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.

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

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 & ≤4.5mm;

• AND AT LEAST ONE OF THE FOLLOWING CRITERIA:

  • 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 ≥270° calcium;
  • AND/ OR Prior attempt at PCI with inability to expand a balloon in target lesion.

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.

Prospective, randomized, multicenter, non-inferiority trial with blinded assessment of outcomes (PROBE design)