Statin + Colchicine for Coronary Artery Disease

(PROACT 2 Trial)

Overseen By Roukoz Abou-Karam, MD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Massachusetts General Hospital

Must not be taking: LDL-lowering, Anti-inflammatory, CY2P inhibitors

Disqualifiers: Cardiovascular disease, Liver disease, Pregnancy, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 52 weeks

200 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests how a combination of two medications, rosuvastatin (a statin) and colchicine, affects heart health in individuals with a high genetic risk for coronary artery disease, a condition where the heart's blood vessels narrow or become blocked. Researchers aim to determine if these treatments slow down or alter the makeup of plaque in the arteries. Participants will be divided into groups receiving either the combination of both drugs, one drug with a placebo, or just a placebo. Suitable candidates have visible plaque in their heart arteries but less than 70% blockage and have not been diagnosed with coronary artery disease. As a Phase 4 trial, this study involves treatments already FDA-approved and proven effective, aiming to understand how they can benefit more patients.

Will I have to stop taking my current medications?

The trial requires that you stop taking any LDL cholesterol lowering or anti-inflammatory medications, including colchicine, before participating.

What is the safety track record for these treatments?

Research has shown that both rosuvastatin and colchicine have been tested for safety in people. Rosuvastatin, a common medication for lowering cholesterol, is usually well-tolerated. Studies indicate it can improve symptoms in those with heart disease and high cholesterol. Possible side effects include muscle pain or liver problems, particularly for individuals who consume alcohol heavily or have liver issues.

Colchicine is often used to reduce inflammation and has been shown to lower the risk of major heart problems by about 25%. It has been studied in people with heart disease and, while it doesn't reduce the risk of death, it helps with inflammation. Some individuals might experience stomach upset or diarrhea.

The combination of these two treatments has also been studied. A review of research found that the heart health benefits of colchicine generally outweigh any potential risks. This suggests that using them together could be safe for most people, though side effects may vary. Always consult a healthcare provider for personalized advice. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about combining rosuvastatin and colchicine for coronary artery disease because it targets inflammation and cholesterol simultaneously. Unlike standard treatments that primarily focus on lowering cholesterol, this combination brings colchicine into the mix, which is known for its anti-inflammatory properties. By addressing both inflammation and cholesterol, this dual approach could potentially offer better protection against heart attacks and other coronary events. This treatment is promising because it may enhance patient outcomes by tackling two key contributors to coronary artery disease.

What evidence suggests that this trial's treatments could be effective for coronary artery disease?

Research has shown that rosuvastatin can lower the risk of heart attacks, strokes, and other heart-related problems in people with coronary artery disease (CAD) by reducing bad cholesterol, a key factor in heart disease. Colchicine, meanwhile, reduces inflammation and can lower the risk of major heart issues by about 25% in people with CAD. In this trial, participants in Group D will receive both rosuvastatin and colchicine, potentially increasing these benefits, as rosuvastatin targets cholesterol and colchicine addresses inflammation. However, taking these drugs together might raise the risk of muscle problems for some individuals. Overall, both treatments have proven effective in managing CAD, especially when combined. ^{1 2 4 5 6}

Are You a Good Fit for This Trial?

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.

Inclusion Criteria

I am between 40 and 75 years old and can give my consent.

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

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

Exclusion Criteria

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

You have had a strong allergic reaction to iodinated contrast, colchicine, or statins in the past.

I cannot hold my breath for 10 seconds.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomized into four groups to receive either placebo, rosuvastatin, colchicine, or both rosuvastatin and colchicine daily

52 weeks

Regular visits for monitoring and assessment

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Colchicine
• Rosuvastatin

Trial Overview 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.

How Is the Trial Designed?

Group I: Group D Active Control 2 Interventions

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

Group II: Group B Active Control 2 Interventions

Participants will receive rosuvastatin 20mg daily and placebo daily

Group III: Group C Active Control 2 Interventions

Participants will receive colchicine 0.6mg daily and placebo daily

Group IV: Group A Placebo Group 1 Intervention

Participants will receive placebo daily

Rosuvastatin is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Crestor for:

• High cholesterol
• Hyperlipoproteinemia
• Prevention of cardiovascular disease

Approved in European Union as Crestor for:

• Hypercholesterolemia
• Mixed dyslipidemia
• Homozygous familial hypercholesterolemia

Approved in Canada as Crestor for:

• Hypercholesterolemia
• Mixed dyslipidemia
• Prevention of cardiovascular disease

Approved in Japan as Crestor for:

• Hypercholesterolemia
• Familial hypercholesterolemia

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Published Research Related to This Trial

Rosuvastatin (Crestor) is more effective than other statins in lowering low-density lipoprotein cholesterol (LDL-C), showing greater reductions across doses of 5-40 mg/day, and also increases high-density lipoprotein cholesterol while significantly reducing triglycerides.

In clinical trials, rosuvastatin was well tolerated with a low incidence of adverse events, demonstrating a safety profile similar to other statins, although long-term safety and effectiveness in preventing coronary events have not been established.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rosuvastatin: a high-potency HMG-CoA reductase inhibitor. Lopez, LM.[2019]

Rosuvastatin, a new statin, has shown significant dose-dependent reductions in LDL cholesterol (LDL-C) ranging from 34% to 65% compared to placebo, indicating its efficacy in lowering cholesterol levels in hypercholesterolemic patients.

