Polygenic Risk-based Detection of Subclinical Coronary Atherosclerosis and Intervention With Statin and Colchicine (PROACT 2)

Mass General Brigham

Status and phase: Enrolling; Phase 4

Conditions: Coronary Artery Disease

Treatments: Drug: Colchicine; Drug: Rosuvastatin; Drug: Placebo

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT05850091

2023P000945

Details and patient eligibility

About

The goal of this double-blind randomized controlled trial is to determine how treatment with high intensity statin, low-dose colchicine, and their combination modulates progression and composition of coronary atherosclerosis in individuals with high polygenic risk for coronary artery disease.

Full description

The main question PROACT 2 aims to answer is whether and how single or dual targeting of cholesterol-lowering and inflammation modulates coronary plaque in individuals with high polygenic risk and subclinical coronary atherosclerosis.

This is a double-blind randomized controlled trial of 200 individuals with high polygenic risk for coronary artery disease and subclinical plaque on coronary computed tomography angiography. Participants will be randomized into four equal treatment groups: group A receiving a placebo daily, group B receiving rosuvastatin 20mg daily, group C receiving colchicine 0.6mg daily, and group D receiving both rosuvastatin 20mg daily and colchicine 0.6mg daily. The primary outcome is change in total non-calcified plaque volume on coronary computed tomography angiography from baseline to one year. Multiple secondary plaque imaging and biomarker outcomes will be explored in this pilot mechanistic trial.

Enrollment: 200 estimated patients

Sex: All

Ages: 40 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Males and females between 40 and 75 years of age capable and willing to provide informed consent
• Participant has high CAD PRS as defined on a clinical test
• Participant with subclinical atherosclerosis defined as plaque visible on CCTA and causing <70% luminal stenosis

Exclusion criteria

• Participant with a history of cardiovascular disease, defined by a diagnosis of coronary artery disease, peripheral artery disease, or cerebrovascular disease
• Participant with a history of Liver disease (cirrhosis, active hepatitis, or severe hepatic disease) or any of the following recent lab results and determined to be non-transient: alanine aminotransferase greater than 3 times the upper limit of normal or total bilirubin greater than 2 times the upper limit of normal (unless due to Gilbert syndrome)
• Participant with estimated glomerular filtration rate <60 mL/min/1.73 m2 or creatinine greater than 2 times the upper limit of normal
• Patient with history of an allergic reaction or significant sensitivity to iodinated contrast, colchicine, or statins
• Patient currently taking LDL cholesterol lowering or anti- inflammatory medications including colchicine
• Participants requiring regular drugs known to be potent CY2P inhibitors (eg. ketoconazole, clarithromycin)
• Female patient who is pregnant, or breast-feeding or is considering becoming pregnant during the study
• Participant with BMI ≥ 40 kg/m2
• Participant unable to provide informed consent
• Participant unable to hold breath for 10 seconds

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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200 participants in 4 patient groups, including a placebo group

Group A

Placebo Comparator group

Description:

Participants will receive placebo daily

Treatment:

Drug: Placebo

Group B

Active Comparator group

Description:

Participants will receive rosuvastatin 20mg daily and placebo daily

Treatment:

Drug: Placebo

Drug: Rosuvastatin

Group C

Active Comparator group

Description:

Participants will receive colchicine 0.6mg daily and placebo daily

Treatment:

Drug: Placebo

Drug: Colchicine

Group D

Active Comparator group

Description:

Participants will receive rosuvastatin 20mg daily and colchicine 0.6mg daily

Treatment:

Drug: Rosuvastatin

Drug: Colchicine