Statin + Colchicine for Coronary Artery Disease
(PROACT 2 Trial)
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 4
Recruiting
Sponsor: Massachusetts General Hospital
Must not be taking: LDL-lowering, Anti-inflammatory, CY2P inhibitors
Disqualifiers: Cardiovascular disease, Liver disease, Pregnancy, others
Prior Safety Data
Approved in 5 Jurisdictions
Trial Summary
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.
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.
12345Is 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.
24678What 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.
12359Eligibility 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.
+2 more
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.
+7 more
Trial 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
Participant Groups
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.
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
Rosuvastatin is already approved in United States, European Union, Canada, Japan, Australia 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
🇦🇺 Approved in Australia as Crestor for:
- Hypercholesterolemia
- Mixed dyslipidemia
- Prevention of cardiovascular disease
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Massachusetts General HospitalBoston, MA
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Who Is Running the Clinical Trial?
Massachusetts General HospitalLead Sponsor
National Heart, Lung, and Blood Institute (NHLBI)Collaborator
References
A new statin: a new standard. [2023]Numerous studies have demonstrated that treatments designed to reduce low-density lipoprotein cholesterol (LDL-C) can reduce the risk of coronary heart disease (CHD) events in the setting of either primary or secondary prevention. The rationale for aggressive lowering of LDL-C, supported by large observational studies, is the concept that no threshold exists below which reductions fail to provide additional benefit. The statins are widely considered first-line therapy for preventing CHD events because these agents yield the greatest reductions in LDL-C. However, many patients do not achieve target LDL-C levels with the currently available statins. Newer, more effective statins may permit the benefits of aggressive LDL-C reduction to be extended to larger numbers of patients. A novel, highly efficacious statin, rosuvastatin (Crestor, AstraZeneca group of companies), is currently undergoing clinical investigation. Dose-ranging studies in hypercholesterolemic patients have shdwn that rosuvastatin produces significant, dose-dependent decreases in LDL-C when compared with placebo. Reductions have ranged from 34% at a dose of 1 mg/day to 65% at 80 mg/day. This agent has been found to be well tolerated across the range of doses studied. Phase III studies indicate that rosuvastatin is more effective than atorvastatin, pravastatin, and simvastatin in improving the atherogenic lipid profiles of hypercholesterolemic patients, and more effective than atorvastatin in improving the atherogenic lipid profiles of patients with heterozygous familial hypercholesterolemia. Overall, these findings suggest that rosuvastatin is a promising new medication for the treatment of dyslipidemias.
Clinical rationale for rosuvastatin, a potent new HMG-CoA reductase inhibitor. [2015]Coronary heart disease (CHD) is the leading cause of death worldwide, and effective treatment of hyperlipidaemia can prevent development of CHD and significantly reduce the risk for cardiovascular events and mortality in this disease. The advent of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) has revolutionised the treatment of hyperlipidaemia, but many patients receiving these drugs still do not achieve their therapeutic goals. Rosuvastatin (Crestor; formerly ZD4522) is a new, potent and long-lasting inhibitor of HMG-CoA reductase that is highly selective for hepatocytes. Its pharmacokinetics permit once-daily dosing, and a lack of oxidative hepatic metabolism results in a reduced potential for drug-drug interactions. Preliminary clinical results indicate that it produces rapid dose-related reductions in total cholesterol, low-density lipoprotein cholesterol, triglycerides, and apolipoprotein B that may exceed those achieved with other currently available statins. Increases in high-density lipoprotein cholesterol have also been observed. Rosuvastatin is also well tolerated, with no evidence of either hepato- or myotoxicity. It is hoped that new agents such as rosuvastatin may help to reduce the high global morbidity, mortality and associated costs of CHD and related vascular disorders.
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]Rosuvastatin (Crestor; licensed to AstraZeneca, Macclesfield, UK from Shionogi, Osaka, Japan) is a new statin with pharmacologic characteristics that translate into selectivity of effect in hepatic cells and enhanced potency in 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibition. It is approved for use at doses of 10-40 mg once daily to reduce low-density lipoprotein (LDL) cholesterol, increase high-density lipoprotein (HDL) cholesterol and improve other lipid measures in dyslipidemic patients. In a dose-ranging study in mild/moderate hypercholesterolemia, rosuvastatin reduced LDL cholesterol by 52-63% at 10-40 mg. Rosuvastatin 10 mg reduces LDL cholesterol significantly more than atorvastatin 10 mg, simvastatin 10-40 mg and pravastatin 10-40 mg, and enables significantly more patients to achieve National Cholesterol Education Program and Joint European Societies LDL cholesterol goals compared with each of these statins. Rosuvastatin also produces marked elevations in HDL cholesterol and maintains this effect across the dose range. Rosuvastatin favorably modifies triglycerides, LDL cholesterol and other lipid measures in patients with hypertriglyceridemia or mixed dyslipidemia, including diabetic patients, and may constitute a monotherapy option for many such patients. Rosuvastatin is well tolerated when used alone or in combination, exhibiting a safety profile similar to that of other available statins. Rosuvastatin offers considerable advantages for use in routine clinical practice.
Rosuvastatin demonstrates greater reduction of low-density lipoprotein cholesterol compared with pravastatin and simvastatin in hypercholesterolaemic patients: a randomized, double-blind study. [2019]Rosuvastatin (Crestor), a new, highly efficacious statin, has demonstrated dose-dependent low-density lipoprotein cholesterol (LDL-C) reductions of up to 65% in a dose-ranging programme with doses of 1 to 80 mg.
