Inclisiran for Cardiovascular Disease Prevention

Recruiting at 1034 trial locations

Overseen By Seth J Baum

Age: 18+

Sex: Any

Travel: May Be Covered

Trial Phase: Phase 3

Sponsor: Novartis Pharmaceuticals

Must be taking: Lipid lowering

Must not be taking: PCSK9 inhibitors

Disqualifiers: ASCVD, Revascularization, 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: 1

Duration: Up to 75 months

14013 Participants Needed

Trial Summary

Do I have to stop taking my current medications for this trial?

The trial does not specify if you need to stop taking your current medications. However, if you are on lipid-lowering therapy, you must stay on a stable dose for at least 4 weeks before the screening and throughout the study.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on lipid-lowering therapy, you must have been on a stable dose for at least 4 weeks before the screening and be willing to continue it throughout the study.

What data supports the idea that Inclisiran for Cardiovascular Disease Prevention is an effective drug?

The available research shows that Inclisiran is effective in reducing the risk of heart attacks by 32% in patients with atherosclerotic cardiovascular disease or those at high risk. However, it does not significantly reduce the risk of strokes or other major heart-related events. While it is generally safe, it can cause mild to moderate reactions at the injection site. More studies are needed to confirm these findings. ^{1 2 3 4 5}

What data supports the effectiveness of the drug Inclisiran for cardiovascular disease prevention?

Research shows that Inclisiran can reduce the risk of heart attacks by 32% in patients with atherosclerotic cardiovascular disease, but it does not significantly lower the risk of strokes or major cardiovascular events. It is generally safe, with mild to moderate reactions at the injection site being the most common side effect. ^{1 6 7 8 9}

What safety data exists for Inclisiran in cardiovascular disease prevention?

The provided research does not contain safety data for Inclisiran or its other names such as Inclisiran sodium, Leqvio, ALN-PCSsc, ALN-60212, Placebo, Control, or Dummy Treatment. The studies focus on other drugs like celecoxib, VA694, diclofenac, and parecoxib sodium, primarily concerning their cardiovascular and gastrointestinal safety. ^{10 11 12 13 14}

Is Inclisiran sodium, also known as Leqvio, a promising drug for preventing cardiovascular disease?

The information provided does not include any details about Inclisiran sodium or its effectiveness in preventing cardiovascular disease. Therefore, we cannot determine if it is a promising drug based on the given data. ^{2 15 16 17 18}

How is the drug Inclisiran unique for cardiovascular disease prevention?

Inclisiran is unique because it works by targeting a specific molecule in the liver to lower cholesterol levels, and it is administered as an injection only a few times a year, unlike other cholesterol-lowering drugs that are taken daily. ^{2 15 16 17 18}

What is the purpose of this trial?

This trial tests whether inclisiran injections can prevent serious heart problems in high-risk adults who haven't had a major heart event yet by lowering their cholesterol levels. Inclisiran is a long-acting treatment that significantly lowers cholesterol.

Research Team

Novartis Pharmaceuticals

Principal Investigator

Novartis Pharmaceuticals

Eligibility Criteria

This trial is for adults aged 40-80 with high cholesterol and at increased risk of a first major cardiovascular event, but who haven't had one before. They should have an intermediate 10-year heart disease risk score with additional risk factors. Pregnant women, nursing mothers, or those in another study can't participate.

Inclusion Criteria

My heart disease risk for the next 10 years is between 7.5% and 20%, and I have at least two risk factors.

I am between 40 and 80 years old.

You have a higher risk of experiencing a first major cardiovascular event and have not had one before.

Exclusion Criteria

Are you currently participating in another research study?

I have had a major heart or blood vessel event.

You are currently pregnant or breastfeeding.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive inclisiran sodium 300 mg or placebo administered subcutaneously on Day 1, Day 90, and every 6 months thereafter

Up to 75 months

Visits on Day 1, Day 90, and every 6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Minimum of 3 years

Treatment Details

Interventions

• Inclisiran sodium
• Placebo

Trial Overview The trial tests if Inclisiran sodium (a drug given by injection) can prevent serious heart-related events when administered initially, after three months, and then every six months compared to a placebo. The goal is to see if it reduces the occurrence of events like heart attacks or strokes.

