pilot study on the effect of intracoronary cryotherapy on stabilization of vulnerable plaque at risk of rupture

Conditions: Acute Coronary Syndrome

Summary: 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.