The Prevent Coronary Artery Disease Trial
Study Phase: Phase 3
Recruitment Status: Recruiting
Start Date: July 01, 2024
End Date: June 30, 2032
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.
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.