Pilot Study on the Effect of Intracoronary Cryotherapy on Stabilization of Vulnerable Plaque at Risk of Rupture

Atherosclerosis is a progressive inflammatory disease of the large and medium sized arteries, which is characterized by the formation of plaques in the vessel wall. The morphology and composition of the plaque play a major role in its stability during the development of the disease.

The CTS system allows to deliver coronary cryotherapy intended for stabilization of vulnerable plaque with non-significant stenosis. Vulnerable plaque at high risk of rupture will be assessed by NIRS-IVUS imaging modality in patients with Acute Coronary Syndrome (ACS).

The ICEBERG study is an early feasibility single arm study enrolling a maximum of 45 patients. After enrolment of the first 5 patients in the First-in-Man safety cohort, the trial will enroll and randomize 40 eligible lesions in the randomized cohort of which 20 will be treated with cryotherapy.


Eligibility Criteria:
Inclusion Criteria:

* Men or women at least 18 years old.
* Acute cardiac pain/angina consistent with acute coronary syndrome eligible for coronary angiography meeting one of the following criteria:

  1. Non ST-segment elevation myocardial infarction (NSTEMI) with rise/fall of cardiac enzymes (troponin I or T) with at least one value above the 99th percentile of the upper reference limit requiring Percutaneous Coronary Intervention (PCI) within 72 hours from diagnosis
  2. Stabilized ST-segment elevation myocardial infarction (STEMI) with at least one value above the 99th percentile of the upper reference limit requiring PCI within \< 12 hours from symptoms onset.
  3. Unstable angina with new or worsening angina symptoms over the last 2 weeks requiring PCI within 72 hours.
* Patient must have one, two or three-vessel disease in native coronary arteries.
* PCI of the culprit lesion on all patients.
* At least one lesion meeting the criteria below:

  1. Located in a non-culprit vessel, or proximal to the culprit lesion if located in the culprit vessel with at least 10 mm distance from the culprit lesion.
  2. Lesion stenosis ≤ 70% of the reference vessel diameter by visual assessment on coronary angiogram.
  3. Plaque-level maxLCBI4mm ≥ 325 by NIRS (Near-Infrared Spectroscopy).
  4. Plaque burden ≥ 65% by IVUS (IntraVascular UltraSound).
  5. Not intended for revascularization based on angiographic criteria and negative physiology assessment (FFR\>0.80 or iFR/RFR\>0.89).
  6. Lesion-level balloon to artery ratio \> 1.0.
  7. Lesion length ≤ 20 mm.
  8. Investigator considers that lesions are accessible.
  9. If more than two suitable lesions available, investigator will select two lesions for randomization.
* Subject able to consent and has a signed and dated the informed consent form.

Exclusion Criteria:

* Unstable patients (cardiogenic shock, hypotension needing inotropes, hypoxia needing intubation, refractory ventricular arrhythmias, and IABP).
* Patients with ongoing ST-segment elevation myocardial infarction.
* Patients that had a procedural complication during the PCI procedure, such as coronary dissection, perforation or a complication that would necessitate immediate and/or unplanned surgical revascularization.
* History of Coronary Artery Bypass Graft (CABG) or planned CABG within 12 months after the index procedure.
* Known ejection fraction \< 30%.
* Known severe valvular heart disease.
* Known severe renal insufficiency (eGFR \<30 ml/min/1.72 m2).
* Any life-threatening conditions or medical comorbidity resulting in life expectancy \< 12 months.
* Participation in any investigational study that has not yet reached its primary endpoint.
* Women who are pregnant or lactating, or NOT surgically sterile (tubal ligation or hysterectomy) or NOT postmenopausal for at least 6 months or women with childbearing potential without effective contraception (pill, patch, ring, diaphragm, implant and intrauterine device).

Angiographic exclusion criteria:

* Visible distal embolization/no-reflow following culprit PCI.
* Left main coronary artery disease (visual diameter stenosis \> 50%).
* Stent thrombosis/restenosis as a culprit lesion.
* Index lesion involving a bifurcation.
* Angiographic evidence of severe calcification and/or marked tortuosity of the index vessel and/or lesion.