PRE-EMPT: Prospective RandomizEd Evaluation and Management of Premature aTherosclerosis (PRE-EMPT)

Prospective RandomizEd Evaluation and Management of Premature aTherosclerosis

Heart disease is the leading cause of death for men, women, and people of most racial and ethnic groups in the United States. This clinical trial will test if screening and early treatment of mild heart disease works.

PRE-EMPT will screen individuals at low 10-year risk of heart disease with heart disease risk factors to identify those who already have early cholesterol build up, also called "plaque", in their heart arteries. It consists of two phases:

1. A Screening Study - Participants will be assessed for plaque by one or both of these scans.

   • Coronary Artery Calcium (CAC) Scan: A CT scan that looks for calcium or plaque in heart arteries.
   • Coronary CT Angiography (CCTA) Scan: A CT scan that uses contrast dye to create detailed 3D pictures of heart arteries to look for plaque.

2. A Treatment Trial (approximately 1,500 participants) - Based on the results of the CCTA, participants may be randomized into a two-year trial to test medications aimed at reducing or stabilizing plaque. Participants will have a 1 in 4 chance of receiving only placebo, and a 3 in 4 chance of receiving at least one active medication. Participants will take two pills once a day-either both active medications, one active and one placebo, or both placebos.

   • Rosuvastatin 20 mg: a cholesterol-lowering medicine
   • Colchicine 0.5 mg: a medication that lowers inflammation

Everyone in the trial will be given information and advice on heart-healthy diet and lifestyle.

Participants will have up to two in-person visits for the screening study, then phone visits for the Treatment Trial at the beginning, 3 months, 12 months and 24 months when they will also have an in-person visit for a CCTA Scan. Participants will have blood drawn using an at-home collection device mailed to their home at the beginning, 3 months, and end of the study.

Study Overview

• Status: Not yet recruiting
• Conditions: Premature Atherosclerosis; Coronary Artery Disease Progression; Prevention & Control; Coronary Artery Disease Risk Factors Multiple
• Intervention / Treatment: Drug: Rosuvastatin 20 Mg Oral Tablet; Drug: Placebo; Drug: Colchicine 0.5 MG Oral Tablet Once Daily

Detailed Description

The PRE-EMPT trial will be a 2x2 factorial, double-masked, placebo-controlled randomized trial of the effects of high-intensity statin and low-dose colchicine, alone and in combination, on CCTA-defined Non-Calcified Coronary Plaque (NCCP) volume at 2 years. Participants found through the screening study with CAC 1-99, or through the known plaque pathway, will be eligible for the trial if they have NCCP without severe stenosis or any other exclusion criteria. Study drug will be delivered directly to participants' homes, lab samples will be self-collected at home, and all study visits will be virtual except the imaging visits (up to 3 over 2 years). The only in-person study activities will be the CAC scan, if applicable, and CCTA at baseline and 2 years. The investigators anticipate that this approach will be attractive to middle-aged, busy individuals who are otherwise healthy and asymptomatic. Importantly, all participants in PRE-EMPT will receive an mHealth lifestyle intervention designed to support behavioral modification, ensuring that all individuals benefit from evidence-based strategies for cardiovascular risk reduction.

• Study Type: Interventional
• Enrollment (Estimated): 1500
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: PRE-EMPT Email; Phone Number: 919-309-5544; Email: PREEMPT@duke.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Women aged 40-60 years; Men aged 30-50 years
2. Willing and able to provide informed consent and comply with study procedures
3. Smart phone user
4. Use of highly effective contraception by females with reproductive potential.
5. CAC score 1-99 in the screening study or entry through the known plaque pathway (with mild CAC or CAC<100 if known; elevated CAC on baseline CCTA is not exclusionary in the known plaque arm)
6. Diagnostic baseline CCTA with NCPV ≥10 mm3 as assessed by the central core lab

Exclusion Criteria:

