Effect of Icosapent ethyl on inflammation in the vessel wall assessed by the Fat Attenuation Index Score (IRIS-FAI)

Not Applicable

• Conditions: Cardiovascular disease, hypertriglyceridemia; Circulatory System

• Registration Number: ISRCTN15140257
• Lead Sponsor: Imperial College London

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2024-08-22
• Last Update Posted: 2 September 2024
• Study Completion: 2026-07-01

Recruitment & Eligibility

• Status: Ongoing
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

1. Adult aged =18 years old
2. Participants will come from one of the following groups:
2.1. Enrolled in the ORFAN registry OR
2.2. Undergone CTCA with CaRi-Heart® analysis performed
3. CTCA performed = 2 months before screening [defined as screening]
4. FAI score = 75th percentile in the left anterior coronary or right coronary artery or with FAI score = 95th percentile in the circumflex coronary artery; OR CaRi-Heart® Risk >5%
5. Evidence of established coronary artery disease defined by the presence of at least one of the following:
5.1. Evidence of coronary artery plaques (evaluable, pre-randomization CTCA with quantifiable, non-calcified plaque in an unstented segment)
Or Coronary artery Calcium Score (CAC) > 100
6. Fasting or non-fasting serum triglycerides =1.7mmol/L within the last 6 months either on ORFAN baseline blood sample or blood sample taken from routine care, whichever is available and/or most recent
7. Stable dose of statin therapy for >30 days before randomization
8. Able to undergo CT imaging of the coronary arteries at 12 months follow-up
9. Women of childbearing potential willing to use an acceptable method(s) of birth control during the study and for 30 days after the end of treatment, including Combined hormonal contraception (oral contraceptive pills, contraceptive patch, vaginal ring), Progestogen-only contraception (oral contraceptive pills, injectable, implant, intrauterine device [IUD], hormonal intrauterine system [IUS]), Barrier methods with spermicide (condoms, diaphragm with spermicide), Intrauterine device (IUD) without hormones, and Sterilization (surgical sterilization of the participant or partner). There are no protocol-specific birth control requirements for men with partners who can become pregnant.
10. Willing and able to provide written informed consent to participate in the study

Exclusion Criteria

1. Use of other omega 3 fatty acid medicines either prescription or over the counter within the previous 28 days
2. Known allergy or hypersensitivity to icosapent ethyl or any of its components
3. History of pancreatitis or uncontrolled diabetes mellitus (HbA1c > 8% or 10.1 mmol/L)
4. Use of PCSK9 inhibitors within the previous 90 days
5. Use of Bile Acid sequestrants within the previous 7 days
6. Serum triglycerides >5.63mmol/L
7. Serum calculated or directly measured LDL-C =2.6mmol/L
8. Current use of anticoagulant therapy
9. Prior history of permanent or persistent Atrial Fibrillation. Patients with a history of paroxysmal atrial fibrillation are eligible
10. Any condition that, in the opinion of the study investigator, would make a patient ineligible for icosapent ethyl as per the SmPC, or for CTCA
11. Active chronic treatment with any anti-inflammatory agents (e.g. NSAIDs, systemic corticosteroids)
12. Severe Chronic kidney disease (estimated glomerular filtration rate < 30 mL/min/1.73 m² and/or serum creatinine > 2.5 mg/dL or 220 µmol/l).
13. Hepatic dysfunction (aspartate aminotransferase [AST] or alanine aminotransferase [ALT] > 3 × the upper limit of normal [ULN] measured on local labs in last 6 months)
14. Participants who have participated in another research study involving a treatment intervention or an investigational product, in the past 12 weeks.
15. Contraindication to iodinated contrast media for CTCA.
16. Pregnancy or unwilling to take a pregnancy test at the randomisation visit or lactating women.

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Median change in coronary artery inflammation measured using the Fat Attenuation Index-Score from screening to 12 months, IPE vs standard of care, including all randomized participants (Intention to treat)

Secondary Outcome Measures

Name	Time	Method
1. Median change in CaRi-Heart® Risk, and the associated predicted 8-year risk of cardiac mortality and major adverse cardiovascular events, with IPE vs standard of care (comparison by change from screening to 12 months, IPE vs standard of care)<br>2. Median change in non-calcified plaque volume and total atherosclerotic plaque burden between screening CTCA and 12-month CTCA, IPE vs usual care<br>3. Median change in plasma lipid parameters, from screening to 12 months