Inclisiran for Cardiovascular Disease Prevention
Recruiting in Palo Alto (17 mi)
+1034 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Waitlist Available
Sponsor: Novartis Pharmaceuticals
Pivotal Trial (Near Approval)
Prior Safety Data
Trial Summary
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.
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.
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.
12345What 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.
678910Is 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.
211121314Eligibility 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.
+1 more
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.
Participant Groups
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.
2Treatment groups
Experimental Treatment
Placebo Group
Group I: Inclisiran sodium 300mgExperimental Treatment1 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: PlaceboPlacebo Group1 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Tustin Research SiteTustin, CA
Novartis Investigative SiteOwensboro, KY
Novartis Investigative SiteStamford, CT
Novartis Investigative SiteSpringfield, OH
More Trial Locations
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Who Is Running the Clinical Trial?
Novartis PharmaceuticalsLead Sponsor
References
Efficacy and safety of inclisiran in stroke or cerebrovascular disease prevention: a systematic review and meta-analysis of randomized controlled trials. [2023]Aims: As the impact of inclisiran in stroke prevention in atherosclerotic cardiovascular disease (ASCVD) patients or those at high risk of ASCVD is still unclear, we conducted a systematic review and meta-analysis of randomized controlled trials (RCT) to quantify the effectiveness of inclisiran in stroke prevention in these patients. Methods: Literature research was conducted in four electronic databases (PubMed, EMBASE, Web of Science, CENTRAL) and two clinical trials registers (ClinicalTrials.gov, WHO ICTRP) from the inception of the study to 17 October 2022, and was updated by the end of the study on 5 January 2023. Two authors independently screened the studies, extracted the data, and assessed the bias. The risk of bias was assessed using the Cochrane risk-of-bias tool for randomized trials (RoB 2). The intervention effect was estimated by calculating risk ratio (RR), weighted mean difference (WMD), and 95% confidence interval (CI) with R 4.0.5. Sensitivity analysis by changing meta-analysis model was also performed to test the robustness of the pooled results. If this was not possible, a descriptive analysis was conducted. Results: Four RCTs (n = 3,713 patients) were rated as high-risk bias. Meta-analysis of three RCTs (ORION-9, ORION-10, and ORION-11) showed that inclisiran reduced myocardial infarction (MI) risk by 32% (RR = 0.68, 95%CI = 0.48-0.96) but did not reduce stroke (RR = 0.92, 95%CI = 0.54-1.58) and major cardiovascular events (MACE) (RR = 0.81, 95%CI = 0.65-1.02) risk. Sensitivity analysis results were stable. Safety was similar to the placebo group but had frequent injection-site reactions (RR = 6.56, 95%CI = 3.83-11.25), which were predominantly mild or moderate. A descriptive analysis of one RCT (ORION-5) was conducted due to different study designs, and suggested that inclisiran might be given semiannually from the beginning. Conclusion: Inclisiran is not beneficial for stroke or MACE prevention in ASCVD or patients at high risk of ASCVD but is associated with the reduction of MI. Given the limited number and quality of the available studies and the lack of a standardized definition for cardiovascular events, further studies are essential for confirming the results.
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]To compare the efficacy, safety and tolerability of valsartan to an angiotensin-converting enzyme (ACE) inhibitor, lisinopril, and placebo in patients with mild-to-moderate essential hypertension.
The pharmacological potency of various AT(1) antagonists assessed by Schild regression technique in man. [2018]A quantitative technique was used to compare the pharmacological potency in healthy volunteers of angiotensin II receptor antagonists (AIIA): candesartan cilexetil, losartan, irbesartan, valsartan, and telmisartan.
Hemodynamic and hormonal effects of quinaprilat in patients with congestive heart failure. [2014]To assess the pharmacodynamic activity and safety of rising single and multiple doses of intravenous quinaprilat compared with placebo in patients with New York Heart Association (NYHA) class III and IV congestive heart failure who were receiving digitalis or diuretic therapy or both.
Comparative trials in registration files of cardiovascular drugs: comparator drugs and dosing schemes. [2019]Registration files of 13 cardiovascular drugs were analysed with respect to the number of double-blind phase-III clinical trials, the use of placebo and active comparator drugs and their dosing schemes. Half of the 146 double-blind trials used active comparator drugs. The majority of files included first-choice reference drugs, but we also found trials in three files with lower dosing schemes of comparator drugs and four files which included only placebo or active controlled double-blind trials. To allow a better interpretation of the information provided in European Public Assessment Reports, which are published for every product approved for marketing in the European Union, uniform reporting is recommended on basic details of trial design, such as comparator drugs used and dosing schemes.