1. Clinical diagnosis of ASCVD including coronary artery disease (CAD), peripheral arterial disease (PAD) or cerebrovascular disease (CeVD)
2. Current symptoms thought to be from CAD
3. PREVENT ASCVD 10-year risk ≥5% (if known)
4. Diabetes Mellitus (DM) as defined by any of the following: DM diagnosis in the medical record or HbA1C of 6.5% or greater. (if known)
5. LDL-C ≥190mg/dL (most recent, if known)
6. HIV (if known)
7. Severe liver disease or untreated Hepatitis C infection (if known)
8. Pregnancy, lactation or intending to become pregnant during the study period of 2 years
9. eGFR <45mL/min/1.73m2 (if known)
10. AST or ALT >1.5x the upper limit of normal (if known)
11. BMI>40kg/m2 or unable to have a CCTA scan for any reason
12. Allergy to iodinated intravenous contrast or other contraindication to CCTA
13. Current or previous use of lipid lowering therapy or colchicine
14. Known allergic reactions or sensitivity to the study intervention(s), including known intolerance or contraindication(s) to statin or colchicine, or long-term use of medications that are contraindicated with colchicine or rosuvastatin.
15. Systemic cancer undergoing active treatment
16. PREVENT ASCVD 10-year risk ≥5%
17. eGFR <45 ml/min/1.73m2 per baseline labs, (2021 CKD-EPI equation will be used if multiple options are available)
18. Hemoglobin A1c ≥6.5% per baseline labs
19. LDL-C ≥190mg/dL per baseline labs
20. Severe proximal coronary artery stenosis as determined by the central core lab (≥50% left main or ≥70% proximal major coronary artery stenosis)
21. Known contraindication to follow-up CCTA (e.g., new IV contrast allergy discovered during the baseline CCTA)
22. Individuals who are excluded based on any of these factors will be notified as to the reason for exclusion and encouraged to follow-up locally to address this medical issue with their treating physician.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: rosuvastatin 20mg plus colchicine-matched placebo; statin plus placebo (two pills once daily)	Drug: Rosuvastatin 20 Mg Oral Tablet; Statin; Other Names: Crestor; Drug: Placebo; Placebo, non-active, drug-matched
Experimental: colchicine 0.5mg plus rosuvastatin-matched placebo; anti-inflammatory plus placebo (two pills once daily)	Drug: Placebo; Placebo, non-active, drug-matched; Drug: Colchicine 0.5 MG Oral Tablet Once Daily; Anti-inflammatory; Other Names: Lodoco
Experimental: rosuvastatin 20mg plus colchicine 0.5mg; statin plus anti-inflammatory (two pills once daily)	Drug: Rosuvastatin 20 Mg Oral Tablet; Statin; Other Names: Crestor; Drug: Colchicine 0.5 MG Oral Tablet Once Daily; Anti-inflammatory; Other Names: Lodoco
Placebo Comparator: placebo plus placebo; Placebo and placebo (two pills once daily)	Drug: Placebo; Placebo, non-active, drug-matched

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Non-calcified plaque volume (NCPV) on CCTA at 2 years, adjusted for baseline NCPV.	Plaque volume in mm3 in each group	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with Drug Discontinuation	Drug Tolerability outcome	Up to 2 years
Overall drug treatment adherence	Number of days on study drugs	Up to 2 years
Safety events of special interest	Number of safety events of special interest per group	Up to 2 years
Total plaque volume	Plaque volume in mm3 per group	Up to 2 years
Low-attenuation plaque volume	Low attenuated plaque volume in mm3 per group	Up to 2 years
Calcified plaque volume	Calcified plaque volume in mm3 per group	Up to 2 years
Number of participants with stenosis	Number of participants with stenosis per group	Up to 2 years
Segment involvement score	Average score per group	Up to 2 years
Number of participants with qualitative calcified, partially calcified and non-calcified plaque composition	Number of participants with each plaque composition description per group	Up to 2 years
Number of participants with High-risk plaque features (positive remodeling, spotty calcium, napkin ring sign)	Number of participants with each plaque feature (high-risk) per group	Up to 2 years
Change in LDL-C (low-density lipoprotein cholesterol)		Baseline to 2 years
Change in non-HDL-C (high-density lipoprotein cholesterol)		Baseline to 2 years

Collaborators and Investigators

• Sponsor: Duke University
• Collaborators: Johns Hopkins University; Massachusetts General Hospital; National Heart, Lung, and Blood Institute (NHLBI); University of North Carolina, Chapel Hill

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): July 1, 2031
• Study Completion (Estimated): July 1, 2031

Study Registration Dates

• First Submitted: November 14, 2025
• First Submitted That Met QC Criteria: November 14, 2025
• First Posted (Actual): November 18, 2025

Study Record Updates

• Last Update Posted (Actual): February 27, 2026
• Last Update Submitted That Met QC Criteria: February 25, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: coronary artery calcium; Prevention; Heart Disease Prevention; Family History of Heart Disease; At risk for heart disease; non-calcified coronary plaque
• Additional Relevant MeSH Terms: Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pharmaceutical Preparations; Dosage Forms; Hydrocarbons; Alkaloids; Amides; Pyrimidines; Hydrocarbons, Halogenated; Sulfonamides; Sulfones; Fluorobenzenes; Hydrocarbons, Fluorinated; Rosuvastatin Calcium; Colchicine; Tablets
• Other Study ID Numbers: Pro00118744; UG3HL181434 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes