Statins for Blood Clots

(SAVER Trial)

Recruiting at 17 trial locations

Overseen By Jennifer Brinkhurst

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Ottawa Hospital Research Institute

Must be taking: Anticoagulants

Must not be taking: Statins, Cyclosporine, Atazanavir

Disqualifiers: Diabetes, Stroke, Liver disease, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 60 months

2700 Participants Needed

Trial Summary

What is the purpose of this trial?

The standard or usual treatment for patients diagnosed with deep vein thrombosis or pulmonary embolism is treatment with blood thinners (called anticoagulants). While treatment of blood clots with blood thinners is effective, some research has shown that adding a statin (medication used to lower cholesterol) may give extra protection. It is thought that statins can improve how cells along the walls of the vein control inflammation, which can prevent new blood clots from forming. The medication in this study, rosuvastatin, is approved in Canada for use as a cholesterol-lowering medication. The use of rosuvastatin in this study is considered investigational. This means that Health Canada has not approved the use of rosuvastatin as a treatment for blood clots. However, it has been approved for use in this research study. The purpose of this study is to examine if adding a statin (rosuvastatin) to the usual blood thinner treatment will decrease the risk of another blood clot forming. The investigators also hope to discover if taking a statin reduces damage to your veins. To do this, some of the participants in this study will get rosuvastatin and others will receive a placebo (a substance that looks like the study rosuvastatin but does not have any active or medicinal ingredients). The placebo in this study is not intended to have any effect on your blood clot. A placebo is used to make the results of the study more reliable.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are already taking a statin or certain other medications like cyclosporine or atazanavir/ritonavir.

What data supports the effectiveness of the drug Rosuvastatin (Crestor) for preventing blood clots?

Rosuvastatin (Crestor) has been shown to reduce the risk of major cardiovascular events, including venous thromboembolism (a type of blood clot), in patients with elevated hsCRP levels, as demonstrated in the JUPITER trial. ^{1 2 3 4 5}

Is rosuvastatin (Crestor) generally safe for humans?

Rosuvastatin (Crestor) is generally well tolerated and has a safety profile similar to other statins, meaning it is considered safe for use in humans when used as directed. ^{2 6 7 8 9}

How does the drug rosuvastatin differ from other treatments for blood clots?

Rosuvastatin is unique because it not only lowers cholesterol but also has anti-inflammatory effects, which may help in preventing blood clots. Unlike other statins, it is highly potent and selective for liver cells, reducing the risk of interactions with other drugs. ^{1 2 8 9 10}

Research Team

Aurélien Delluc, M.D. Ph. D.

Principal Investigator

Ottawa Hospital Research Institute

Eligibility Criteria

This trial is for adults who've had a recent deep vein thrombosis or pulmonary embolism. It's not for those with liver disease, severe kidney issues, on certain medications like cyclosporine, pregnant/breastfeeding women, under 18s, or anyone already taking statins. Participants must be willing to use contraception if of childbearing potential.

Inclusion Criteria

I have a recent diagnosis of a significant blood clot in my leg or lung.

Exclusion Criteria

You are allergic to statins.

I have a known liver disease.

I cannot take rosuvastatin due to health reasons.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either rosuvastatin or placebo daily for the duration of the study

Up to 60 months

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of recurrent VTE and post-thrombotic syndrome

Up to 60 months

Treatment Details

Interventions

• Placebo Oral Tablet
• Rosuvastatin Calcium

Trial Overview The study tests whether adding rosuvastatin (a cholesterol-lowering drug) to standard blood thinner treatment can prevent new blood clots and reduce vein damage in patients with blood clots. Some participants will receive rosuvastatin while others get a placebo tablet that has no active ingredients.

Participant Groups

Group I: Rosuvastatin Experimental Treatment 1 Intervention

Participants randomized to the experimental arm will take one rosuvastatin 20 mg tablet by mouth every day for the duration of their participation in the study.

Group II: Placebo Placebo Group 1 Intervention

Participants randomized to the control arm will take one placebo tablet by mouth every day for the duration of their participation in the study.

Who Is Running the Clinical Trial?