Cardiovascular safety of celecoxib in rheumatoid arthritis and osteoarthritis patients: A systematic review and meta-analysis. [2022]To assess the cardiovascular safety of celecoxib compared to non-selective non-steroid anti-inflammatory drugs or placebo.
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]Selective cyclooxygenase 2 (COX2) inhibitors (COXIBs) are effective anti-inflammatory and analgesic drugs with improved gastrointestinal (GI) safety compared to nonselective nonsteroidal anti-inflammatory drugs known as traditional (tNSAIDs). However, their use is associated with a cardiovascular (CV) hazard (i.e. increased incidence of thrombotic events and hypertension) due to the inhibition of COX2-dependent vascular prostacyclin. Aiming to design COX2-selective inhibitors with improved CV safety, new NO-releasing COXIBs (NO-COXIBs) have been developed. In these hybrid drugs, the NO-mediated CV effects are expected to compensate for the COXIB-mediated inhibition of prostacyclin. This study evaluates the potential CV beneficial effects of VA694, a promising NO-COXIB, the anti-inflammatory effects of which have been previously characterized in several in vitro and in vivo experimental models. When incubated in hepatic homogenate, VA694 acted as a slow NO-donor. Moreover, it caused NO-mediated relaxant effects in the vascular smooth muscle. The chronic oral administration of VA694 to young spontaneously hypertensive rats (SHRs) significantly slowed down the age-related development of hypertension and was associated with increased plasma levels of nitrates, stable end-metabolites of NO. Furthermore, a significant improvement of coronary flow and a significant reduction of endothelial dysfunction were observed in SHRs submitted to chronic administration of VA694. In conclusion, VA694 is a promising COX2-inhibiting hybrid drug, showing NO releasing properties which may mitigate the CV deleterious effects associated with the COX2-inhibition.
Are prescribers not aware of cardiovascular contraindications for diclofenac? A claims data analysis. [2020]To compare diclofenac use before and after implementation of European risk minimization measures in 2013, focusing on diclofenac initiators and prevalence of congestive heart failure (NYHA class II-IV), ischaemic heart disease, peripheral arterial disease and cerebrovascular disease (new contraindications) in these patients in Germany.
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]Selective cyclooxygenase-2 inhibitors and conventional non-selective non-steroidal anti-inflammatory drugs (nsNSAIDs) have been associated with adverse cardiovascular (CV) effects. We compared the CV safety of switching to celecoxib vs. continuing nsNSAID therapy in a European setting.
Parecoxib sodium demonstrates gastrointestinal safety comparable to placebo in healthy subjects. [2019]The gastrointestinal safety of the novel injectable cyclooxygenase-2 selective inhibitor, parecoxib sodium, was compared with the nonselective nonsteroidal anti-inflammatory drug, ketorolac, and placebo in healthy subjects.
Efficacy and safety evaluation of perindopril-lercanidipine combined therapy in patients with mild essential hypertension. [2019]To investigate the efficacy and safety of perindopril-lercanidipine combination versus perindopril or lercanidipine monotherapies in patients with mild essential hypertension.
Regression of left ventricular hypertrophy in hypertensive patients treated with indapamide SR 1.5 mg versus enalapril 20 mg: the LIVE study. [2019]To compare the efficacy of indapamide sustained release (SR) 1.5 mg and enalapril 20 mg at reducing left ventricular mass index (LVMI) in hypertensive patients with left ventricular hypertrophy (LVH).
Lercanidipine hydrochloride versus felodipine sustained-release for mild-to-moderate hypertension: a multi-center, randomized clinical trial. [2018]Lercanidipine hydrochloride and felodipine sustained-release tablets comparison for the treatment of patients with mild-to-moderate primary hypertension.
Sodium Tanshinone II A Sulfonate Injection as Adjuvant Treatment for Unstable Angina Pectoris: A Meta-Analysis of 17 Randomized Controlled Trials. [2022]To systematically evaluate the effectiveness and safety of Sodium Tanshinone II A Sulfonate Injection (STS) as one adjuvant therapy for treating unstable angina pectoris (UAP).