The Prevent Coronary Artery Disease Trial

Launched by ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · Jul 2, 2024

Keywords

ClinConnect Summary

The Prevent Coronary Artery Disease Trial is a clinical study aimed at understanding whether closely managing heart-related risk factors in young adults can help reduce the buildup of artery plaque, which can lead to heart disease. This study is focusing on healthy adults aged 30 to 50 who do not have any known heart disease but may show early signs of atherosclerosis, which is the hardening of the arteries due to plaque buildup. Researchers plan to enroll 1,600 participants and will divide them into two groups: one group will receive an active treatment plan, while the other group will follow standard care guidelines.

To be eligible for this trial, participants must be between 30 and 50 years old, have no history of serious heart conditions, and show signs of early atherosclerosis. This could be indicated by certain blood test results or imaging tests that show plaque in the arteries. Participants can expect to receive regular check-ups and treatment as part of the study, and their progress will be monitored closely. It's important for potential participants to know that the study has specific guidelines, and those with certain medical conditions or who are pregnant may not be able to take part.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • Male or female subjects between 30 to 50 years of age.
• • No prior history of coronary artery disease, cerebrovascular disease or peripheral artery disease.
• • Serum LDL-C \> 1.8 mmol/l (70 mg/dl).
• • Presence of subclinical atherosclerosis as assessed by 3DVUS or by the presence of coronary artery calcium (defined as coronary artery calcium score ≥25), independent of risk calculators; and/or high lifetime risk (≥30%) using the ASCVD calculator; and/or intermediate 10-year risk (≥7.5%) using the ASCVD calculator in the presence of 2 risk enhancers.
• • The presence of atherosclerotic plaque by 3DVUS will be defined according to the PESA study definitions14: plaque is defined as a focal protrusion into the arterial lumen of thickness \>0.5 mm or \>50% if the intima media thickness or intima media thickness \>1.5 mm. CT scan for coronary artery calcium assessment will not be part of the protocol but will be used where available.
• Risk enhancers are defined as15:
• • Family history of premature atherosclerotic CVD
• • Persistently elevated LDL-C ≥ 160 mg/dl
• • Chronic kidney disease
• • Metabolic syndrome
• • Conditions specific to women (e.g. preeclampsia, premature menopause)
• • Inflammatory diseases (especially rheumatoid arthritis, psoriasis, HIV)
• • Ethnicity (e.g., South Asian ancestry)
• • Persistently elevated triglycerides (≥175 mg/dl)
• • Hs-CRP ≥2 mg/L
• • Lp(a) levels \>50 mg/dl
• • apoB ≥130 mg/dl
• • Ankle-brachial index \<0.9
• Exclusion Criteria:
• • Any uncontrolled or serious disease, or any medical or surgical condition, that may either interfere with participation in the clinical study, and/or put the subject at significant risk (according to investigator's \[or delegate\] judgment) if he/she participates in the clinical study.
• • An underlying known disease, or surgical, physical, or medical condition that, in the opinion of the investigator (or delegate) might interfere with interpretation of the clinical study results.
• • Females who are pregnant or nursing, or who are of childbearing potential and unwilling to use at least two methods of highly effective contraception (failure rate less than 1% per year) (e.g. combined oral contraceptives, barrier methods, approved contraceptive implant, long- term injectable contraception, or intrauterine device) for the entire duration of the study.
• • Severe concomitant non-cardiovascular disease that carries the risk of reducing life expectancy to less than 5 years.
• • History of malignancy that required surgery (excluding local and wide-local excision), radiation therapy and/or systemic therapy during the three years prior to randomization
• • Active liver disease defined as any known current infectious, neoplastic, or metabolic pathology of the liver or unexplained elevations in ALT, aspartate aminotransferase (AST), \>3x the ULN, or total bilirubin \>2x ULN at screening confirmed by a repeat abnormal measurement at least 1 week apart.
• • Known contraindications to anti-lipid therapy
• • Known history of alcohol and/or drug abuse within the last 5 years.
• • Treatment with other investigational products or devices within 30 days or five half- lives of the screening visit, whichever is longer.
• • Planned use of other investigational products or devices during the course of the study.
• * Any condition that according to the investigator could interfere with the conduct of the study, such as but not limited to:
• • Subjects who are unable to communicate or to cooperate with the investigator.
• • Unable to understand the protocol requirements, instructions and study-related restrictions, the nature, scope, and possible consequences of the study (including subjects whose cooperation is doubtful due to drug abuse or alcohol dependency).
• • Unlikely to comply with the protocol requirements, instructions, and study- related restrictions (e.g., uncooperative attitude, inability to return for follow-up visits, and improbability of completing the study).
• • Have any medical or surgical condition, which in the opinion of the investigator would put the subject at increased risk from participating in the study.
• • Persons directly involved in the conduct of the study.
• • Treatment (within 90 days of screening) with monoclonal antibodies directed towards PCSK9.
• • History of hypersensitivity to the study treatment or its excipients or to other siRNA drugs.