Participant Groups

Group I: Inclisiran sodium 300mg Experimental Treatment 1 Intervention

Inclisiran sodium 300 mg in 1.5 mL solution for injection (subcutaneous) in pre-filled syringe. Randomized in a 1:1 ratio with matching placebo

Group II: Placebo Placebo Group 1 Intervention

Matching placebo in 1.5ml pre-filled syringe. Randomized in a 1:1 ratio with Inclisiran.

Inclisiran sodium is already approved in European Union, United States, China for the following indications:

Approved in European Union as Leqvio for:

• Primary hypercholesterolemia (heterozygous familial and non-familial)
• Mixed dyslipidemia

Approved in United States as Leqvio for:

• Heterozygous familial hypercholesterolemia (HeFH)
• Clinical atherosclerotic cardiovascular disease (ASCVD)
• Primary hypercholesterolemia

Approved in China as Leqvio for:

• Primary hypercholesterolemia (heterozygous familial and non-familial)
• Mixed dyslipidemia

Who Is Running the Clinical Trial?

Novartis Pharmaceuticals

Lead Sponsor

Trials

2,963

Recruited

4,275,000+

Founded

1996

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Gleevec, Cosentyx, Entresto, Kisqali

Dr. Vas Narasimhan

Novartis Pharmaceuticals

Chief Executive Officer since 2018

MD from Harvard Medical School

Dr. Shreeram Aradhye

Novartis Pharmaceuticals

Chief Medical Officer since 2021

MD

Findings from Research

Inclisiran significantly reduces the risk of myocardial infarction (MI) by 32% in patients with atherosclerotic cardiovascular disease (ASCVD), based on a meta-analysis of three randomized controlled trials involving 3,713 patients.

However, inclisiran does not show a significant effect on reducing the risk of stroke or major cardiovascular events, and while its safety profile is similar to placebo, it is associated with a higher incidence of mild to moderate injection-site reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of inclisiran in stroke or cerebrovascular disease prevention: a systematic review and meta-analysis of randomized controlled trials. Luo, M., Liu, Y., Xu, X., et al.[2023]

In a study of 734 patients with mild-to-moderate essential hypertension, valsartan demonstrated similar effectiveness in reducing diastolic blood pressure compared to lisinopril, with both treatments significantly lowering blood pressure compared to placebo.

Valsartan was associated with a lower incidence of cough (1.1%) compared to lisinopril (8%), suggesting it may be a better tolerated option for patients sensitive to this side effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Valsartan, a new angiotensin II antagonist for the treatment of essential hypertension: efficacy, tolerability and safety compared to an angiotensin-converting enzyme inhibitor, lisinopril. Black, HR., Graff, A., Shute, D., et al.[2022]

In a study involving 48 healthy volunteers, candesartan cilexetil demonstrated the highest pharmacological potency among angiotensin II receptor antagonists, effectively lowering diastolic blood pressure with a calculated K(i)-dose of 6 mg at 24 hours.

All tested angiotensin II receptor antagonists showed dose-dependent effects on blood pressure, and their K(i)-doses were within the recommended clinical ranges for treating hypertension, indicating their potential efficacy in managing this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The pharmacological potency of various AT(1) antagonists assessed by Schild regression technique in man. Belz, GG., Breithaupt-Grögler, K., Butzer, R., et al.[2018]

Quinaprilat, administered in single and multiple intravenous doses ranging from 0.5 to 10 mg, significantly improved heart function by increasing cardiac index and reducing pressures in the heart and lungs in patients with severe congestive heart failure.

The treatment was well-tolerated with no significant adverse effects, and it effectively lowered levels of angiotensin II and aldosterone while increasing plasma renin activity, demonstrating its mechanism as an ACE inhibitor.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hemodynamic and hormonal effects of quinaprilat in patients with congestive heart failure. Mitrovic, V., Mudra, H., Bonzel, T., et al.[2014]

Analysis of registration files for 13 cardiovascular drugs revealed that half of the 146 double-blind phase-III clinical trials utilized active comparator drugs, indicating a robust approach to evaluating drug efficacy against existing treatments.

