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

Duke University

Status and phase: Begins enrollment in 3 months; Phase 3

Conditions: Premature Atherosclerosis; Prevention & Control; Coronary Artery Disease Progression; Coronary Artery Disease Risk Factors Multiple

Treatments: Drug: Placebo; Drug: Colchicine 0.5 MG Oral Tablet Once Daily; Drug: Rosuvastatin 20 Mg Oral Tablet

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT07232069

UG3HL181434 (U.S. NIH Grant/Contract)

Pro00118744

Details and patient eligibility

About

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.

Full 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.

Enrollment: 1,500 estimated patients

Sex: All

Ages: 30 to 60 years old

Volunteers: No Healthy Volunteers

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 Diagnosis (MI, stroke, arterial revascularization) or current symptoms thought to be from coronary artery disease
2. PREVENT ASCVD 10-year risk ≥5% (if known)
3. Diabetes Mellitus (DM) as defined by any of the following: new DM diagnosis in the medical record or HbA1C of 6.5% or greater. (if known)
4. LDL-C ≥190mg/dL (most recent, if known)
5. HIV (if known)
6. Severe liver disease or untreated Hepatitis C infection (if known)
7. Pregnancy, lactation or intending to become pregnant during the study period of 2 years
8. eGFR <45mL/min/1.73m2 (if known)
9. AST or ALT >1.5x the upper limit of normal (if known)
10. BMI>40kg/m2
11. Allergy to iodinated intravenous contrast or other contraindication to CCTA
12. Current or previous use of lipid lowering therapy or colchicine
13. 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.
14. Systemic cancer undergoing active treatment
15. PREVENT ASCVD 10-year risk ≥5%
16. eGFR <45 ml/min/1.73m2 per baseline labs
17. Hemoglobin A1c ≥6.5% per baseline labs
18. LDL-C ≥190mg/dL per baseline labs
19. Severe proximal coronary artery stenosis as determined by the central core lab
20. Known contraindication to follow-up CCTA (e.g., new IV contrast allergy discovered during the baseline CCTA)

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Factorial Assignment

Masking: Quadruple Blind

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1,500 participants in 4 patient groups, including a placebo group

rosuvastatin 20mg plus colchicine-matched placebo

Experimental group

Description:

statin plus placebo (two pills once daily)

Treatment:

Drug: Rosuvastatin 20 Mg Oral Tablet

Drug: Placebo

colchicine 0.5mg plus rosuvastatin-matched placebo

Experimental group

Description:

anti-inflammatory plus placebo (two pills once daily)

Treatment:

Drug: Colchicine 0.5 MG Oral Tablet Once Daily

Drug: Placebo

rosuvastatin 20mg plus colchicine 0.5mg

Experimental group

Description:

statin plus anti-inflammatory (two pills once daily)

Treatment:

Drug: Rosuvastatin 20 Mg Oral Tablet

Drug: Colchicine 0.5 MG Oral Tablet Once Daily

placebo plus placebo

Placebo Comparator group

Description:

Placebo and placebo (two pills once daily)

Treatment:

Drug: Placebo