The Value of IVL Compared To OPN Non-Compliant Balloons for Treatment of RefractorY Coronary Lesions (VICTORY) Trial (VICTORY)

The Value of IVL Compared To OPN Non-Compliant Balloons for Treatment of RefractorY Coronary Lesions (VICTORY) Trial - A Randomized, Multicenter, Non-inferiority Comparison of Shockwave Intravascular Lithotripsy (IVL) and the OPN Non-compliant Balloon for Treatment of Calcified and Refractory Coronary Lesions

Percutaneous coronary intervention (PCI) with drug-eluting stent (DES) implantation has become the dominant treatment strategy for patients with acute and chronic coronary artery disease (CAD) requiring revascularization. Nonetheless, PCI with stent implantation has some limitations and especially patients with severely calcified coronary lesions (approximately 10-20% of all patients with CAD) have an elevated risk for adverse outcomes, including target lesion failure (TLF) and stent thrombosis (ST).

Several dedicated PCI devices have been developed for treatment of severely calcified lesions. Whereas especially two of them have shown promising results in smaller, prospective studies. First, the super high-pressure NC PCI balloon (OPN™ NC, SIS Medical AG, Frauenfeld, Switzerland) has been shown to represent an effective and safe device for lesion preparation. Second, the lately introduced Shockwave intravascular lithotripsy (IVL)™ balloon catheter (Shockwave Medical, Santa Clara, CA, USA) appears to be a safe and efficient alternative device for treatment of calcified coronary lesions. However, it remains unknown, if the OPN™ NC balloon is non-inferior to to IVL regarding lesion preparation and completeness of stent expansion in severely calcified lesions.

Study Overview

• Status: Recruiting
• Conditions: Coronary Artery Disease; Coronary Disease; Coronary Artery Calcification; Stent Restenosis; Calcific Coronary Arteriosclerosis
• Intervention / Treatment: Device: OPN™ NCB Super High Pressure PCI Balloon; Device: Shockwave™ C2 IVL Catheter

Detailed Description

To evaluate final stent expansion following a strategy of lesion preparation with either the Shockwave C2 IVL™ Catheter (Shockwave Medical Inc. Santa Clara, CA, United States) or a super high-Pressure NC PTCA Balloon (OPN™ NC; SIS Medical Distribution AG, Frauenfeld, Switzerland) in patients with heavily calcified coronary lesions undergoing coronary stent implantation.

To assess the safety of a strategy of using super high-pressure NC balloons compared to shockwave IVL™ for treatment of heavily calcified lesions, which are treated with a contemporary drug eluting stent.

Patients presenting with chronic or acute coronary artery disease and requiring PCI to a very calcified coronary artery lesion will either be randomized to preparation of that corresponding lesion using the control device (Shockwave™ IVL balloon catheter) or the study device (the super high-pressure NC PCI Balloon (OPN™ NC)).

The treatment of the calcified coronary lesion will be guided by use of intravascular imaging (optical coherence tomography, OCT).

Enrolled patients will undergo follow-up at 30 days, 1 year and 2 years

• Study Type: Interventional
• Enrollment (Anticipated): 280
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Switzerland
  • Lucerne, Switzerland, 6000
    • Recruiting
    • Luzerner Heart Centre

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

Clinical inclusion criteria:

• Age ≥18 years and consentable;
• Acute or chronic coronary artery disease with ischemia related symptoms (e.g. angina) and/or evidence of myocardial ischemia (e.g. FFR/ iFR, CMR, SPECT or PET-CT);
• Angiographically-proven coronary artery disease;

• Lesions in non-target vessels requiring PCI may be treated either

  • prior to the study procedure if the procedure was unsuccessful or complicated; or
  • in the same session if feasible and safe for the patient, otherwise a staged PCI procedure for non-target vessels may be considered;
• Informed Consent signed by the subject.

Angiographic inclusion criteria:

• Single de novo target lesion stenosis of protected LMCA, or LAD, RCA or LCX (or of their branches) with:

  • Stenosis of ≥70%;
  • Stenosis ≥50% and <70% (visually assessed) with evidence of ischemia via positive stress test, or fractional flow reserve value ≤0.80, or iFR <0.90 or IVUS minimum lumen area ≤4.0 mm²;
• The target vessel reference diameter must be ≥2.5 mm & ≤4.5 mm;
• Evidence of calcification at the lesion site by angiography (Grade 3), with fluoroscopic radio-opacities noted without cardiac motion prior to contrast injection involving both sides of the arterial wall in at least one location and total length of calcium of at least 15 mm and extending partially into the target lesion,
• AND/ OR by OCT, with presence of ≥180° calcium or >120° calcium with 200µm of calcium thickness on at least 1 cross section.

Annotation: Only one lesion and vessel per randomized patient may be treated according to protocol and considered for the purpose of this study. The lesion considered for the study should represent the most calcified one.

The presence of any one of the following exclusion criteria will lead to the exclusion of the subject:

Exclusion criteria:

• Patient experienced an acute STEMI or cardiogenic shock related to an acute MI within 2 days prior to index procedure;
• Any comorbidity or condition which may reduce compliance with this protocol, including follow-up calls/ visits (e.g. advanced dementia);
• Any medical, geographic, and/or social factor making study participation impractical or precluding required follow-up.
• Patient is pregnant or nursing (a negative pregnancy test is required for women of child-bearing potential within 7 days prior to enrollment);
• Unable to take a P2Y12 inhibitor (i.e. clopidogrel, prasugrel, or ticagrelor) for at least 6 months;
• Patient has an allergy to imaging contrast media which cannot be adequately pre-medicated;
• Renal failure with an eGFR <30ml/min1.73m2;
• History of a stroke or transient ischemic attack (TIA) within 7 days, or any prior intracranial hemorrhage;
• Active peptic ulcer or upper gastrointestinal (GI) bleeding within 6 months;
• Untreated pre-procedural hemoglobin <10g/dL or intention to refuse blood transfusions if one should become necessary;
• Patient has an allergy or intolerance to cobalt-chromium and/ or everolimus.
• Life expectancy of less than 1 year.

Angiographic exclusion criteria:

• Anatomy where the device or OCT catheter are unlikely to be delivered due to tortuosity or other characteristics;
• Target lesion is in a coronary artery bypass graft;
• Target lesion is an in-stent restenosis (ISR);
• Flow limiting target vessel thrombus (evident on angiography or OCT);
• Definite or possible thrombus (by angiography or intravascular imaging) in the target vessel;
• Evidence of aneurysm in target vessel within 10 mm of the target lesion.

Of note, only qualified physicians who are investigators or a sub-investigators for the trial will assess each individual´s eligibility criteria and take the final decision to include the subject in the trial (ICH GCP 4.3.1). This decision will be documented prior to the subject receiving the first intervention.

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: Study Device	Device: OPN™ NCB Super High Pressure PCI Balloon; In order to permit advancement of the studied medical devices - OPN™ NCB or Shockwave™ IVL balloon catheter - initial lesion preparation using small SCBs or NCBs (≤2mm) or rotablation (Boston Scientific, Marlborough, MA, United States) is allowed, but will be documented. This may be required in selected cases with very calcified and tight lesions. As per protocol, lesion preparation will be performed using either the super-high pressure PCI balloon OPN™ NCB or the Shockwave™ IVL balloon catheter according to random treatment assignment after matching the angiographic and/or OCT inclusion criteria. Following successful lesion preparation all patients will be treated with a latest generation durable polymer everolimus-eluting stent (Xience™ Sierra or Skypoint, Abbott Vascular Inc., Santa Clara, CA, United States) to allow comparison of stent expansion.
Active Comparator: Control Device	Device: Shockwave™ C2 IVL Catheter; In order to permit advancement of the studied medical devices - OPN™ NCB or Shockwave™ IVL balloon catheter - initial lesion preparation using small SCBs or NCBs (≤2mm) or rotablation (Boston Scientific, Marlborough, MA, United States) is allowed, but will be documented. This may be required in selected cases with very calcified and tight lesions. As per protocol, lesion preparation will be performed using either the super-high pressure PCI balloon OPN™ NCB or the Shockwave™ IVL balloon catheter according to random treatment assignment after matching the angiographic and/or OCT inclusion criteria. Following successful lesion preparation all patients will be treated with a latest generation durable polymer everolimus-eluting stent (Xience™ Sierra or Skypoint, Abbott Vascular Inc., Santa Clara, CA, United States) to allow comparison of stent expansion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Final stent expansion (in percentage, %) assessed by OCT	At index Procedure

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acceptable stent expansion (>80%) assessed by OCT		At index Procedure
Optimal stent expansion (>90%) assessed by OCT		At index Procedure
Procedural success	defined as the achievement of angiographic success (residual stenosis of <30%, no flow-limiting dissection and/or no no-reflow) without any major adverse cardiac events (MACE), which is defined as cardiac death, target vessel related myocardial infarction, TIA/ stroke and repeat revascularization (PCI or CABG) up to 30 days	At index Procedure
Strategy success	defined as procedural success using the assigned study device and stent, without requirement for lesion preparation with further devices (i.e. cross-over to the non-assigned study devices or cutting/ scoring balloons).	At index Procedure

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Coronary perforations (Ellis grade III and/or cavity spilling)		At index Procedure
Persistent periprocedural vessel occlusion/MI		At index Procedure
Periprocedural ventricular tachycardia/fibrillation (VT/ VF)		At index Procedure
Contrast-induced nephropathy (CIN)		At index Procedure
Major bleeding (BARC 3-5)		At index Procedure, 30 days, 1 Year and 2 Years
Number of complementary lesion preparations with further devices (i.e. cutting or scoring balloons) or cross-over to the non-assigned study devices.		At index Procedure
Acute lumen gain	defined as minimal lumen diameter (MLD) post balloon angioplasty minus baseline MLD (mm) assessed by OCT	At index Procedure
Frequency of calcium fracture/s (CF) at the site of maximum calcium		At index Procedure
Procedure duration		At index Procedure
Procedure radiation exposure		At index Procedure
Procedure contrast volume		At index Procedure
Major Adverse Cardiac Events (MACE)	defined as cardiac death, target vessel related myocardial infarction, TIA/ stroke and repeat revascularization (PCI or CABG)	At 30 days, 1 Year and 2 Years
Target vessel revascularization (TVR)	TVR is defined as any revascularization within the entire major coronary vessels proximal or distal to a target lesion including upstream and downstream side branches and the target lesion itself.	At 30 days, 1 Year and 2 Years
Target lesion revascularization (TLR)	TLR is defined as any repeat percutaneous or surgical intervention due to a stenosis or occlusion within the stent or within the 5mm border proximal or distal to the stent.	At 30 days, 1 Year and 2 Years
Rate of new acute myocardial infarction (MI) (either NSTEMI/STEMI)	MI is defined according to the Fourth Universal Definition of Myocardial Infarction. Peri-procedural MI is defined according to the Society of Coronary Angiography Interventions (SCAI) and Fourth Universal Definition of Myocardial Infarction definitions. SCAI criteria define peri-procedural MI as creatin kinase myocardial band measured (CK-MB) within 48 hours of the procedure elevated ≥10 times above the upper limit of normal (ULN), or ≥5 times ULN with development of new pathologic Q waves in 2 contiguous electrocardiographic leads or new left bundle branch block. In the absence of CK-MB measurements, post-procedural MI is defined as a troponin value ≥70 times ULN, or ≥35 times ULN with new pathologic Q waves or new left bundle branch block. The SCAI criteria to define peri-procedural MI were also used for patients with elevated cardiac enzymes at baseline.	At 30 days, 1 Year and 2 Years
Rate of Stent thrombosis (ST)	According to ARC definition): Event certainty:Definite: Acute coronary syndrome with angiographic or autopsy confirmations of stent thrombosisProbable:i. Unexplained death within 30 days of stent implantation without autopsy. ii. Acute myocardial infarction in the territory of target vessel where stent was implanted but without angiographic confirmation.Possible: Unexplained death after 30 days of stent implantation without autopsy.; Time frame:Early:i. Acute - during the procedure of stent implantation (PCI) ii. Sub-acute - within 30 days after PCILate: 1-12 months after stent implantation (up to 1 year)Very late: After one year of stent implantation.	At 30 days, 1 Year and 2 Years
Rate of TIA or stroke	Stroke requires the presence of acute focal or global neurological dysfunction caused by brain or retinal vascular injury due to primary hemorrhage or infarction. Symptoms or signs must persist >24 hours or when acute stroke is present on brain imaging (i.e. if there is an acute/subacute stroke documented by CT or MRI or at autopsy, the duration of symptoms/signs may be less than 24 hours). Global symptoms/signs are restricted to subarachnoid hemorrhage. Subarachnoid hemorrhage does not require focal neurological deficits, and the diagnosis is based on the clinical syndrome plus imaging as described below.	At 30 days, 1 Year and 2 Years
Rate of Cardiovascular death	Cardiac death will be defined in accordance with the Academic Research Consortium (ARC) as any death due to a proximate cardiac cause (e.g. myocardial infarction, low-output failure, fatal arrhythmia), unwitnessed death and death of unknown cause. All procedure-related deaths, including those related to concomitant treatment, will be classified as cardiac death.	At 30 days, 1 Year and 2 Years
Rate of all-cause death	Includes death from any cause. The cause of death will be adjudicated.	At 30 days, 1 Year and 2 Years

Collaborators and Investigators

• Sponsor: Luzerner Kantonsspital

Study record dates

Study Major Dates

• Study Start (Actual): November 22, 2022
• Primary Completion (Anticipated): December 31, 2024
• Study Completion (Anticipated): May 30, 2027

Study Registration Dates

• First Submitted: March 31, 2022
• First Submitted That Met QC Criteria: April 19, 2022
• First Posted (Actual): April 26, 2022

Study Record Updates

• Last Update Posted (Actual): January 23, 2023
• Last Update Submitted That Met QC Criteria: January 19, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arterial Occlusive Diseases; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Arteriosclerosis
• Other Study ID Numbers: VICTORY trial

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No