Statin + Colchicine for Coronary Artery Disease

(PROACT 2 Trial)

Overseen By Fangzhou Cheng

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

Trial Summary

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 data supports the effectiveness of the drug combination of Colchicine and Rosuvastatin for Coronary Artery Disease?

Research shows that Rosuvastatin, a type of statin, is very effective at lowering bad cholesterol (LDL-C), which can help reduce the risk of heart disease. This suggests that using Rosuvastatin in combination with other treatments might be beneficial for heart health. ^{1 2 3 4 5}

Is the combination of statin and colchicine safe for treating coronary artery disease?

Rosuvastatin, a type of statin, is generally safe with mostly acceptable side effects, but rare serious side effects like ischaemic colitis (inflammation of the colon due to reduced blood flow) have been reported. There is no specific safety data available for the combination of statin and colchicine in the provided research. ^{2 4 6 7 8}

What makes the drug Rosuvastatin unique for coronary artery disease?

Rosuvastatin is unique because it is a potent statin that not only lowers bad cholesterol (LDL) more effectively than other statins but also has anti-inflammatory effects, which can be beneficial for coronary artery disease. Its ability to significantly reduce LDL cholesterol and increase good cholesterol (HDL) makes it a promising option for patients who do not achieve their cholesterol goals with other treatments. ^{1 2 3 5 9}

What is the purpose of this trial?

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.

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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]

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 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 (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 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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

A new statin: a new standard. [2023]

2. India pubmed.ncbi.nlm.nih.gov

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

3. Switzerland 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. [2017]

4. England 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. [2019]

5. New Zealand 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. [2015]

6. England pubmed.ncbi.nlm.nih.gov

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

7. United States pubmed.ncbi.nlm.nih.gov

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

8. England pubmed.ncbi.nlm.nih.gov

Adverse drug reaction: rosuvastatin as a cause for ischaemic colitis in a 64-year-old woman. [2021]

9. England pubmed.ncbi.nlm.nih.gov

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