Preventing coronary artery disease in young adults

The Prevent Coronary Artery Disease Trial

This study is testing if closely managing heart health in young adults aged 30-50 can slow down the buildup of artery plaque compared to regular care.

Quick facts

• Phase: PHASE3
• Study type: Interventional
• Enrollment: 1600 (estimated)
• Ages: 30 Years to 50 Years
• Sex: All
• Sponsor: Icahn School of Medicine at Mount Sinai (other)
• Drugs / interventions: radiation
• Locations: 1 site (New York, New York)
• Trial ID: NCT06494501 on ClinicalTrials.gov

What this trial studies

This trial evaluates whether strict control of cardiovascular risk factors in young adults aged 30-50 without known cardiovascular disease can reduce the progression of atherosclerosis compared to usual care. It involves a randomized controlled design with 1,600 participants who will be assigned to either an active treatment group receiving Inclisiran or a control group. The study aims to demonstrate the benefits of early LDL-C lowering therapies, which could shift current prevention strategies in the medical community. The primary endpoint is the reduction in total atherosclerosis burden, a surrogate for symptomatic cardiovascular disease.

Who should consider this trial

Good fit: Ideal candidates are healthy males and females aged 30 to 50 with elevated LDL-C and evidence of subclinical atherosclerosis.

Not a fit: Patients with a history of coronary artery disease, cerebrovascular disease, or peripheral artery disease will not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could significantly lower the risk of cardiovascular events in young adults by addressing atherosclerosis early.

How similar studies have performed: Other studies have shown the significance of early intervention in atherosclerosis, but this specific approach is novel and untested in this age group.

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.

Where this trial is running

New York, New York

• Mount Sinai Fuster Heart Hospital — New York, New York, United States (RECRUITING)

Study contacts

• Principal investigator: Valentin Fuster, MD, PhD — Icahn School of Medicine at Mount Sinai
• Study coordinator: Malick Waqas

Conditions: Atherosclerotic Cardiovascular Disease