What side effects are associated with this type of intervention?

High-intensity statins, used to lower LDL cholesterol, can cause muscle-related side effects like myopathy and, rarely, rhabdomyolysis, as well as elevated liver enzymes and new-onset diabetes. Low-dose colchicine, used to reduce inflammation, can cause gastrointestinal issues such as diarrhea, nausea, and abdominal pain, with a potential but not significantly higher risk of myopathy when combined with statins.

What prior FDA approvals exist?

High-intensity statins, including atorvastatin and rosuvastatin, have been FDA-approved for the treatment of Coronary Artery Disease (CAD) due to their efficacy in inhibiting HMG-CoA reductase, which significantly lowers LDL cholesterol levels and reduces cardiovascular risk. Additionally, colchicine, known for its anti-inflammatory properties, has been explored for CAD management, although its use in this context is less common and not as widely approved. These treatments aim to address both lipid levels and inflammation, key factors in the progression of CAD.

What other types of research exist?

Promising novel alternatives for CAD patients include PCSK9 inhibitors (e.g., evolocumab, inclisiran) which significantly lower LDL cholesterol, and RNA-based therapies targeting PCSK9, which have shown durable LDL-C reduction. These alternatives offer new mechanisms of action and potential benefits over traditional statins and colchicine.

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HMG-CoA Reductase Inhibitor

Statin + Colchicine for Coronary Artery Disease (PROACT 2 Trial)

Q: What is the mechanism of action of this treatment?

High-intensity statins inhibit HMG-CoA reductase, reducing LDL cholesterol levels and thereby decreasing the formation of atherosclerotic plaques, which are critical in preventing coronary artery blockages and heart attacks. Low-dose colchicine reduces inflammation by inhibiting microtubule polymerization, which helps stabilize atherosclerotic plaques and prevent their rupture, thus reducing the risk of acute coronary events. These mechanisms are vital for managing and preventing the progression of Coronary Artery Disease.

Phase 4

Recruiting

Research Sponsored by Massachusetts General Hospital

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

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

Must not have

Female patient who is pregnant, or breast-feeding or is considering becoming pregnant during the study

Participant unable to hold breath for 10 seconds

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 1 year

Awards & highlights

Drug Has Already Been Approved

Pivotal Trial

Summary

This trial is testing a cholesterol-lowering drug (rosuvastatin), an anti-inflammatory drug (colchicine), and their combination in people with a genetic risk for heart disease. The goal is to see if these treatments can reduce or prevent plaque buildup in arteries. Rosuvastatin lowers bad cholesterol, while colchicine reduces inflammation, which together might be more effective. Rosuvastatin is one of the most potent drugs available for reducing bad cholesterol levels, which enables more high-risk patients to achieve their lipid goals.

Who is the study for?

This trial is for men and women aged 40-75 with a high genetic risk for coronary artery disease, who have early-stage plaque buildup in their arteries seen on a heart scan but no severe blockage. They must not have liver or severe kidney disease, allergies to the drugs being tested, be taking certain other medications, be pregnant or breastfeeding, extremely overweight, or have a history of heart problems.

What is being tested?

The study tests if high-dose statins (Rosuvastatin), low-dose Colchicine, or their combination can slow down or change the makeup of early-stage artery plaque in people at high genetic risk for heart disease. Participants are randomly assigned to get one of these treatments or a placebo without knowing which one they're getting.

What are the potential side effects?

Possible side effects include muscle pain and weakness from Rosuvastatin; diarrhea, nausea and potential blood disorders from Colchicine; plus general risks like allergic reactions. The exact side effects will vary by individual.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My clinical test shows I have a high risk for coronary artery disease.

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I have early-stage artery disease visible on a heart scan, but it's not severely blocking my arteries.

Select...

I have a high genetic risk for heart artery disease.

Select...

I have early-stage artery blockage visible on a heart scan.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I am pregnant, breastfeeding, or might become pregnant during the study.

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I cannot hold my breath for 10 seconds.

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My kidney function is reduced, with low filtration rates or high creatinine.

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I have a history of heart or blood vessel disease.

Select...

I am unable to understand and give consent for treatment.

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I am not taking strong CY2P inhibitors like ketoconazole.

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My BMI is 40 or higher.

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I am currently on medication to lower my LDL cholesterol or for inflammation.

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I have liver disease or my recent liver tests are much higher than normal.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 1 year

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~1 year

This trial's timeline: 3 weeks for screening, Varies for treatment, and 1 year for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Change in total non-calcified plaque volume from baseline to one year

Secondary study objectives

Change in C-reactive protein (CRP) from baseline to one year

Change in Interleukin-6 and Interleukin-1 beta (IL-1ß) from baseline to one year

Change in calcium score from baseline to one year

+6 more

Awards & Highlights

Drug Has Already Been Approved

The FDA has already approved this drug, and is just seeking more data.

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

4Treatment groups

Active Control

Placebo Group

Group I: Group DActive Control2 Interventions

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

Group II: Group BActive Control2 Interventions

Participants will receive rosuvastatin 20mg daily and placebo daily

Group III: Group CActive Control2 Interventions

Participants will receive colchicine 0.6mg daily and placebo daily

Group IV: Group APlacebo Group1 Intervention

Participants will receive placebo daily

0 / 13Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

High-intensity statins inhibit HMG-CoA reductase, reducing LDL cholesterol levels and thereby decreasing the formation of atherosclerotic plaques, which are critical in preventing coronary artery blockages and heart attacks. Low-dose colchicine reduces inflammation by inhibiting microtubule polymerization, which helps stabilize atherosclerotic plaques and prevent their rupture, thus reducing the risk of acute coronary events. These mechanisms are vital for managing and preventing the progression of Coronary Artery Disease.

Simultaneous low-density lipoprotein-C lowering and high-density lipoprotein-C elevation for optimum cardiovascular disease prevention with various drug classes, and their combinations: a meta-analysis of 23 randomized lipid trials.