The study highlighted inconsistencies in trial reporting, such as varying dosing schemes and the use of only placebo or active controls, suggesting a need for standardized reporting to improve the clarity of European Public Assessment Reports.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative trials in registration files of cardiovascular drugs: comparator drugs and dosing schemes. Wieringa, NF., Vos, R., de Graeff, PA.[2019]

Celecoxib shows a lower risk of cardiovascular events and all-cause mortality compared to non-selective non-steroidal anti-inflammatory drugs (NSAIDs), with risk ratios of 0.89 and 0.81 respectively, based on a meta-analysis of 21 trials involving rheumatoid arthritis and osteoarthritis patients.

The study suggests that celecoxib is relatively safe for cardiovascular health in these patients, but its safety in individuals taking aspirin or those with existing cardiovascular diseases remains uncertain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiovascular safety of celecoxib in rheumatoid arthritis and osteoarthritis patients: A systematic review and meta-analysis. Cheng, BR., Chen, JQ., Zhang, XW., et al.[2022]

VA694, a new NO-releasing COX2 inhibitor, shows promise in reducing cardiovascular risks associated with traditional COX2 inhibitors by releasing nitric oxide, which can improve vascular function.

In a study with young spontaneously hypertensive rats, chronic administration of VA694 slowed the development of hypertension and improved coronary flow, suggesting it may offer both anti-inflammatory and cardiovascular benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The novel anti-inflammatory agent VA694, endowed with both NO-releasing and COX2-selective inhibiting properties, exhibits NO-mediated positive effects on blood pressure, coronary flow and endothelium in an experimental model of hypertension and endothelial dysfunction. Martelli, A., Testai, L., Anzini, M., et al.[2016]

Between 2011 and 2014, the initiation of diclofenac prescriptions decreased by about 30% among both male and female patients in Germany, indicating a positive response to European risk minimization measures.

Despite the decrease in overall diclofenac use, the proportion of new patients with contraindications (such as heart failure and ischemic heart disease) remained high, suggesting ongoing safety concerns and the need for further research to enhance prescribing practices.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Are prescribers not aware of cardiovascular contraindications for diclofenac? A claims data analysis. Scholle, O., Kollhorst, B., Haug, U.[2020]

In a study involving 7297 patients aged 60 and over, switching from non-selective NSAIDs to celecoxib did not result in a higher rate of cardiovascular events, indicating similar safety profiles for both treatments over a median follow-up of 3 years.

The study found that while gastrointestinal and hematological adverse reactions were more common with non-selective NSAIDs, there was no significant cardiovascular advantage to switching to celecoxib, as the risk of serious events remained low and comparable between the two groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized trial of switching from prescribed non-selective non-steroidal anti-inflammatory drugs to prescribed celecoxib: the Standard care vs. Celecoxib Outcome Trial (SCOT). MacDonald, TM., Hawkey, CJ., Ford, I., et al.[2022]

In a study involving 123 healthy adults, parecoxib sodium (40 mg twice daily for 7 days) showed a superior gastrointestinal safety profile compared to ketorolac (30 mg four times daily for 5 days), with no subjects developing ulcers or significant erosions.

While 28% of subjects taking ketorolac developed ulcers and 48% had significant erosions, parecoxib sodium's safety was comparable to placebo, indicating it may be a safer alternative for pain management without gastrointestinal risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Parecoxib sodium demonstrates gastrointestinal safety comparable to placebo in healthy subjects. Harris, SI., Stoltz, RR., LeComte, D., et al.[2019]

The combination of perindopril and lercanidipine significantly lowered blood pressure more effectively than either medication alone in patients with mild essential hypertension, with notable improvements seen as early as 4 weeks into treatment.

Patients receiving the combination therapy experienced fewer adverse events compared to those on monotherapy, indicating a better safety profile for the combination treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety evaluation of perindopril-lercanidipine combined therapy in patients with mild essential hypertension. Yang, Z.[2019]

In a 1-year study involving 411 hypertensive patients with left ventricular hypertrophy, indapamide sustained release (SR) 1.5 mg significantly reduced left ventricular mass index (LVMI) by an average of -8.4 g/m2, while enalapril 20 mg showed no significant reduction.

Indapamide SR was more effective than enalapril in reducing LVMI by -6.5 g/m2, and it consistently reduced wall thickness over the treatment period, unlike enalapril, whose effects diminished after 6 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Regression of left ventricular hypertrophy in hypertensive patients treated with indapamide SR 1.5 mg versus enalapril 20 mg: the LIVE study. Gosse, P., Sheridan, DJ., Zannad, F., et al.[2019]

In a study of 281 adults with mild-to-moderate primary hypertension, both lercanidipine and felodipine significantly reduced diastolic blood pressure after 6 weeks of treatment, demonstrating their efficacy in managing hypertension.

