The Use of Icosapent Ethyl on Vascular Progenitor Cells in Individuals With Elevated Cardiovascular Risk

• Status: Recruiting
• Trial end date: 2021-12-01
• Target enrollment: 0
• Participant gender: All

Summary

IPE-PREVENTION is a prospective, randomized, 3-month long, open-label study. A total of 70 individuals with elevated cardio-metabolic risk and heightened triglyceride levels, and who are on stable statin therapy will be randomized (1:1) to receive either icosapent ethyl (IPE) 2g BID or standard of care.

It is hypothesized that assignment to IPE will lower progenitor cell depletion as well as limit progenitor cell dysfunction. This study may offer some molecular and cellular insights into the mechanisms underlying the cardiovascular benefits of IPE therapy reported in the REDUCE-IT trial.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Canadian Medical and Surgical Knowledge Translation Research Group
• Collaborators: HLS Therapeutics, Inc; St. Michael's Hospital, Toronto; Unity Health Toronto; University of Western Ontario, Canada
• Treatments: Eicosapentaenoic acid ethyl ester

Criteria

Inclusion Criteria:

1. Women ≥65 years of age and men ≥40 years of age with established CVD (see criterion 'a' below) or ≥50 years of age with diabetes and one additional CV risk factor (see criterion 'b' below)

1. Those with established CVD should have ≥1 of the following clinical history

• Documented coronary artery disease (CAD)

• Prior MI

• Multivessel CAD (≥50% stenosis in ≥2 major epicardial coronary arteries)

• Hospitalization for high-risk non-ST-segment elevation acute coronary syndrome

• Documented cerebrovascular or carotid disease (≥1 of the following)

• Prior ischemic stroke

• Carotid artery disease with ≥50% stenosis

• History of carotid revascularization

• Documented peripheral artery disease (≥1 of the following)

• Ankle-brachial index (ABI) <0.9 with symptoms of intermittent claudication

• History of aorto-iliac or peripheral arterial intervention

2. Those with a history of diabetes (either type 1 or type 2 diabetes mellitus) but no CVD should also have ≥1 of the following:

• Cigarette smoker or stopped smoking within 3 months before the baseline visit

• Documented hypertension OR on antihypertensive agents

• HDL-C ≤1.0 mmol/L for men or ≤1.3 mmol/L for women

• High sensitivity C-reactive protein >3.0 mg/L

• eGFR 30 to 60 mL/min/1.73m2

• Documented micro- or macro-albuminuria

• Retinopathy

• Non-proliferative retinopathy

• Preproliferative or proliferative retinopathy

• Maculopathy

• Advanced diabetic retinopathy

• History of photocoagulation

• ABI <0.9 without symptoms of intermittent claudication

2. Elevated triglycerides (≥1.5 mmol/L but <5.6 mmol/L)

3. On stable statin therapy for ≥4 weeks at the baseline visit

4. Willing to provide written informed consent and be compliant with the study requirements

5. Willing and able to follow the diet recommended by the study doctor

Exclusion Criteria:

1. Participation in another clinical trial with an investigational agent ≤90 days prior to screening

2. Women who are of childbearing potential

3. Any condition or therapy which the study doctor thinks might pose a risk to the participant

4. Severe (New York Heart Association class IV) heart failure

5. Any life-threatening disease expected to result in death within the next 2 years

6. Diagnosis or laboratory evidence of active severe liver disease

7. HbA1c >10.0% at the baseline visit

8. SBP ≥200 mmHg or DBP ≥100 mmHg (despite being on antihypertensive therapy)

9. Planned coronary intervention or any non-cardiac major surgical procedure

10. Known familial lipoprotein lipase deficiency, apolipoprotein C-II deficiency, or familial dysbetalipoproteinemia

11. Statin intolerant or hypersensitivity to statin therapy

12. Require peritoneal dialysis or hemodialysis

13. eGFR <30 mL/min/1.73m2

14. History of atrial fibrillation

15. History of major bleeding event(s)

16. Documented history of pancreatitis

17. Malabsorption syndrome and/or chronic diarrhea

18. Known acquired immunodeficiency syndrome

19. Unexplained elevated creatine kinase concentration >5 × the upper limits of normal or elevation due to known muscle disease

20. Use of niacin, fibrates, omega-3 fatty acids, dietary supplements containing omega-3 fatty acids, bile acid sequestrants or PCSK9 inhibitors

21. Known hypersensitivity to fish and/or shellfish, or ingredients of IPE

22. Inability to swallow IPE capsules whole

23. Drug or alcohol abuse within the past 6 months, and inability/unwillingness to abstain from drug abuse and excessive alcohol consumption during the study

24. Mental/psychological concerns or any other reason to expect difficulty in complying with the study requirements or understanding the goal and potential risks of being a part of the study