Ottawa Hospital Research Institute

Lead Sponsor

Trials

585

Recruited

3,283,000+

Findings from Research

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 is an effective statin that significantly improves lipid profiles in patients with dyslipidemias, outperforming other statins like atorvastatin, pravastatin, and simvastatin in achieving LDL-C goals after 12 weeks of treatment.

The treatment is generally well tolerated, with low incidences of serious side effects, such as myopathy and elevated CPK levels, making rosuvastatin a safe first-line option for managing cholesterol in both low- and high-risk patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rosuvastatin: a review of its use in the management of dyslipidemia. Scott, LJ., Curran, MP., Figgitt, DP.[2018]

In a study involving 516 hypercholesterolemic patients, rosuvastatin (5 mg and 10 mg) significantly reduced LDL cholesterol levels more than atorvastatin (10 mg), achieving reductions of -40% and -43% compared to -35% for atorvastatin.

Rosuvastatin also led to greater increases in HDL cholesterol and better achievement rates for LDL cholesterol goals set by major health organizations, while both rosuvastatin and atorvastatin were well tolerated by patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of effects on low-density lipoprotein cholesterol and high-density lipoprotein cholesterol with rosuvastatin versus atorvastatin in patients with type IIa or IIb hypercholesterolemia. Davidson, M., Ma, P., Stein, EA., et al.[2019]

Rosuvastatin, a potent statin, not only significantly lowers LDL-cholesterol levels but also raises HDL-cholesterol levels, which is beneficial for heart health.

Clinical trials have shown that rosuvastatin positively impacts the progression of atherosclerosis and improves cardiovascular outcomes, supporting its use in preventing cardiovascular disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical experience with rosuvastatin in the management of hyperlipidemia and the reduction of cardiovascular risk. Nicholls, SJ., Uno, K., Kataoka, Y.[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, currently in phase III clinical trials, shows promise in significantly lowering total cholesterol and LDL cholesterol levels in patients with high cholesterol, potentially more effectively than other statins.

However, there is not enough evidence to assess the safety of rosuvastatin or its impact on heart-related health outcomes, indicating that further research is needed to fully understand its benefits and risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rosuvastatin: do we need another statin? Ho, C.[2010]

Rosuvastatin is a highly potent statin that effectively inhibits cholesterol synthesis, showing up to a 65% reduction in LDL cholesterol in hypercholesterolemic patients during early-phase studies.

The drug selectively targets liver cells with minimal uptake in nonhepatic tissues, and it has low potential for metabolic interactions, making it a safe option for lipid-lowering therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimizing the pharmacology of statins: characteristics of rosuvastatin. Chapman, MJ., McTaggart, F.[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]

In two studies involving 206 moderately hypercholesterolemic patients, rosuvastatin demonstrated significant dose-dependent reductions in LDL cholesterol, with decreases ranging from 34% at 1 mg to 65% at 80 mg after 6 weeks of treatment.

Rosuvastatin was well tolerated, with no significant increases in liver enzymes or muscle damage markers, indicating a favorable safety profile alongside its efficacy in lowering cholesterol.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of rosuvastatin on low-density lipoprotein cholesterol in patients with hypercholesterolemia. Olsson, AG., Pears, J., McKellar, J., et al.[2022]

References

1. 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]

2. 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]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Rosuvastatin: a review of its use in the management of dyslipidemia. [2018]

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

Comparison of effects on low-density lipoprotein cholesterol and high-density lipoprotein cholesterol with rosuvastatin versus atorvastatin in patients with type IIa or IIb hypercholesterolemia. [2019]

5. England pubmed.ncbi.nlm.nih.gov

Clinical experience with rosuvastatin in the management of hyperlipidemia and the reduction of cardiovascular risk. [2015]

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

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

7. Canada pubmed.ncbi.nlm.nih.gov

Rosuvastatin: do we need another statin? [2010]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Optimizing the pharmacology of statins: characteristics of rosuvastatin. [2019]

9. 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]

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

Effect of rosuvastatin on low-density lipoprotein cholesterol in patients with hypercholesterolemia. [2022]