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]Rosuvastatin (Crestor®) is an HMG-CoA reductase inhibitor (statin) that has both lipid-lowering and anti-inflammatory effects. The drug has various indications in the US, including the primary prevention of cardiovascular disease (CVD) in patients with no clinical evidence of coronary heart disease who are at increased risk of CVD based on their age, a high-sensitivity C-reactive protein (hsCRP) level of ≥2 mg/L, and at least one other CVD risk factor. The efficacy of rosuvastatin in apparently healthy women (aged ≥60 years) or men (aged ≥50 years) with normal low-density lipoprotein cholesterol (LDL-C) levels and elevated hsCRP levels was demonstrated in the large, randomized, double-blind, multinational, JUPITER trial. Relative to placebo, rosuvastatin 20 mg once daily for a median follow-up of 1.9 years significantly reduced the occurrence of first major cardiovascular events in this trial (primary endpoint). A between-group difference in favor of rosuvastatin was also demonstrated for various other endpoints, including overall deaths and the nonatherothrombotic endpoint of venous thromboembolism. Rosuvastatin remained more effective than placebo when primary endpoint results were stratified according to various baseline factors, including in patient subgroups thought to be at low risk of CVD. In addition, rosuvastatin was associated with reductions in LDL-C and hsCRP levels, and these reductions appeared to occur independently of each other. The greatest clinical benefit was observed in rosuvastatin recipients achieving an LDL-C level of
Rosuvastatin: a highly potent statin for the prevention and management of coronary artery disease. [2015]Since the identification of a fungal metabolite that inhibits HMG-CoA reductase in 1976, statins have emerged rapidly as the global leader in pharmacotherapeutics designed to lower low-density lipoprotein cholesterol (LDL-C). In conjunction, practice guidelines have recommended increasingly aggressive measures to improve coronary heart disease (CHD) outcomes by lowering LDL-C. By virtue of unique chemical characteristics, enhanced binding thermodynamics and limited cytochrome P450 3A4 metabolism, rosuvastatin calcium has a safety profile in line with currently marketed statins, but a different efficacy profile. Mirroring this chemical profile, the GALAXY program represents a comprehensive evaluation of the efficacy, safety and cost-effectiveness of rosuvastatin in individuals representing various clinical diagnoses, pathophysiological states and ethnicities. Also results from the Justification for the Use of statins in Primary prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) study could provide further evidence for the use of rosuvastatin in individuals with traditional and emerging CHD risk factors, such as an elevated high sensitivity C-reactive protein level. This review will provide a comprehensive evaluation of the chemistry, clinical efficacy, safety and tolerability of rosuvastatin, and discuss the future role in the management of CHD and atherosclerosis.
Rosuvastatin: a high-potency HMG-CoA reductase inhibitor. [2019]To summarize the relevant pharmacologic, clinical, and safety data regarding rosuvastatin (Crestor--AstraZeneca), the most recently marketed 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor approved for the treatment of dyslipidemia.
Adverse drug reaction: rosuvastatin as a cause for ischaemic colitis in a 64-year-old woman. [2021]Rosuvastatin (Crestor, AstraZeneca) is a commonly used drug for managing hypercholesterolaemia. It is a very safe medication with mostly acceptable side effects. Rare but serious side effects are not well known. A 64-year-old woman presented with bloody diarrhoea after starting rosuvastatin for hypercholesterolaemia. Stool microscopy and culture ruled out infective causes. Abdominal CT scan revealed normal calibre celiac axis and superior mesenteric artery. Colonoscopic biopsy revealed ischaemic colitis as the final histological diagnosis. The patient is in complete remission after ceasing the medication. Rosuvastatin causing ischaemic colitis should be considered a rare but serious adverse drug reaction.
Rosuvastatin: a new inhibitor of HMG-coA reductase for the treatment of dyslipidemia. [2022]Rosuvastatin (Crestor, AstraZeneca) is a synthetic statin that represents an advance on the pharmacologic and clinical properties of other agents in this class. Relative to other statins, rosuvastatin possesses a greater number of binding interactions with HMG-CoA reductase and has a high affinity for the active site of the enzyme. Rosuvastatin is relatively hydrophilic and is selectively taken up by, and active in, hepatic cells. Rosuvastatin has the longest terminal half-life of the statins and is only minimally metabolized by the cytochrome P450 (CYP 450) enzyme system with no significant involvement of the 3A4 enzyme. Consistent with this finding is the absence of clinically significant drug interactions between rosuvastatin and other drugs known to inhibit CYP 450 enzymes. In patients with hypercholesterolemia, rosuvastatin 10-40 mg has been shown to reduce low-density lipoprotein cholesterol (LDL-C) levels by 52-63%, as well as increase high-density lipoprotein cholesterol (HDL-C) levels by up to 14% and reduce triglycerides (TG) by up to 28%. Studies have shown that rosuvastatin is superior to atorvastatin, simvastatin and pravastatin in reducing LDL-C and favorably modifying other components of the atherogenic lipid profile. The significant decreases in LDL-C with rosuvastatin treatment should help to improve attainment of lipid goals and reduce the requirement for dose titration. In addition, the effects of rosuvastatin on HDL-C and TG levels will be of benefit in treating patients with abnormalities such as mixed dyslipidemia and the metabolic syndrome. Rosuvastatin is well tolerated, with a safety profile comparable with that of other currently available statins.