Intracoronary Cryotherapy Effect on Stabilization of Vulnerable Plaque in Patients With Stable Angina or ACS - A Traditional Feasibility Study (ICECAP)

Clinical Investigation of the Efficacy and Safety of Intracoronary Cryotherapy Using the CryoTherapy System (CTS) for High-risk Plaque in Patients With Stable Angina or Acute Coronary Syndrome.

ICECAP is a multi-centre, prospective, single-arm, interventional, traditional feasibility clinical investigation to evaluate the efficacy and safety of intra-coronary cryotherapy on vulnerable or high-risk plaque (HRP), using the CryoTherapy System (CTS). The study aims to enroll 25 patients with symptomatic coronary artery disease, successfully treated for their culprit lesion and with presence of at least one HRP lesion in another vessel. Eligible patients will undergo cryotherapy during a planned procedure. Near-infrared spectrometry (NIRS and Optical Coherence Tomography imaging will be used during baseline procedure, and during a 9 months follow visit. The primary endpoint is reduction of plaque burden measured as 30% reduction in maxLCBI4mm as measured by NIRS at 9 months post procedure.

Study Overview

• Status: Recruiting
• Conditions: Plaque; Cryotherapy Effect; Cryotherapy; Atherosclerosis Coronary Artery With Angina Pectoris; Vulnerable Plaque; Coronary Arterial Disease (CAD); Coronary Balloon
• Intervention / Treatment: Device: Intracoronary Cryotherapy

Detailed Description

ICECAP is a multi-centre, prospective, single-arm, interventional, traditional feasibility clinical investigation to evaluate the efficacy and safety of intra-coronary cryotherapy on vulnerable or high-risk plaque (HRP), using the CryoTherapy System (CTS). The study aims to enroll 25 patients with stable angina or Acute Coronary Syndrome (ACS). Patients who have undergone successful treatment of their culprit lesion, and in whom presence of at least one non-flow-limiting HRP lesion in another vessel is identified (confirmed by Coronary Computed Tomography Angiography - CCTA), are eligible for the study. Eligible patients will undergo cryotherapy using the CTS during a planned procedure within maximum 8 weeks after eligibility has been confirmed. Near-infrared spectrometry (NIRS) and Optical Coherence Tomography (OCT) imaging will be used during baseline procedure, and during a 9 months angiographic follow visit. Clinical follow-up visits will be done at 1, 3, 6, 9 and 12 months post-procedure. The primary endpoint is reduction of plaque burden, defined as 30% reduction in maxLCBI4mm measured by NIRS at 9 months post procedure. Secondary efficacy endpoints include: changes in fibrous cap thickness assessed by OCT at 9 months post-procedure, changes in Plaque volume and plaque composition at 9 months post-procedure. Safety endpoints include procedural success rates, any cryotherapy related complication or any Major Adverse Cardiac Event (MACE) at 3 and 12 months post procedure. The enrolment period is expected to last 9 months, and all subjects will be followed for 12 months after the CTS procedure.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Danny Detiege, RN; Phone Number: +32 467 02 47 73; Email: dde@cryotherapeutics.com
• Study Contact Backup: Name: Elisa Rossetti, MSc, Biomedical engineering; Phone Number: +3242644773; Email: ero@cryotherapeutics.com

Study Locations

• Belgium
  • Aalst, Belgium, 9300
    • Recruiting
    • AZORG Aalst
    • Contact: Adriaan Wilgenhof, MD; Phone Number: +32 53 72 49 96; Email: adriaan.wilgenhof@azorg.be
    • Contact: Hilde Delacroix, RN; Phone Number: +32 53724168; Email: hilde.deacroix@azorg.be
    • Principal Investigator: Adriaan Wilgenhof, MD
• United Kingdom
  • London, United Kingdom, EC1A 7BE
    • Not yet recruiting
    • St Bartholomew'S Hospital
    • Principal Investigator: Dan Jones, MD
    • Contact: Dan Jones, MD; Phone Number: +44 20 7377 7000; Email: dan.jones8@nhs.net
  • London, United Kingdom, SW3 6NP
    • Not yet recruiting
    • Royal Brompton Hospital
    • Principal Investigator: Ranil De Silva, MD
    • Contact: Ranil de Silva, MD; Phone Number: +44 20 7352 8121; Email: ranil.desilva@nhs.net

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 1) Subject is at least 18 years old. 2) Subject has acute cardiac pain/angina consistent with stable angina or 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 PCI within 72 hours from diagnosis
  2. Unstable angina
  3. ST-segment elevation myocardial infarction (STEMI) 3) Successful PCI (defined as diameter stenosis less than 30% and TIMI 3 flow on final angiography without procedural complication) of the culprit lesion.

NOTE: subjects with unstable angina, for whom the culprit lesion as assessed by investigator does not require PCI currently or within the next 6 months (subject treated with optimal medical treatment) can be enrolled in the study.

4) Subject has at least one high-risk plaque meeting the criteria below:

1. Located in a non-culprit vessel,

2. High-risk plaque lesion on CCTA and at least one of the following features:

   1. Presence of low-attenuation plaque (HU<50) and/or
   2. Positive remodelling (remodelling index >1.1) and/or
   3. Napkin ring sign and/or
   4. Plaque burden ≥70%
3. Lesion length ≤ 20 mm.
4. Diameter stenosis on invasive angiography between 30% and 70% on coronary angiogram or negative physiology assessment (FFR>0.80 or NHPR>0.89).
5. Reference vessel diameter (RVD) < 3.75 mm and > 2.50 mm in diameter
6. Investigator considers that lesions are accessible.

