The Prevent Coronary Artery Disease Trial
Icahn School of Medicine at Mount Sinai
1,600 participants
Sep 12, 2024
INTERVENTIONAL
Conditions
Summary
Despite increasing evidence that exposure to cardiovascular risk factors (CVRF) at an early age increases the prevalence of subclinical atherosclerosis and is associated with a greater risk of cardiovascular events later in life, there is a lack of randomized trial evidence to support primary prevention strategies in adults aged 30-50 years. The researchers have designed a randomized controlled trial to evaluate whether strict control of CVRF in young adults without known cardiovascular disease, will reduce the progression of total atherosclerosis burden, a surrogate endpoint for symptomatic cardiovascular disease, compared with usual care. The researchers propose a randomized controlled trial enrolling 1,600 healthy young adults who meet the inclusion criteria and who do not meet any exclusion criteria. Eligible study participants will be randomized, in a 1:1 ratio, to either the intervention group (active treatment strategy) or to the control group (guideline-directed medical therapy). Randomization will be stratified by the presence or absence of atherosclerotic plaque in vascular ultrasound.
Eligibility
Inclusion Criteria18
- 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 Criteria18
- 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.
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Interventions
Subjects will be administered a single subcutaneous injection of 284 mg inclisiran for injection at predefined time points.
Locations(1)
View Full Details on ClinicalTrials.gov
For the most up-to-date information, visit the official listing.
NCT06494501