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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether adding a statin, specifically rosuvastatin, to the usual blood thinner treatment can help prevent future blood clots and reduce vein damage in people with recent blood clots in the legs or lungs. Although typically used to lower cholesterol, rosuvastatin is being tested for its potential benefits in managing blood clots. Participants will receive either rosuvastatin or a placebo (a harmless pill with no active ingredients) to compare the effects. Ideal candidates for this trial include individuals diagnosed with a blood clot in the leg or lung within the past month who are not already taking statins and do not have conditions like diabetes or heart disease that typically require statins. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that rosuvastatin, the medication under study, has been well-tolerated in past trials. One study found that rosuvastatin reduced the risk of blood clots by about 47% compared to a placebo. This suggests the drug not only lowers cholesterol but might also reduce the risk of blood clots.

Another study indicated that rosuvastatin decreased the chance of developing symptoms of blood clots. These findings suggest that rosuvastatin is safe and could help prevent blood clots. Additionally, rosuvastatin is already approved in Canada for lowering cholesterol, which further supports its safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about using rosuvastatin for blood clots because it takes a different approach than the usual anticoagulant treatments like warfarin or heparin. While most blood clot treatments work by thinning the blood to prevent new clots, rosuvastatin, a statin, primarily lowers cholesterol levels but also appears to have anti-inflammatory and stabilizing effects on blood vessel walls. This dual action could potentially reduce the risk of clot formation in a novel way, offering a complementary strategy to traditional anticoagulants. By targeting inflammation and cholesterol, rosuvastatin may provide a broader protective effect against clot-related complications.

What evidence suggests that rosuvastatin might be an effective treatment for blood clots?

Research has shown that rosuvastatin, a medication often used to lower cholesterol, might also help prevent blood clots. One study found that people taking rosuvastatin had a 47% lower risk of developing venous thromboembolism (VTE). Another study indicated that rosuvastatin can decrease certain substances in the blood that aid clot formation. Additionally, rosuvastatin reduced the production of thrombin, which is crucial for clot formation. In this trial, participants in the experimental arm will receive rosuvastatin to evaluate its effectiveness in preventing blood clots, while participants in the control arm will receive a placebo. These findings suggest that adding rosuvastatin to blood thinner treatments might offer extra protection against new blood clots. ^{1 3 4 6 7}

Who Is on the Research Team?

Aurélien Delluc, M.D. Ph. D.

Principal Investigator

Ottawa Hospital Research Institute

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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 (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 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, 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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8859624/

Rosuvastatin for the prevention of venous thromboembolism In this individual participant data meta-analysis, rosuvastatin reduced the risk of VTE by 47% across a pooled primary CVD prevention population with a broad ...

2. ashpublications.org ashpublications.org/bloodadvances/article/9/17/4472/537626/The-efficacy-of-rosuvastatin-to-reduce-circulating

The efficacy of rosuvastatin to reduce circulating tissue factor ... The primary outcome was to evaluate whether rosuvastatin in combination with enoxaparin lowers levels of circulating TF+EV compared with ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6850636/

Rosuvastatin use reduces thrombin generation potential in ... Endogenous thrombin potential and peak were decreased by 10% and 5% with rosuvastatin therapy. These results provide basis for trials on the efficacy of statins ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S2475037925003280

The role of statins in mitigating venous thromboembolism ... The STAtins Reduce Thrombophilia (START) trial found that among patients with a prior VTE, rosuvastatin reduced thrombin generation potential and led to an ...

5. nejm.org nejm.org/doi/full/10.1056/NEJMoa0900241

A Randomized Trial of Rosuvastatin in the Prevention ... In this trial of apparently healthy persons, rosuvastatin significantly reduced the occurrence of symptomatic venous thromboembolism.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10500145/

Risk of Venous Thromboembolism with Statins Compared with a placebo, rosuvastatin reduced the VTE risk by around 45% and fenofibrate increased the risk by 65%. Conclusion: Rosuvastatin is significantly ...

7. academic.oup.com academic.oup.com/cardiovascres/article-abstract/118/3/897/6168423

Rosuvastatin for the prevention of venous thromboembolism Rosuvastatin is associated with a 47% proportional reduction in the risk of VTE, and its effect is consistent both in the presence or absence of ...