF) at 30 days		30 days
Target lesion failure (TLF) at 12 months		12 months
Target vessel failure (TVF) at 30 days		30 days
Target vessel failure (TVF) at 12 months		12 months
All-cause mortality	Stratified by i) cardiac death ii) non-cardiac death	12 months
Peri-procedural myocardial infarction	ARC-2 criteria	48 hours
Spontaneous myocardial infarction	ARC-2 criteria	12 months
Ischaemic-driven revascularisation		12 months
All revascularisation		12 months
Angiographic and intracoronary imaging predictors of mechanical and procedural outcomes		12 months
Correlation between CK-MB and/or troponin levels post-PCI and outcomes at 30-days and 12 months		12 months

Collaborators and Investigators

• Sponsor: St George's, University of London
• Collaborators: St George's University Hospitals NHS Foundation Trust; Shockwave Medical, Inc.
• Investigators: Principal Investigator: James Spratt, St George's University Hospitals NHS Foundation Trust

Study record dates

Study Major Dates

• Study Start (Anticipated): May 1, 2020
• Primary Completion (Anticipated): March 1, 2022
• Study Completion (Anticipated): March 1, 2022

Study Registration Dates

• First Submitted: February 27, 2020
• First Submitted That Met QC Criteria: March 20, 2020
• First Posted (Actual): March 24, 2020

Study Record Updates

• Last Update Posted (Actual): March 24, 2020
• Last Update Submitted That Met QC Criteria: March 20, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Keywords: Coronary artery disease; Atherosclerosis
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease
• Other Study ID Numbers: 2019.0329

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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