7. If more than two suitable lesions available, investigator will select the most appropriate lesion for cryotherapy treatment.

   5) maxLCBI4mm in the lesion > 324.7 6) Subject is able to provide consent and has signed and dated the informed consent form.

   Exclusion Criteria:

   • 1) Subject is hemodynamically unstable (cardiogenic shock, hypotension needing inotropes, hypoxia needing intubation, refractory ventricular arrhythmias, and IABP).

     2) Subject has ongoing ST-segment elevation myocardial infarction. 3) Subject had a procedural complication during the ACS PCI procedure. 4) Subject has history of Coronary Artery Bypass Graft (CABG) or planned CABG within 12 months after the index procedure.

     5) Subject has known reduced Left Ventricular Ejection Fraction < 30%. 6) Subject has known severe valvular heart disease. 7) Subject has known severe renal insufficiency (eGFR <30 ml/min/1.72 m2). 8) Subject has any life-threatening conditions or medical comorbidity resulting in life expectancy < 12 months.

     9) Subject is currently participating in another clinical investigation that has not yet reached its primary endpoint.

     10) Subject has severe peripheral vascular disease impeding femoral artery access.

     11) Subject is pregnant or lactating, or NOT surgically sterile (tubal ligation or hysterectomy) or NOT postmenopausal for at least 6 months or is a female with childbearing potential without effective contraception (pill, patch, ring, diaphragm, implant and intrauterine device).

   Angiographic exclusion criteria:

   1. Visible distal embolization/no-reflow following culprit lesions PCI.
   2. Left main coronary artery disease (visual diameter stenosis > 50%).
   3. Stent thrombosis/restenosis as a culprit lesion.
   4. CTS lesion involving a bifurcation (defined as lesions involving side branches >2.0 mm).
   5. Angiographic or CCTA evidence of severe calcification and/or marked tortuosity of the index vessel and/or lesion.
   6. Thrombotic lesions.
   7. Ostial lesions.

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: Treatment arm; Subjects with coronary HRP lesions treated with intracoronary cryotherapy using the CTS device	Device: Intracoronary Cryotherapy; Intracoronary cryotherapy for stabilization of High-risk coronary plaque

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary efficacy endpoint	Reduction of in maxLCBI4mm in the lesion measured by NIRS	At 9 months post-CTS procedure compared to baseline.
co-primary safety endpoint	Rate of Cryotherapy procedure related complications or MACE	at 30 days post procedure

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Fibrous Cap Thickness	Change in OCT-derived fibrous cap thickness	At 9 months post-CTS procedure compared to baseline
Change in Minimal Lumen Area (MLA)	Change in minimum lumen area (MLA) by OCT	At 9 months post-CTS procedure compared to baseline.
Prevalence of Thin Cap Fibrous Atheroma	Prevalence of thin cap fibroatheroma (minimum fibrous cap thickness < 65 µm with lipid arc > 90°) by OCT.	At 9 months post-CTS procedure compared to baseline.
Prevalence of lipid Arc >90°	Prevalence of lipid arc greater than 90° by OCT.	At 9 months post-CTS procedure compared to baseline.
Prevalence of lipid Arc >180°	Prevalence of lipid arc greater than 180° by OCT.	At 9 months post-CTS procedure compared to baseline.
Prevalence of lipid Arc >270°	Prevalence of lipid arc greater than 270° by OCT.	At 9 months post-CTS procedure compared to baseline.
Total angle of macrophage	Total angle of macrophage within the treated segment by OCT.	At 9 months post-CTS procedure compared to baseline.
Maximum angle of macrophage	Maximum angle of macrophage within the treated segment by OCT.	At 9 months post-CTS procedure compared to baseline.
Total angle of lipidic plaque	Total angle of lipidic plaque within the treated segment by OCT.	At 9 months post-CTS procedure compared to baseline.
Maximum angle of lipidic plaque	Maximum angle of lipidic plaque within the treated segment by OCT.	At 9 months post-CTS procedure compared to baseline.
Total angle of calcification	Total angle of calcification within the treated segment by OCT.	At 9 months post-CTS procedure compared to baseline.
Maximum angle of calcification	Maximum angle of calcification within the treated segment by OCT.	At 9 months post-CTS procedure compared to baseline.
Total Plaque volume	Total Plaque volume within the treated lesion segment assessed by CCTA	At 12 months post-CTS procedure compared to baseline.
Calcified Plaque volume	Calcified Plaque volume within the treated lesion segment assessed by CCTA	At 12 months post-CTS procedure compared to baseline.
Area stenosis	Area stenosis within the treated lesion segment assessed by CCTA	At 12 months post-CTS procedure compared to baseline.

Collaborators and Investigators

• Sponsor: Cryotherapeutics SA
• Collaborators: CoreAalst BV
• Investigators: Study Chair: Carlos Collet, MD, Cardiovascular Research Foundation, New York, USA

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2025
• Primary Completion (Estimated): January 31, 2027
• Study Completion (Estimated): June 30, 2027

Study Registration Dates

• First Submitted: April 15, 2025
• First Submitted That Met QC Criteria: April 15, 2025
• First Posted (Actual): April 22, 2025

Study Record Updates

• Last Update Posted (Actual): April 6, 2026
• Last Update Submitted That Met QC Criteria: March 31, 2026
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: Interventional; Prospective; Medical device; Multi-Center; Device Feasibility; traditional feasibility; Single Group
• Additional Relevant MeSH Terms: Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms; Plaque, Amyloid
• Other Study ID Numbers: CT-CP-P01_0104

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