This trial is evaluating whether Inclisiran Sodium will improve 5 primary outcomes, 6 secondary outcomes, and 1 other outcome in patients with Hypercholesterolemia. Measurement will happen over the course of Baseline, Day 1080.
This trial requires 3275 total participants across 2 different treatment groups
This trial involves 2 different treatments. Inclisiran Sodium is the primary treatment being studied. Participants will all receive the same treatment. There is no placebo group. The treatments being tested are in Phase 3 and have had some early promising results.
The lifetime risk of having this condition is 20.5% for men and 23.7% for women. The lifetime risk of developing heart disease is greater than 10% in both sexes.
Symptoms of the condition can be mild and easily overlooked. Hypercholesterolemia may become a serious problem as people get older. It can take time before symptoms are noticed and treatment can be started. Treatment options include weight control programmes on diet and exercise alone or combination of diet and medication. Hypercholesterolemia can be detected during screening tests before the condition progresses to heart disease.
These experiments revealed that the treatment with statins was beneficial to correct the dyslipidemia in this animal model of hypercholesterolemia. Data from a recent study shows that hypercholesterolemia affects lipid handling through a complex mechanism involving the regulation of genes controlling lipid catabolism and genes controlling lipid synthesis.
Chronic (prolonged) hypercholesterolemia is not necessarily a curable disease but can be effectively controlled with appropriate therapy (e.g., statins, lifestyle modification, exercise, bariatric surgery, or weight loss) if patient readiness is obtained and motivation is maintained.
Hypercholesterolemia is defined by the National Cholesterol Education Program as a total serum cholesterol level ≥ 200mg/dl (5.55 mmol/L) in men or ≥ 200mg/dl in women. It is estimated that 10 to 20% of men and 12%-24% of women have hypercholesterolemia. Although the exact cause is unknown, elevated production of cholesterol by the liver and/or other organs, and/or defects in its uptake or metabolism, along with low levels of high-density lipoprotein or other apolipoprotein particles, likely play a role.
Hypercholesterolemia is commonly treated with lip- and statin-based prescription drug therapy, particularly statins such as atorvastatin or rosuvastatin. Also, dietary modification with low-fat diets supplemented with plant sterols for cholesterol lowering has been shown to reduce cholesterol levels, whereas fibrate medications are recommended only for those with very high cholesterol levels.
Inclisiran sodium, an oral agent for the treatment of hypercholesterolemia, reduces LDL-cholesterol by 37% in adults. Its efficacy decreases with increasing age. The tolerability of inhalation-based inhalation formulations is promising, with minimal impact on QTc interval. Further study is required to confirm that inhaled agents are no more safety risks than oral agents.
Results from a recent paper demonstrates that the use of Inclisiran sodium is more effective than a placebo, for the lowering of LDL cholesterol and TC. However, no difference in the effect on HDL cholesterol was found.
Almost all patients reported headache and dizziness as the most common side effects. The common side effects of inclisiran sodium are as follows: dizziness, fatigue, and an itch. All of these are manageable with drug tapering.
These data should not be used to determine at what age people should be screened for [hypercholesterolemia], because screening at 75 to 85 was associated with a 0.33 and 0.40 % prevalence of [high-density lipoprotein cholesterol]<35, 90 and 95 mg/dL in men and women, respectively. As people age, screening for [low-density lipoprotein cholesterol]<55 mg/dL will be more cost effective and may prevent unnecessary treatment and the associated costs.
Families with a single affected member are similar at the level of lipid profile to families with an affected member and of similar phenotype and age, suggesting a multifactorial determinants of the lipid phenotype. Thus cholesterol levels are likely multifactorial, which should be expected as part of the natural history of this disease.
There are a long list of treatments that offer hope to many patients with cholesterol problems; the list is never-ending. Although many of these treatments are not effective, one does stand out as the best-performing study of all: The pioglitazone [brand name Actos] study of patients with hypercholesterolemia. Since 2002, patients randomized to this drug regimen showed improvements on each of the major clinical outcomes studied. [Power(https://www.withpower.com/d/hypercholesterolemia-trials) offers a powerful resource to locate more recent studies on lipid-lowering treatment for patients with hypercholesterolemia.