In Phase III studies, rosuvastatin was found to be more effective than other commonly used statins like atorvastatin, pravastatin, and simvastatin in improving lipid profiles, suggesting it could be a superior option for patients who struggle to reach target LDL-C levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A new statin: a new standard. Olsson, AG.[2023]

In the JUPITER trial, rosuvastatin significantly reduced the occurrence of major cardiovascular events in healthy individuals aged ≥60 years (women) or ≥50 years (men) with normal LDL-C levels but elevated hsCRP levels, demonstrating its efficacy in primary prevention of cardiovascular disease.

Rosuvastatin was well tolerated, with most side effects being mild to moderate, and it effectively lowered both LDL-C and hsCRP levels, although the exact mechanism of its benefits remains unclear.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rosuvastatin: a review of its use in the prevention of cardiovascular disease in apparently healthy women or men with normal LDL-C levels and elevated hsCRP levels. Carter, NJ.[2015]

Rosuvastatin is a highly effective statin that can significantly lower LDL cholesterol levels by 52-63% and increase HDL cholesterol levels by up to 14%, making it superior to other statins like atorvastatin and simvastatin in improving cholesterol profiles.

It has a favorable safety profile, with minimal drug interactions due to its low metabolism by the CYP 450 enzyme system, and is well tolerated by patients, making it a reliable option for managing hypercholesterolemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rosuvastatin: a new inhibitor of HMG-coA reductase for the treatment of dyslipidemia. Rosenson, RS.[2022]

In a study of 502 patients with primary hypercholesterolemia, rosuvastatin (5 mg and 10 mg) significantly reduced LDL cholesterol levels by 42% and 49%, respectively, outperforming pravastatin and simvastatin, which reduced LDL-C by 28% and 37%.

Rosuvastatin 10 mg achieved National Cholesterol Education Program (NCEP) treatment goals in 87% of patients, demonstrating its superior efficacy compared to pravastatin (53%) and simvastatin (64%), while all treatments were well tolerated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rosuvastatin demonstrates greater reduction of low-density lipoprotein cholesterol compared with pravastatin and simvastatin in hypercholesterolaemic patients: a randomized, double-blind study. Paoletti, R., Fahmy, M., Mahla, G., et al.[2019]

Rosuvastatin is a potent statin that significantly reduces LDL cholesterol by 52-63% at doses of 10-40 mg, outperforming other statins like atorvastatin and simvastatin in lowering LDL levels.

It is well tolerated and has a safety profile similar to other statins, making it a suitable option for patients with dyslipidemia, including those with hypertriglyceridemia or diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rosuvastatin--a highly effective new 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor: review of clinical trial data at 10-40 mg doses in dyslipidemic patients. Schuster, H.[2017]

Rosuvastatin is a powerful statin that effectively lowers total cholesterol, LDL cholesterol, triglycerides, and apolipoprotein B, potentially achieving better results than other statins, making it a promising option for treating hyperlipidaemia.

It is well tolerated with a low risk of liver or muscle toxicity, and its once-daily dosing and minimal drug interactions make it a convenient choice for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical rationale for rosuvastatin, a potent new HMG-CoA reductase inhibitor. Hanefeld, M.[2015]

Rosuvastatin calcium has a unique safety profile similar to other statins but offers different efficacy benefits, making it a valuable option for lowering LDL cholesterol and improving coronary heart disease outcomes.

The GALAXY program and the JUPITER study provide extensive evidence supporting rosuvastatin's effectiveness and safety across diverse patient populations, including those with traditional and emerging risk factors for coronary heart disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rosuvastatin: a highly potent statin for the prevention and management of coronary artery disease. Kapur, NK.[2015]

Rosuvastatin, a commonly prescribed medication for high cholesterol, is generally safe but can lead to rare and serious side effects, such as ischaemic colitis.

In a case study of a 64-year-old woman, ischaemic colitis was diagnosed after starting rosuvastatin, and her symptoms resolved completely after discontinuing the drug, highlighting the need for awareness of this potential adverse reaction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse drug reaction: rosuvastatin as a cause for ischaemic colitis in a 64-year-old woman. Tan, J., Pretorius, CF., Flanagan, PV., et al.[2021]

Citations

1. nature.com nature.com/articles/s41569-025-01230-2

Colchicine in patients with cardiovascular disease This analysis demonstrated that colchicine treatment, compared with medical therapy alone, reduces the rate of major cardiac events by 25%.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/41019029/

Efficacy and safety of colchicine in patients with coronary ... Conclusion: Colchicine does not reduce the relative risk of all-cause and cardiovascular death in patients with CAD. However, it can reduce the ...

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa2021372

Colchicine in Patients with Chronic Coronary Disease Evidence from a recent trial has shown that the antiinflammatory effects of colchicine reduce the risk of cardiovascular events in patients with recent ...

4. ccjm.org ccjm.org/content/92/10/609

Low-dose colchicine for management of coronary artery ... A total of 451 primary outcome events were reported, and colchicine was associated with a 31% lower relative risk of the primary end point ( ...

5. jacc.org jacc.org/doi/10.1016/j.jacc.2023.05.055

Low-Dose Colchicine for Secondary Prevention of ... Low-dose colchicine (0.5 mg/d orally) has been shown to safely lower major adverse cardiovascular events by 31% among those with stable atherosclerosis and by ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S2666602225001132

Efficacy and safety of colchicine in patients with coronary ... Our results demonstrate no significant reduction in all-cause or cardiovascular mortality with colchicine. This is an important finding as it ...