The Prevent Coronary Artery Disease Trial

NCT06494501 | Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: STUDY-23-01528
• Study Type: interventional
• Target: 1,600
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Atherosclerotic Cardiovascular Disease

Outcome Measures

Primary Outcomes (1)

• Change in atherosclerotic plaque burden from baseline

  Change in atherosclerotic plaque burden at 2.5 years and the last year of follow up from baseline as measured by the 3D vascular ultrasound. Atherosclerotic plaque burden is amount of plaque in the arteries.

  Baseline, 2.5 years and 5 years after randomization

Secondary Outcomes (1)

• Change in Number of participants with Cardiovascular Disease (CVD)

  Baseline and 5 years after randomization

Study Arms (2)

Inclisiran

EXPERIMENTAL

Participants in this arm will receive the study drug (inclisiran, for 5 years). Specific measures will be implemented to achieve the following goals: LDL-C \<55 mg/dl; blood pressure \<130/80 mmHg; and HbA1c \<6.5%. Diet and lifestyle recommendations will be recommended to all patients as a first step. Follow-up will occur every 2 months until goals are achieved. If the goal is not achieved, the subsequent recommendation will be implemented. Pharmacologic treatment may be implemented as early as the first visit at the discretion of the physician. * Product Name: inclisiran * Active ingredient: inclisiran sodium * Dosage Form: Solution for Injection * Unit Dose Inclisiran sodium 300 mg/1.5 mL vial (equivalent to 284 mg inclisiran) * Route of Administration: SC use * Physical Description: Clear, colorless to pale yellow solution essentially free of particulates

Drug: Inclisiran

Control Group

NO INTERVENTION

Participants in this group will receive guideline directed medical treatment, according to American Heart Association/American College of Cardiology guidelines. These recommendations will be provided to the primary care physicians to be followed, according to standards of care. Follow-up visits will occur every 6 months, although patients might be seen more often according to their provider´s criteria.

Interventions

Inclisiran DRUG

Subjects will be administered a single subcutaneous injection of 284 mg inclisiran for injection at predefined time points.

Also known as: Leqvio

Inclisiran

Eligibility Criteria

• Age: 30 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Icahn School of Medicine at Mount Sinai: lead

Study Sites (1)

Mount Sinai Fuster Heart Hospital

New York, New York, 10029, United States

RECRUITING

MeSH Terms

Conditions

Atherosclerosis

Interventions

ALN-PCS

Condition Hierarchy (Ancestors)

Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases

Study Officials

• Valentin Fuster, MD, PhD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Malick Waqas

CONTACT

646-939-7532; precadteam@mountsinai.org

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chairman Mount Sinai Fuster Heart Hospital

Study Record Dates

• First Submitted: June 23, 2024
• First Posted: July 10, 2024
• Study Start: September 12, 2024
• Primary Completion (Estimated): June 30, 2032
• Study Completion (Estimated): June 30, 2032
• Last Updated: April 29, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)