Lercanidipine was found to be a safe treatment option, with a similar incidence of adverse events compared to felodipine, indicating that it can be effectively used for blood pressure control without unexpected side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lercanidipine hydrochloride versus felodipine sustained-release for mild-to-moderate hypertension: a multi-center, randomized clinical trial. Wu, Y., Xu, M., Wang, H., et al.[2018]

Sodium Tanshinone II A Sulfonate Injection (STS) significantly improves treatment outcomes for unstable angina pectoris (UAP) when used alongside Western medicine, as shown in a meta-analysis of 17 randomized controlled trials involving 1,372 patients.

While STS enhances effectiveness by improving total effective rates and reducing inflammatory markers, it is associated with a higher occurrence of adverse drug reactions compared to standard treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sodium Tanshinone II A Sulfonate Injection as Adjuvant Treatment for Unstable Angina Pectoris: A Meta-Analysis of 17 Randomized Controlled Trials. Tan, D., Wu, JR., Zhang, XM., et al.[2022]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Efficacy and safety of inclisiran in stroke or cerebrovascular disease prevention: a systematic review and meta-analysis of randomized controlled trials. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Valsartan, a new angiotensin II antagonist for the treatment of essential hypertension: efficacy, tolerability and safety compared to an angiotensin-converting enzyme inhibitor, lisinopril. [2022]

3. England pubmed.ncbi.nlm.nih.gov

The pharmacological potency of various AT(1) antagonists assessed by Schild regression technique in man. [2018]

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

Hemodynamic and hormonal effects of quinaprilat in patients with congestive heart failure. [2014]

5. Germany pubmed.ncbi.nlm.nih.gov

Comparative trials in registration files of cardiovascular drugs: comparator drugs and dosing schemes. [2019]

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

Patient preferences for a polypill for the prevention of cardiovascular diseases. [2018]

7. Spain pubmed.ncbi.nlm.nih.gov

Consensus document for the use of the Polypill in the secondary prevention of cardiovascular disease. [2018]

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

The value of the polypill in cardiovascular disease: an Italian multidisciplinary Delphi panel consensus. [2023]

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

Maximizing therapeutic envelope for prevention of cardiovascular disease: role of polypill. [2014]

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

Cardiovascular safety of celecoxib in rheumatoid arthritis and osteoarthritis patients: A systematic review and meta-analysis. [2022]

11. Netherlands pubmed.ncbi.nlm.nih.gov

The novel anti-inflammatory agent VA694, endowed with both NO-releasing and COX2-selective inhibiting properties, exhibits NO-mediated positive effects on blood pressure, coronary flow and endothelium in an experimental model of hypertension and endothelial dysfunction. [2016]

12. England pubmed.ncbi.nlm.nih.gov

Are prescribers not aware of cardiovascular contraindications for diclofenac? A claims data analysis. [2020]

13. England pubmed.ncbi.nlm.nih.gov

Randomized trial of switching from prescribed non-selective non-steroidal anti-inflammatory drugs to prescribed celecoxib: the Standard care vs. Celecoxib Outcome Trial (SCOT). [2022]

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

Parecoxib sodium demonstrates gastrointestinal safety comparable to placebo in healthy subjects. [2019]

15. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety evaluation of perindopril-lercanidipine combined therapy in patients with mild essential hypertension. [2019]

16. Netherlands pubmed.ncbi.nlm.nih.gov

Regression of left ventricular hypertrophy in hypertensive patients treated with indapamide SR 1.5 mg versus enalapril 20 mg: the LIVE study. [2019]

17. England pubmed.ncbi.nlm.nih.gov

Lercanidipine hydrochloride versus felodipine sustained-release for mild-to-moderate hypertension: a multi-center, randomized clinical trial. [2018]

18. China pubmed.ncbi.nlm.nih.gov

Sodium Tanshinone II A Sulfonate Injection as Adjuvant Treatment for Unstable Angina Pectoris: A Meta-Analysis of 17 Randomized Controlled Trials. [2022]